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Sample records for adult mouse skin

  1. Histology and Ultrastructure of Transitional Changes in Skin Morphology in the Juvenile and Adult Four-Striped Mouse (Rhabdomys pumilio)

    OpenAIRE

    Eranée Stewart; Moyosore Salihu Ajao; Amadi Ogonda Ihunwo

    2013-01-01

    The four-striped mouse has a grey to brown coloured coat with four characteristic dark stripes interspersed with three lighter stripes running along its back. The histological differences in the skin of the juvenile and adult mouse were investigated by Haematoxylin and Eosin and Masson Trichrome staining, while melanocytes in the skin were studied through melanin-specific Ferro-ferricyanide staining. The ultrastructure of the juvenile skin, hair follicles, and melanocytes was also explored. I...

  2. Histology and Ultrastructure of Transitional Changes in Skin Morphology in the Juvenile and Adult Four-Striped Mouse (Rhabdomys pumilio

    Directory of Open Access Journals (Sweden)

    Eranée Stewart

    2013-01-01

    Full Text Available The four-striped mouse has a grey to brown coloured coat with four characteristic dark stripes interspersed with three lighter stripes running along its back. The histological differences in the skin of the juvenile and adult mouse were investigated by Haematoxylin and Eosin and Masson Trichrome staining, while melanocytes in the skin were studied through melanin-specific Ferro-ferricyanide staining. The ultrastructure of the juvenile skin, hair follicles, and melanocytes was also explored. In both the juvenile and adult four-striped mouse, pigment-containing cells were observed in the dermis and were homogeneously dispersed throughout this layer. Apart from these cells, the histology of the skin of the adult four-striped mouse was similar to normal mammalian skin. In the juvenile four-striped mouse, abundant hair follicles of varying sizes were observed in the dermis and hypodermis, while hair follicles of similar size were only present in the dermis of adult four-striped mouse. Ultrastructural analysis of juvenile hair follicles revealed that the arrangement and differentiation of cellular layers were typical of a mammal. This study therefore provides unique transition pattern in the four-striped mouse skin morphology different from the textbook description of the normal mammalian skin.

  3. Hyperelastic Material Properties of Mouse Skin under Compression.

    Directory of Open Access Journals (Sweden)

    Yuxiang Wang

    Full Text Available The skin is a dynamic organ whose complex material properties are capable of withstanding continuous mechanical stress while accommodating insults and organism growth. Moreover, synchronized hair cycles, comprising waves of hair growth, regression and rest, are accompanied by dramatic fluctuations in skin thickness in mice. Whether such structural changes alter skin mechanics is unknown. Mouse models are extensively used to study skin biology and pathophysiology, including aging, UV-induced skin damage and somatosensory signaling. As the skin serves a pivotal role in the transfer function from sensory stimuli to neuronal signaling, we sought to define the mechanical properties of mouse skin over a range of normal physiological states. Skin thickness, stiffness and modulus were quantitatively surveyed in adult, female mice (Mus musculus. These measures were analyzed under uniaxial compression, which is relevant for touch reception and compression injuries, rather than tension, which is typically used to analyze skin mechanics. Compression tests were performed with 105 full-thickness, freshly isolated specimens from the hairy skin of the hind limb. Physiological variables included body weight, hair-cycle stage, maturity level, skin site and individual animal differences. Skin thickness and stiffness were dominated by hair-cycle stage at young (6-10 weeks and intermediate (13-19 weeks adult ages but by body weight in mature mice (26-34 weeks. Interestingly, stiffness varied inversely with thickness so that hyperelastic modulus was consistent across hair-cycle stages and body weights. By contrast, the mechanics of hairy skin differs markedly with anatomical location. In particular, skin containing fascial structures such as nerves and blood vessels showed significantly greater modulus than adjacent sites. Collectively, this systematic survey indicates that, although its structure changes dramatically throughout adult life, mouse skin at a given

  4. Multistage chemical carcinogenesis in mouse skin

    Energy Technology Data Exchange (ETDEWEB)

    Slaga, T.J.; Fischer, S.M.; Weeks, C.E.; Klein-Szanto, A.J.P.

    1979-01-01

    Skin tumors in mice can be induced by the sequential application of a subthreshold dose of a carcinogen (initiation phase) followed by repetitive treatment with a noncarcinogenic tumor promoter. The initiation phase requires only a single application of either a direct acting carcinogen or a procarcinogen which has to be metabolized before being active and is essentially an irreversible step which probably involves a somatic cell mutation. There is a good correlation between the skin tumor initiating activites of several polycyclic aromatic hydrocarbons (PAH) and their ability to bind covalently to epidermal DNA. Laboratory results suggest that bay region diol-epoxides are the ultimate carcinogenic form of PAH carcinogens. Potent inhibitors and stimulators of PAH tumor initiation appear to affect the level of the PAH diol-epoxide reacting with specific DNA bases. Reecent data suggests that the tumor promotion stage involves at least three important steps: (1) the induction of embryonic looking cells (dark cells) in adult epidermis; (2) an increased production of epidermal prostaglandins and polyamines; (3) sustained proliferation of dark cells. Retinoic acid specifically inhibits step two whereas the anti-inflammatory steriod fluocinolone acetonide is a potent inhibitor of steps one and three. The mechanism and the importance of a specific sequence for each step in chemical carcinogenesis in mouse skin are detailed.

  5. Comparison between human fetal and adult skin

    OpenAIRE

    Coolen, N.A.; Schouten, K.C.; Middelkoop, E.; Ulrich, M.

    2009-01-01

    Healing of early-gestation fetal wounds results in scarless healing. Since the capacity for regeneration is probably inherent to the fetal skin itself, knowledge of the fetal skin composition may contribute to the understanding of fetal wound healing. The aim of this study was to analyze the expression profiles of different epidermal and dermal components in the human fetal and adult skin. In the human fetal skin (ranging from 13 to 22 weeks’ gestation) and adult skin biopsies, the expression...

  6. Collagen Content in Skin and Internal Organs of the Tight Skin Mouse: An Animal Model of Scleroderma

    OpenAIRE

    Jayanthi Manne; Marina Markova; Siracusa, Linda D.; Jimenez, Sergio A.

    2013-01-01

    The Tight Skin mouse is a genetically induced animal model of tissue fibrosis caused by a large in-frame mutation in the gene encoding fibrillin-1 (Fbn-1). We examined the influence of gender on the collagen content of tissues in C57BL/6J wild type (+/+) and mutant Tight Skin (Tsk/+) mice employing hydroxyproline assays. Tissue sections were stained with Masson’s trichrome to identify collagen in situ. Adult Tsk/+ mice skin contains ~15% more collagen, on average, than skin from +/+ mice of t...

  7. Expression of naked DNA in human, pig, and mouse skin.

    OpenAIRE

    Hengge, U R; Walker, P. S.; Vogel, J. C.

    1996-01-01

    The insertion and expression of genes in the epidermis may have a variety of therapeutic uses, including the treatment of skin diseases. Here we show that when both human skin organ cultures and human skin grafts on immunocompromised mice are injected with naked DNA, the DNA is taken-up and genes are expressed in the epidermis in a manner similar to both pig skin injected in vivo and injected pig skin organ cultures. In contrast, DNA injected into mouse skin is expressed not just in the epide...

  8. Metabolism of skin-absorbed resveratrol into its glucuronized form in mouse skin.

    Science.gov (United States)

    Murakami, Itsuo; Chaleckis, Romanas; Pluskal, Tomáš; Ito, Ken; Hori, Kousuke; Ebe, Masahiro; Yanagida, Mitsuhiro; Kondoh, Hiroshi

    2014-01-01

    Resveratrol (RESV) is a plant polyphenol, which is thought to have beneficial metabolic effects in laboratory animals as well as in humans. Following oral administration, RESV is immediately catabolized, resulting in low bioavailability. This study compared RESV metabolites and their tissue distribution after oral uptake and skin absorption. Metabolomic analysis of various mouse tissues revealed that RESV can be absorbed and metabolized through skin. We detected sulfated and glucuronidated RESV metabolites, as well as dihydroresveratrol. These metabolites are thought to have lower pharmacological activity than RESV. Similar quantities of most RESV metabolites were observed 4 h after oral or skin administration, except that glucuronidated RESV metabolites were more abundant in skin after topical RESV application than after oral administration. This result is consistent with our finding of glucuronidated RESV metabolites in cultured skin cells. RESV applied to mouse ears significantly suppressed inflammation in the TPA inflammation model. The skin absorption route could be a complementary, potent way to achieve therapeutic effects with RESV.

  9. [Staphylococcal scalded skin syndrome in adults].

    Science.gov (United States)

    Mikkelsen, Carsten Sauer; Mikkelsen, Dorthe Bisgaard; Jensen, Thøger Gorm; Vestergaard, Vibeke

    2010-03-01

    We describe a case of adult staphylococcal scalded skin syndrome (SSSS) in a 91-year-old woman. The patient had a Staphylococcus aureus infection in her right ear with redness and yellow secretion. A few days later she developed Nikolsky sign-positive tender enlarged flaccid bullae involving most parts of her body. The bullae ruptured easily and left a erythematous base. The histopathological changes were characteristic for adult SSSS. The patient was well-treated with intravenous dicloxacillin, topical antibiotic and antiseptic treatment. The patient had marked thrombocytosis, but no interest in further examination. PMID:20199754

  10. Calcium Glucarate Prevents Tumor Formation in Mouse Skin

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Objective Calcium Glucarate (Cag), Ca salt of D-glucaric acid is a naturally occurring non-toxic compound present in fruits, vegetables and seeds of some plants, and suppress tumor growth in different models. Due to lack of knowledge about its mode of action its uses are limited in cancer chemotherapy thus the objective of the study was to study the mechanism of action of Cag on mouse skin tumorigenesis. Methods We have estimated effect of Cag on DMBA induced mouse skin tumor development following complete carcinogenesis protocol. We measured, epidermal transglutaminase activity (TG), a marker of cell differentiation after DMBA and/or Cag treatment and [3H] thymidine incorporation into DNA as a marker for cell proliferation. Results Topical application of Cag suppressed the DMBA induced mouse skin tumor development. Topical application of Cag significantly modifies the critical events of proliferation and differentiation TG activity was found to be reduced after DMBA treatment. Reduction of the TG activity was dependent on the dose of DMBA and duration of DMBA exposure. Topical application of Cag significantly alleviated DMBA induced inhibition of TG. DMBA also caused stimulation of DNA synthesis in epidermis, which was inhibited by Cag. Conclusion Cag inhibits DMBA induced mouse skin tumor development. Since stimulation of DNA synthesis reflects proliferation and induction of TG represents differentiation, the antitumorigenic effect of Cag is considered to be possibly due to stimulation of differentiation and suppression of proliferation.

  11. Excoriation (skin-picking) disorder in adults

    DEFF Research Database (Denmark)

    Leibovici, Vera; Koran, Lorrin M; Murad, Sari;

    2015-01-01

    was more prevalent in the SPD-positive Jewish subsample (p=0.02). In the total sample, diabetes mellitus was more common in women than in men (p=0.04). CONCLUSION: Lifetime SPD appears to be relatively common in Israeli adults and associated with other mental disorders. Differences in the self......OBJECTIVE: We sought to estimate the lifetime prevalence of Excoriation (Skin-Picking) Disorder (SPD) in the Israeli adult population as a whole and compare SPD prevalence in the Jewish and Arab communities. We also explored demographic, medical and psychological correlates of SPD diagnosis....... METHODS: Questionnaires and scales screening for SPD, and assessing the severity of perceived stress, depression, obsessive-compulsive disorder (OCD), body dysmorphic disorder (BDD), alcohol use, illicit drug use, and medical disorders were completed in a sample of 2145 adults attending medical settings...

  12. Collagen Content in Skin and Internal Organs of the Tight Skin Mouse: An Animal Model of Scleroderma

    Directory of Open Access Journals (Sweden)

    Jayanthi Manne

    2013-01-01

    Full Text Available The Tight Skin mouse is a genetically induced animal model of tissue fibrosis caused by a large in-frame mutation in the gene encoding fibrillin-1 (Fbn-1. We examined the influence of gender on the collagen content of tissues in C57BL/6J wild type (+/+ and mutant Tight Skin (Tsk/+ mice employing hydroxyproline assays. Tissue sections were stained with Masson’s trichrome to identify collagen in situ. Adult Tsk/+ mice skin contains ~15% more collagen, on average, than skin from +/+ mice of the same gender. The heart of Tsk/+ males had significantly more collagen than that of +/+ males. No significant gender differences were found in lungs and kidney collagen content. Overall, the collagen content of Tsk/+ males and +/+ males was higher than that of their Tsk/+ and +/+ female counterparts, respectively. Our data confirm increased deposition of collagen in skin and hearts of Tsk/+ mice; however, the effects of the Tsk mutation on collagen content are both tissue specific and gender specific. These results indicate that comparative studies of collagen content between normal and Tsk/+ mice skin and internal organs must take into account gender differences caused by expression of the androgen receptor.

  13. Primary monolayer culture of adult mouse hepatocytes

    International Nuclear Information System (INIS)

    Primary monolayer cultures of adult mouse hepatocytes isolated by collagenase perfusion of the liver in situ were exposed to 2 hepatotropic viruses, an avian influenza A virus adapted to grow in mouse liver in vivo and a herpes simplex type I virus. Influenza virus infection led to lysis of individual hepatocytes and total monolayer destruction within 18 to 120 hours after infection according to the virus dose used. Virus replication was evidenced by assaying hepatocyte supernates for hemagglutinin and infectivity, immunofluorescent staining and by electron microscopy. Herpes virus infection resulted in polykaryocyte formation followed by nuclear pycnosis and cell lysis. Virus replication was assayed by titration of supernate infectivity. (auth.)

  14. Methodology for statistical analysis of SENCAR mouse skin assay data.

    OpenAIRE

    Stober, J A

    1986-01-01

    Various response measures and statistical methods appropriate for the analysis of data collected in the SENCAR mouse skin assay are examined. The characteristics of the tumor response data do not readily lend themselves to the classical methods for hypothesis testing. The advantages and limitations of conventional methods of analysis and methods recommended in the literature are discussed. Several alternative response measures that were developed specifically to answer the problems inherent i...

  15. Metabolism of skin-absorbed resveratrol into its glucuronized form in mouse skin.

    Directory of Open Access Journals (Sweden)

    Itsuo Murakami

    Full Text Available Resveratrol (RESV is a plant polyphenol, which is thought to have beneficial metabolic effects in laboratory animals as well as in humans. Following oral administration, RESV is immediately catabolized, resulting in low bioavailability. This study compared RESV metabolites and their tissue distribution after oral uptake and skin absorption. Metabolomic analysis of various mouse tissues revealed that RESV can be absorbed and metabolized through skin. We detected sulfated and glucuronidated RESV metabolites, as well as dihydroresveratrol. These metabolites are thought to have lower pharmacological activity than RESV. Similar quantities of most RESV metabolites were observed 4 h after oral or skin administration, except that glucuronidated RESV metabolites were more abundant in skin after topical RESV application than after oral administration. This result is consistent with our finding of glucuronidated RESV metabolites in cultured skin cells. RESV applied to mouse ears significantly suppressed inflammation in the TPA inflammation model. The skin absorption route could be a complementary, potent way to achieve therapeutic effects with RESV.

  16. Multiple skin tumors of indeterminate cells in an adult.

    Science.gov (United States)

    Kolde, G; Bröcker, E B

    1986-10-01

    An adult patient with multiple unusual histiocytic tumors of the skin is described. As shown by immunohistologic study, electron microscopy, and immunoelectron microscopy, the tumors represent circumscribed proliferations of the Langerhans cell-related indeterminate dendritic cells of the skin. This distinct cutaneous histiocytosis may represent a paraneoplastic syndrome.

  17. Mouse skin damages caused by fractionated irradiation with carbon ions

    Energy Technology Data Exchange (ETDEWEB)

    Ando, K.; Chen, Y.J.; Ohira, C.; Nojima, K.; Ando, S.; Kobayashi, N.; Ohbuchi, T.; Shimizu, W. [Space and Particle Radiation Science Research Group, Chiba (Japan); Koike, S.; Kanai, T. [National Inst. of Radiological Sciences, Chiba (Japan). Div. of Accelerator Physics

    1997-09-01

    We have investigated carbon-dose responses of early and late skin damages after daily fractionations to the mouse leg. Depilated legs were irradiated with 7 different positions within 290 MeV/u carbon beams. Fractionation schedules were 1, 2, 4 and 8 daily fractions. Skin reaction was scored every other day for 32 days. Five highest scores in individual mice were averaged, and used as averaged peak reaction. The isoeffect doses to produce an averaged peak skin reaction of 3.0 (moist desquamation) on dose-response curves were calculated with 95% confidence limit. The isoeffect dose for control gamma rays constantly increased with an increase in the number of fraction. The isoeffect doses in low LET carbon ions of 14- and 20 keV/{mu}m also increased up to 4 fractions, but did not increase when 4 fractions increased to 8 fractions. The saturation of isoeffect dose was more prominently observed for 40 keV/{mu}m in such that the isoeffect doses did not change among 2, 4 and 8 fractions. The isoeffect doses for LET higher than 50 keV/{mu}m were smaller than those for lower LET. However, the isoeffect doses for 50-, 60-, 80- and 100 keV/{mu} steadily increased with an increase in the number of fraction and did not show any saturation up to 8 fractions. Relation between LET and RBE was linear for all fractionation schedules. The slope of regression line in 4 fractions was steepest, and significantly (P<0.05) different from that in 1 fraction. (orig.)

  18. Mouse Genetic Models Reveal Surprising Functions of IκB Kinase Alpha in Skin Development and Skin Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Xia, Xiaojun [The Methodist Hospital Research Institute, Houston, TX 77030 (United States); Park, Eunmi [Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115 (United States); Fischer, Susan M. [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX 78967 (United States); Hu, Yinling, E-mail: huy2@mail.nih.gov [Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21701 (United States)

    2013-02-15

    Gene knockout studies unexpectedly reveal a pivotal role for IκB kinase alpha (IKKα) in mouse embryonic skin development. Skin carcinogenesis experiments show that Ikkα heterozygous mice are highly susceptible to chemical carcinogen or ultraviolet B light (UVB) induced benign and malignant skin tumors in comparison to wild-type mice. IKKα deletion mediated by keratin 5 (K5).Cre or K15.Cre in keratinocytes induces epidermal hyperplasia and spontaneous skin squamous cell carcinomas (SCCs) in Ikkα floxed mice. On the other hand, transgenic mice overexpressing IKKα in the epidermis, under the control of a truncated loricrin promoter or K5 promoter, develop normal skin and show no defects in the formation of the epidermis and other epithelial organs, and the transgenic IKKα represses chemical carcinogen or UVB induced skin carcinogenesis. Moreover, IKKα deletion mediated by a mutation, which generates a stop codon in the Ikkα gene, has been reported in a human autosomal recessive lethal syndrome. Downregulated IKKα and Ikkα mutations and deletions are found in human skin SCCs. The collective evidence not only highlights the importance of IKKα in skin development, maintaining skin homeostasis, and preventing skin carcinogenesis, but also demonstrates that mouse models are extremely valuable tools for revealing the mechanisms underlying these biological events, leading our studies from bench side to bedside.

  19. Cell proliferation and neurogenesis in adult mouse brain.

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    Olivia L Bordiuk

    Full Text Available Neurogenesis, the formation of new neurons, can be observed in the adult brain of many mammalian species, including humans. Despite significant progress in our understanding of adult neurogenesis, we are still missing data about the extent and location of production of neural precursors in the adult mammalian brain. We used 5-ethynyl-2'-deoxyuridine (EdU to map the location of proliferating cells throughout the entire adult mouse brain and found that neurogenesis occurs at two locations in the mouse brain. The larger one we define as the main proliferative zone (MPZ, and the smaller one corresponds to the subgranular zone of the hippocampus. The MPZ can be divided into three parts. The caudate migratory stream (CMS occupies the middle part of the MPZ. The cable of proliferating cells emanating from the most anterior part of the CMS toward the olfactory bulbs forms the rostral migratory stream. The thin layer of proliferating cells extending posteriorly from the CMS forms the midlayer. We have not found any additional aggregations of proliferating cells in the adult mouse brain that could suggest the existence of other major neurogenic zones in the adult mouse brain.

  20. Histochemical Localization of Glutathione Dependent NBT-Reductase in Mouse Skin

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective Localization of the glutathione dependent Nitroblue tetrazolium (NBT) reductase in fresh frozen sections of mouse skin and possible dependence of NBT reductase on tissue thiol levels has been investigated. Methods The fresh frozen tissue sections (8m thickness) were prepared and incubated in medium containing NBT, reduced glutathione (GSH) and phosphate buffer. The staining for GSH was performed with mercury orange. Results  The activity of the NBT-reductase in mouse skin has been found to be localized in the areas rich in glutathione and actively proliferating area of the skin. Conclusion The activity of the NBT-reductase seems to be dependent on the glutathione contents.

  1. Matrine inhibits proliferation of mouse skin fibroblasts induced by platelet-derived growth factor-BB

    Institute of Scientific and Technical Information of China (English)

    WU Yan-an; GAO Chun-fang; WANG Hao; HUANG Chao; KONG Xian-tao

    2001-01-01

    To study the effect of matrine on proliferation of mouse skin fibroblasts induced by platelet-derived growth factor-BB (PDGF-BB). Methods: Mouse skin fibroblasts were obtained from newborn ⅠCR mice and propagated in vitro. Proliferation of cell was analyzed by mitochondrial reduction of tetrazolium salt MTT and actual cell count. Results: Matrine (50 to 500 μg/ml) caused dose-dependent reduction of serum-stimulated cell growth. Growth inhibition was totally reversed after removal of the drug. Matrine also inhibited PDGF-BB induced cell growth dose-dependently. Conclusion: Matrine exhibits potent anti-proliferation effect on mouse skin fibroblast. This effect appears to be mediated by decrease of PDGF-induced growth. These results suggest that matrine might have preventive and therapeutic implication in skin fibrosis.

  2. Profiling of Sox4-dependent transcriptome in skin links tumour suppression and adult stem cell activation

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    Miguel Foronda

    2015-12-01

    Full Text Available Adult stem cells (ASCs reside in specific niches in a quiescent state in adult mammals. Upon specific cues they become activated and respond by self-renewing and differentiating into newly generated specialised cells that ensure appropriate tissue fitness. ASC quiescence also serves as a tumour suppression mechanism by hampering cellular transformation and expansion (White AC et al., 2014. Some genes restricted to early embryonic development and adult stem cell niches are often potent modulators of stem cell quiescence, and derailed expression of these is commonly associated to cancer (Vervoort SJ et al., 2013. Among them, it has been shown that recommissioned Sox4 expression facilitates proliferation, survival and migration of malignant cells. By generating a conditional Knockout mouse model in stratified epithelia (Sox4cKO mice, we demonstrated a delayed plucking-induced Anagen in the absence of Sox4. Skin global transcriptome analysis revealed a prominent defect in the induction of transcriptional networks that control hair follicle stem cell (HFSC activation such as those regulated by Wnt/Ctnnb1, Shh, Myc or Sox9, cell cycle and DNA damage response-associated pathways. Besides, Sox4cKO mice are resistant to skin carcinogenesis, thus linking Sox4 to both normal and pathological HFSC activation (Foronda M et al., 2014. Here we provide additional details on the analysis of Sox4-regulated transcriptome in Telogen and Anagen skin. The raw and processed microarray data is deposited in GEO under GSE58155.

  3. Histomorphological Phenotyping of the Adult Mouse Brain.

    Science.gov (United States)

    Mikhaleva, Anna; Kannan, Meghna; Wagner, Christel; Yalcin, Binnaz

    2016-01-01

    This article describes a series of standard operating procedures for morphological phenotyping of the mouse brain using basic histology. Many histological studies of the mouse brain use qualitative approaches based on what the human eye can detect. Consequently, some phenotypic information may be missed. Here we describe a quantitative approach for the assessment of brain morphology that is simple and robust. A total of 78 measurements are made throughout the brain at specific and well-defined regions, including the cortex, the hippocampus, and the cerebellum. Experimental design and timeline considerations, including strain background effects, the importance of sectioning quality, measurement variability, and efforts to correct human errors are discussed. © 2016 by John Wiley & Sons, Inc. PMID:27584555

  4. Expression and Function of Group IIE Phospholipase A2 in Mouse Skin.

    Science.gov (United States)

    Yamamoto, Kei; Miki, Yoshimi; Sato, Hiroyasu; Nishito, Yasumasa; Gelb, Michael H; Taketomi, Yoshitaka; Murakami, Makoto

    2016-07-22

    Recent studies using knock-out mice for various secreted phospholipase A2 (sPLA2) isoforms have revealed their non-redundant roles in diverse biological events. In the skin, group IIF sPLA2 (sPLA2-IIF), an "epidermal sPLA2" expressed in the suprabasal keratinocytes, plays a fundamental role in epidermal-hyperplasic diseases such as psoriasis and skin cancer. In this study, we found that group IIE sPLA2 (sPLA2-IIE) was expressed abundantly in hair follicles and to a lesser extent in basal epidermal keratinocytes in mouse skin. Mice lacking sPLA2-IIE exhibited skin abnormalities distinct from those in mice lacking sPLA2-IIF, with perturbation of hair follicle ultrastructure, modest changes in the steady-state expression of a subset of skin genes, and no changes in the features of psoriasis or contact dermatitis. Lipidomics analysis revealed that sPLA2-IIE and -IIF were coupled with distinct lipid pathways in the skin. Overall, two skin sPLA2s, hair follicular sPLA2-IIE and epidermal sPLA2-IIF, play non-redundant roles in distinct compartments of mouse skin, underscoring the functional diversity of multiple sPLA2s in the coordinated regulation of skin homeostasis and diseases. PMID:27226633

  5. A Comprehensive Atlas of the Adult Mouse Penis.

    Science.gov (United States)

    Phillips, Tiffany R; Wright, David K; Gradie, Paul E; Johnston, Leigh A; Pask, Andrew J

    2015-01-01

    Mice are routinely used to study the development of the external genitalia and, in particular, the process of male urethral closure. This is because misplacement of the male penile urethra, or hypospadias, is amongst the most common birth defects reported in humans. While mice present a tractable model to study penile development, several structures differ between mice and humans, and there is a lack of consensus in the literature on their annotation and developmental origins. Defining the ontology of the mouse prepuce is especially important for the relevance and interpretation of mouse models of hypospadias to human conditions. We have developed a detailed annotation of the adult mouse penis that addresses these differences and enables an accurate comparison of murine and human hypospadias phenotypes. Through MRI data, gross morphology and section histology, we define the origin of the mouse external and internal prepuces, their relationship to the single human foreskin as well as provide a comprehensive view of the various structures of the mouse penis and their associated muscle attachments within the body. These data are combined to annotate structures in a novel 3D adult penis atlas that can be downloaded, viewed at any angle, and manipulated to examine the relationship of various structures.

  6. Topical Application of Oleuropein Induces Anagen Hair Growth in Telogen Mouse Skin.

    Directory of Open Access Journals (Sweden)

    Tao Tong

    Full Text Available Oleuropein promoted cultured human follicle dermal papilla cell proliferation and induced LEF1 and Cyc-D1 mRNA expression and β-catenin protein expression in dermal papilla cells. Nuclear accumulation of β-catenin in dermal papilla cells was observed after oleuropein treatment. Topical application of oleuropein (0.4 mg/mouse/day to C57BL/6N mice accelerated the hair-growth induction and increased the size of hair follicles in telogenic mouse skin. The oleuropein-treated mouse skin showed substantial upregulation of Wnt10b, FZDR1, LRP5, LEF1, Cyc-D1, IGF-1, KGF, HGF, and VEGF mRNA expression and β-catenin protein expression.These results demonstrate that topical oleuroepin administration induced anagenic hair growth in telogenic C57BL/6N mouse skin. The hair-growth promoting effect of oleuropein in mice appeared to be associated with the stimulation of the Wnt10b/β-catenin signaling pathway and the upregulation of IGF-1, KGF, HGF, and VEGF gene expression in mouse skin tissue.

  7. Compression-induced HIF-1 enhances thrombosis and PAI-1 expression in mouse skin.

    Science.gov (United States)

    Kaneko, Maki; Minematsu, Takeo; Yoshida, Mikako; Nishijima, Yoshimi; Noguchi, Hiroshi; Ohta, Yasunori; Nakagami, Gojiro; Mori, Taketoshi; Sanada, Hiromi

    2015-09-01

    Pressure ulcers result from tissue hypoxia caused by external forces. Thrombosis due to external forces is considered important, and hypoxia inducible factor-1 (HIF-1) is a master regulator of pressure ulcer development. To date, however, their causal relationship has not been determined. This study therefore investigated the mutual relationship between thrombosis and HIF-1 activation in compressed mouse skin, based on a hypothesis that HIF-1 regulation by plasminogen activator inhibitor-1 (PAI-1) enhances thrombosis. Compression of mouse skin significantly increased the numbers of thrombi and HIF-1α-positive cells compared with control skin. A thrombosis inhibitor significantly reduced the numbers of HIF-1α-positive cells and an HIF-1 inhibitor significantly inhibited thrombosis in compressed skin tissue, suggesting a mutual relationship between thrombosis and HIF-1 activation. Compression of mouse skin also enhanced the level of Pai-1 messenger RNA expression, but this increase was significantly reduced by treatment with an HIF-1 inhibitor, whereas a thrombosis inhibitor had no effect. These results suggested the involvement of PAI-1 in HIF-1-enhanced thrombosis and that an additional factor participates in regulating Pai-1 expression in compressed skin. These findings may suggest new strategies in pressure ulcer management.

  8. Skin tears: care and management of the older adult at home.

    Science.gov (United States)

    Holmes, Regina F; Davidson, Martha W; Thompson, Bonnie J; Kelechi, Teresa J

    2013-02-01

    Skin tears experienced by older adults require special skills to promote healing. Home healthcare providers are in key positions to manage skin tears and prevent further skin trauma. Several guidelines, risk assessments, classifications, and products exist to manage high-risk patients. Frequent evaluation of the effectiveness of the treatment and prevention strategies in an overall skin care protocol for home care patients is critical to reduce skin tear incidence and promote prompt healing when skin tears are present.

  9. Imaging the electric field associated with mouse and human skin wounds

    OpenAIRE

    Nuccitelli, Richard; Nuccitelli, Pamela; Ramlatchan, Samdeo; Sanger, Richard; Smith, Peter J.S.

    2008-01-01

    We have developed a noninvasive instrument called the bioelectric field imager (BFI) for mapping the electric field between the epidermis and the stratum corneum near wounds in both mouse and human skin. Rather than touching the skin, the BFI vibrates a small metal probe with a displacement of 180 μm in air above the skin to detect the surface potential of the epidermis through capacitative coupling. Here we describe our first application of the BFI measuring the electric field between the st...

  10. An anatomic gene expression atlas of the adult mouse brain

    OpenAIRE

    Ng, Lydia; Bernard, Amy; Lau, Chris; Overly, Caroline C.; Dong, Hong-Wei; Kuan, Chihchau; Pathak, Sayan; Sunkin, Susan M.; Dang, Chinh; Bohland, Jason W.; Bokil, Hemant; Mitra, Partha P.; Puelles, Luis; Hohmann, John; Anderson, David J.

    2009-01-01

    Studying gene expression provides a powerful means of understanding structure-function relationships in the nervous system. The availability of genome-scale in situ hybridization datasets enables new possibilities for understanding brain organization based on gene expression patterns. The Anatomic Gene Expression Atlas (AGEA) is a new relational atlas revealing the genetic architecture of the adult C57Bl/6J mouse brain based on spatial correlations across expression data for thousands of gene...

  11. The optical properties of mouse skin in the visible and near infrared spectral regions.

    Science.gov (United States)

    Sabino, Caetano P; Deana, Alessandro M; Yoshimura, Tania M; da Silva, Daniela F T; França, Cristiane M; Hamblin, Michael R; Ribeiro, Martha S

    2016-07-01

    Visible and near-infrared radiation is now widely employed in health science and technology. Pre-clinical trials are still essential to allow appropriate translation of optical methods into clinical practice. Our results stress the importance of considering the mouse strain and gender when planning pre-clinical experiments that depend on light-skin interactions. Here, we evaluated the optical properties of depilated albino and pigmented mouse skin using reproducible methods to determine parameters that have wide applicability in biomedical optics. Light penetration depth (δ), absorption (μa), reduced scattering (μ's) and reduced attenuation (μ't) coefficients were calculated using the Kubelka-Munk model of photon transport and spectrophotometric measurements. Within a broad wavelength coverage (400-1400nm), the main optical tissue interactions of visible and near infrared radiation could be inferred. Histological analysis was performed to correlate the findings with tissue composition and structure. Disperse melanin granules present in depilated pigmented mouse skin were shown to be irrelevant for light absorption. Gender mostly affected optical properties in the visible range due to variations in blood and abundance of dense connective tissue. On the other hand, mouse strains could produce more variations in the hydration level of skin, leading to changes in absorption in the infrared spectral region. A spectral region of minimal light attenuation, commonly referred as the "optical window", was observed between 600 and 1350nm.

  12. The optical properties of mouse skin in the visible and near infrared spectral regions.

    Science.gov (United States)

    Sabino, Caetano P; Deana, Alessandro M; Yoshimura, Tania M; da Silva, Daniela F T; França, Cristiane M; Hamblin, Michael R; Ribeiro, Martha S

    2016-07-01

    Visible and near-infrared radiation is now widely employed in health science and technology. Pre-clinical trials are still essential to allow appropriate translation of optical methods into clinical practice. Our results stress the importance of considering the mouse strain and gender when planning pre-clinical experiments that depend on light-skin interactions. Here, we evaluated the optical properties of depilated albino and pigmented mouse skin using reproducible methods to determine parameters that have wide applicability in biomedical optics. Light penetration depth (δ), absorption (μa), reduced scattering (μ's) and reduced attenuation (μ't) coefficients were calculated using the Kubelka-Munk model of photon transport and spectrophotometric measurements. Within a broad wavelength coverage (400-1400nm), the main optical tissue interactions of visible and near infrared radiation could be inferred. Histological analysis was performed to correlate the findings with tissue composition and structure. Disperse melanin granules present in depilated pigmented mouse skin were shown to be irrelevant for light absorption. Gender mostly affected optical properties in the visible range due to variations in blood and abundance of dense connective tissue. On the other hand, mouse strains could produce more variations in the hydration level of skin, leading to changes in absorption in the infrared spectral region. A spectral region of minimal light attenuation, commonly referred as the "optical window", was observed between 600 and 1350nm. PMID:27101274

  13. Histochemical Localization of Glutathione Dependent NBT—Reductase in Mouse Skin

    Institute of Scientific and Technical Information of China (English)

    YOESHWERSHUKLA

    2001-01-01

    Objective:Localization of the glutathione dependent Nitroblue tetrazolium(NBT) reductase in fresh frozen sections of mouse skin and possible dependence of NBT reductase on tissue thiol levels has been investigated.Methods:The fresh frozen tissue sections(8m thickness)were prepared and incuated in medium containing NBT,reduced glutathione(GSH) and Phosphate uffer,The staining for GSH was performed with mercury orange.Results:The activity of the NBT-reductase in mouse skin has een found to be localized in the areas rich in glutatione and actively proliferating area of the skin.Conclusion:The activity of the NBT-reductase seems to be dependent on the glutatione contents.

  14. Delayed tail loss during the invasion of mouse skin by cercariae of Schistosoma japonicum.

    Science.gov (United States)

    Wang, Ting; Fang, Zheng-Ming; Lei, Jia-Hui; Guan, Fei; Liu, Wen-Qi; Bartlett, Ann; Whitfield, Phil; Li, Yong-Long

    2012-02-01

    A traditional assumption is that schistosome cercariae lose their tails at the onset of penetration. It has, however, recently been demonstrated that, for Schistosoma mansoni, cercarial tails were not invariably being shed as penetration took place and a high proportion of tails entered human skin under experimental conditions. This phenomenon was termed delayed tail loss (DTL). In this paper, we report that DTL also happens with S. japonicum cercariae during penetration of mouse skin. It occurred at all cercarial densities tested, from as few as 10 cercariae/2·25 cm(2) of mouse skin up to 200 cercariae. Furthermore, it was demonstrated that there was a density-dependent increase in DTL as cercarial densities increased. No such density-dependent enhancement was shown for percentage attachment over the same cercarial density range.

  15. The biodisposition and hypertrichotic effects of bimatoprost in mouse skin.

    Science.gov (United States)

    Woodward, David F; Tang, Elaine S-H; Attar, Mayssa; Wang, Jenny W

    2013-02-01

    Studies on bimatoprost were performed with two objectives: (i) to determine whether bimatoprost possesses hair growth-stimulating properties beyond eyelash hypertrichosis and (ii) to investigate the biodisposition of bimatoprost in skin for the first time. Bimatoprost, at the dose used clinically for eyelash growth (0.03%) and given once daily for 14 days, increased pelage hair growth in C57/black 6 mice. This occurred as a much earlier onset of new hair growth in shaved mice and the time taken to achieve complete hair regrowth, according to photographic documentation and visual assessment. Bimatoprost biodisposition in the skin was determined at three concentrations: 0.01%, 0.03% and 0.06%. Dose-dependent C(max) values were obtained (3.41, 6.74, 12.3 μg/g tissue), and cutaneous bimatoprost was well maintained for 24 h following a single dose. Bimatoprost was recovered from the skin only as the intact molecule, with no detectable levels of metabolites. Thus, bimatoprost produces hypertrichosis as the intact molecule.

  16. The spleen and skin wound healing in Xenopus adults.

    Science.gov (United States)

    Franchini, Antonella; Della Rocca, Annalaura; Bertolotti, Evelina

    2016-07-01

    In most vertebrates, the regenerative capacity to restore lost/damage tissues to original structure and functionality decreases at some time during ontogenesis. To evaluate the role of the acquired immunity in the decline of regenerative potential, we examined the cellular responses elicited in the spleen during skin repair in Xenopus adults. Modifications in the architecture were found to be induced and were remarkable 14 days postinjury when the spleen increased significantly in size. In white pulp, the periarteriolar lymphoid sheaths were associated with follicles having central light zones, morphologically similar to germinal centers. With the progress of healing, pigment-containing cells were seen to accumulate in both white and red pulp regions. Moreover, compared to controls, the cells immunoreactive to anti-cytokines (TNF-α, TGF-β1) and -iNOS increased from the first days after wounding. The 14th day, the positive cells formed a dense network of reticular cells in central regions of lymphoid follicles and more frequent reactive leukocytes were detected within the red pulp. A higher number of lymphoid cells immunostained with anti-CD3ε were also observed in the perifollicular zone. The results suggest that the spleen of adult frogs is involved in skin wound healing with the expansion of lymphoid compartments. J. Morphol. 277:888-895, 2016. © 2016 Wiley Periodicals, Inc. PMID:27059432

  17. Tumor initiating and promoting activities of various benzo(a)pyrene metabolites in mouse skin

    Energy Technology Data Exchange (ETDEWEB)

    Slaga, T J; Bracken, W M; Viaje, A; Berry, D L; Fischer, S M; Miller, D R; Levin, W; Conney, A H; Yagi, H; Jerina, D M

    1977-01-01

    The skin tumor-initiating activities of the twelve isomeric phenols of BP revealed that 2-OHBP was as potent as BP while 11-OHBP was moderately active and the others were weak or inactive. However, 2-OHBP has not been shown to be formed from BP in the skin or any other tissue. The (-)-trans-7,8-diol of BP skin was found to be more active as a skin tumor initiator than BP suggesting that it is a proximal carcinogen. The data on carcinogenicity, mutagenicity and metabolism suggest that BP-7..beta.., 8..cap alpha..-diol-9..cap alpha.., 10..cap alpha..-epoxide is the ultimate carcinogenic form of BP. The skin tumor-initiating activities of the various BP metabolites correlate very well with their complete carcinogenic in mouse skin except for BP-7..beta.., 8..cap alpha..-diol-9..cap alpha.., 10..cap alpha..-epoxide. It was found to have skin tumor initiating activity but not complete carcinogenic activity. However, BP-7..beta.., 8..cap alpha..-diol-9..cap alpha.., 10..cap alpha..-epoxide was found to be a very potent complete carcinogen in newborn mice. It is possible that BP-7..beta.., 8..cap alpha..-diol-9..cap alpha.., 10..cap alpha..-epoxide is only a tumor initiator in which a promoting stimulus must be supplied for carcinogenic activity. A natural tumor promoting stimulus may be present in the newborn mouse. There is also a good correlation between the skin tumor initiating activities of the various BP metabolites and their mutagenic activity in the V79 mammalian cell mediated mutagenesis system.

  18. Flavanone silibinin treatment attenuates nitrogen mustard-induced toxic effects in mouse skin

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Anil K.; Tewari-Singh, Neera; Inturi, Swetha; Kumar, Dileep [Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045 (United States); Orlicky, David J. [Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045 (United States); Agarwal, Chapla [Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045 (United States); White, Carl W. [Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045USA (United States); Agarwal, Rajesh, E-mail: Rajesh.Agarwal@UCDenver.edu [Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045 (United States)

    2015-05-15

    Currently, there is no effective antidote to prevent skin injuries by sulfur mustard (SM) and nitrogen mustard (NM), which are vesicating agents with potential relevance to chemical warfare, terrorist attacks, or industrial/laboratory accidents. Our earlier report has demonstrated the therapeutic efficacy of silibinin, a natural flavanone, in reversing monofunctional alkylating SM analog 2-chloroethyl ethyl sulfide-induced toxic effects in mouse skin. To translate this effect to a bifunctional alkylating vesicant, herein, efficacy studies were carried out with NM. Topical application of silibinin (1 or 2 mg) 30 min after NM exposure on the dorsal skin of male SKH-1 hairless mice significantly decreased NM-induced toxic lesions at 24, 72 or 120 h post-exposure. Specifically, silibinin treatment resulted in dose-dependent reduction of NM-induced increase in epidermal thickness, dead and denuded epidermis, parakeratosis and microvesication. Higher silibinin dose also caused a 79% and 51%reversal in NM-induced increases in myeloperoxidase activity and COX-2 levels, respectively. Furthermore, silibinin completely prevented NM-induced H2A.X phosphorylation, indicating reversal of DNA damage which could be an oxidative DNA damage as evidenced by high levels of 8-oxodG in NM-exposed mouse skin that was significantly reversed by silibinin. Together, these findings suggest that attenuation of NM-induced skin injury by silibinin is due to its effects on the pathways associated with DNA damage, inflammation, vesication and oxidative stress. In conclusion, results presented here support the optimization of silibinin as an effective treatment of skin injury by vesicants. - Highlights: • Silibinin treatment attenuated nitrogen mustard (NM)-induced skin injury. • Silibinin affects pathways associated with DNA damage, inflammation and vesication. • The efficacy of silibinin could also be associated with oxidative stress. • These results support testing and optimization of

  19. High-power femtosecond-terahertz pulse induces a wound response in mouse skin

    Science.gov (United States)

    Kim, Kyu-Tae; Park, Jaehun; Jo, Sung Jin; Jung, Seonghoon; Kwon, Oh Sang; Gallerano, Gian Piero; Park, Woong-Yang; Park, Gun-Sik

    2013-08-01

    Terahertz (THz) technology has emerged for biomedical applications such as scanning, molecular spectroscopy, and medical imaging. Although a thorough assessment to predict potential concerns has to precede before practical utilization of THz source, the biological effect of THz radiation is not yet fully understood with scant related investigations. Here, we applied a femtosecond-terahertz (fs-THz) pulse to mouse skin to evaluate non-thermal effects of THz radiation. Analysis of the genome-wide expression profile in fs-THz-irradiated skin indicated that wound responses were predominantly mediated by transforming growth factor-beta (TGF-β) signaling pathways. We validated NFκB1- and Smad3/4-mediated transcriptional activation in fs-THz-irradiated skin by chromatin immunoprecipitation assay. Repeated fs-THz radiation delayed the closure of mouse skin punch wounds due to up-regulation of TGF-β. These findings suggest that fs-THz radiation initiate a wound-like signal in skin with increased expression of TGF-β and activation of its downstream target genes, which perturbs the wound healing process in vivo.

  20. Dissection of complex adult traits in a mouse synthetic population.

    Science.gov (United States)

    Burke, David T; Kozloff, Kenneth M; Chen, Shu; West, Joshua L; Wilkowski, Jodi M; Goldstein, Steven A; Miller, Richard A; Galecki, Andrzej T

    2012-08-01

    Finding the causative genetic variations that underlie complex adult traits is a significant experimental challenge. The unbiased search strategy of genome-wide association (GWAS) has been used extensively in recent human population studies. These efforts, however, typically find only a minor fraction of the genetic loci that are predicted to affect variation. As an experimental model for the analysis of adult polygenic traits, we measured a mouse population for multiple phenotypes and conducted a genome-wide search for effector loci. Complex adult phenotypes, related to body size and bone structure, were measured as component phenotypes, and each subphenotype was associated with a genomic spectrum of candidate effector loci. The strategy successfully detected several loci for the phenotypes, at genome-wide significance, using a single, modest-sized population (N = 505). The effector loci each explain 2%-10% of the measured trait variation and, taken together, the loci can account for over 25% of a trait's total population variation. A replicate population (N = 378) was used to confirm initially observed loci for one trait (femur length), and, when the two groups were merged, the combined population demonstrated increased power to detect loci. In contrast to human population studies, our mouse genome-wide searches find loci that individually explain a larger fraction of the observed variation. Also, the additive effects of our detected mouse loci more closely match the predicted genetic component of variation. The genetic loci discovered are logical candidates for components of the genetic networks having evolutionary conservation with human biology. PMID:22588897

  1. Quantitative measurements of oxidative stress in mouse skin induced by X-ray irradiation

    International Nuclear Information System (INIS)

    To find efficient methods to evaluate oxidative stress in mouse skin caused by X-ray irradiation, several markers and methodologies were examined. Hairless mice were irradiated with 50 Gy X-rays and skin homogenates or skin strips were prepared. Lipid peroxidation was measured using the skin homogenate as the level of thiobarbituric acid reactive substances. The level of lipid peroxidation increased with time after irradiation and was twice that of the control at 78 h. Electron spin resonance (ESR) spectra of skin strips showed a clear signal for the ascorbyl radical, which increased with time after irradiation in a manner similar to that of lipid peroxidation. To measure levels of glutathione (GSH) and its oxidized forms (GSSG) simultaneously, two high performance liquid chromatography (HPLC) methods, sample derivatization with 1-fluoro-2,4-dinitrobenzene and detection with a UV detector (method A) and no derivatization and detection with an electrochemical detector (method B), were compared and the latter was found to be better. No significant change was observed within 24 h after irradiation in the levels of GSH and GSSG measured by method B. The GSH/GSSG ratio may be a less sensitive parameter for the evaluation of acute oxidative stress caused by X-ray irradiation in the skin. Monitoring the ascorbyl radical seems to be a good way to evaluate oxidative stress in skin in vivo. (author)

  2. Arsenic-induced enhancement of ultraviolet radiation carcinogenesis in mouse skin: a dose-response study.

    OpenAIRE

    Burns, Fredric J.; Uddin, Ahmed N.; Wu, Feng; Nádas, Arthur; Rossman, Toby G.

    2004-01-01

    The present study was designed to establish the form of the dose-response relationship for dietary sodium arsenite as a co-carcinogen with ultraviolet radiation (UVR) in a mouse skin model. Hairless mice (strain Skh1) were fed sodium arsenite continuously in drinking water starting at 21 days of age at concentrations of 0.0, 1.25, 2.5, 5.0, and 10 mg/L. At 42 days of age, solar spectrum UVR exposures were applied three times weekly to the dorsal skin at 1.0 kJ/m2 per exposure until the experi...

  3. Skin barrier disruption by acetone: observations in a hairless mouse skin model

    NARCIS (Netherlands)

    Rissmann, R.; Oudshoorn, M.H.M.; Hennink, W.E.; Ponec, M.; Bouwstra, J.A.

    2009-01-01

    To disrupt the barrier function of the skin, different in vivo methods have been established, e.g., by acetone wiping or tape-stripping. In this study, the acetone-induced barrier disruption of hairless mice was investigated in order to establish a reliable model to study beneficial, long-term effec

  4. In Vivo SILAC-Based Proteomics Reveals Phosphoproteome Changes during Mouse Skin Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Sara Zanivan

    2013-02-01

    Full Text Available Cancer progresses through distinct stages, and mouse models recapitulating traits of this progression are frequently used to explore genetic, morphological, and pharmacological aspects of tumor development. To complement genomic investigations of this process, we here quantify phosphoproteomic changes in skin cancer development using the SILAC mouse technology coupled to high-resolution mass spectrometry. We distill protein expression signatures from our data that distinguish between skin cancer stages. A distinct phosphoproteome of the two stages of cancer progression is identified that correlates with perturbed cell growth and implicates cell adhesion as a major driver of malignancy. Importantly, integrated analysis of phosphoproteomic data and prediction of kinase activity revealed PAK4-PKC/SRC network to be highly deregulated in SCC but not in papilloma. This detailed molecular picture, both at the proteome and phosphoproteome level, will prove useful for the study of mechanisms of tumor progression.

  5. Curcumin Stimulates the Antioxidant Mechanisms in Mouse Skin Exposed to Fractionated γ-Irradiation

    Directory of Open Access Journals (Sweden)

    Ganesh Chandra Jagetia

    2015-01-01

    Full Text Available Fractionated irradiation is one of the important radiotherapy regimens to treat different types of neoplasia. Despite of the immense therapeutic gains accrued by delivering fractionated irradiation to tumors, the radiation burden on skin increases significantly. Low doses of irradiation to skin adversely affect its molecular and metabolic status. The use of antioxidant/s may help to alleviate the radiation-induced changes in the skin and allow delivering a higher dose of radiation to attain better therapeutic gains. Curcumin is an antioxidant and a free radical scavenging dietary supplement, commonly used as a flavoring agent in curries. Therefore, the effect of 100 mg/kg body weight curcumin was studied on the antioxidant status of mice skin exposed to a total dose of 10, 20 and 40 Gy γ-radiation below the rib cage delivered as a single fraction of 2 Gy per day for 5, 10 or 20 days. Skin biopsies from both the curcumin treated or untreated irradiated groups were collected for the biochemical estimations at various post-irradiation times. The irradiation of animals caused a dose dependent decline in the glutathione concentration, glutathione peroxidase, and superoxide dismutase activities and increased the lipid peroxidation in the irradiated skin. Curcumin treatment before irradiation resulted in a significant rise in the glutathione concentration and activities of both the glutathione peroxidase and superoxide dismutase enzymes in mouse skin, whereas lipid peroxidation declined significantly. The present study indicates that curcumin treatment increased the antioxidant status of mouse exposed to different doses of fractionated γ-radiation.

  6. Curcumin Stimulates the Antioxidant Mechanisms in Mouse Skin Exposed to Fractionated γ-Irradiation.

    Science.gov (United States)

    Jagetia, Ganesh Chandra; Rajanikant, Golgod Krishnamurthy

    2015-01-01

    Fractionated irradiation is one of the important radiotherapy regimens to treat different types of neoplasia. Despite of the immense therapeutic gains accrued by delivering fractionated irradiation to tumors, the radiation burden on skin increases significantly. Low doses of irradiation to skin adversely affect its molecular and metabolic status. The use of antioxidant/s may help to alleviate the radiation-induced changes in the skin and allow delivering a higher dose of radiation to attain better therapeutic gains. Curcumin is an antioxidant and a free radical scavenging dietary supplement, commonly used as a flavoring agent in curries. Therefore, the effect of 100 mg/kg body weight curcumin was studied on the antioxidant status of mice skin exposed to a total dose of 10, 20 and 40 Gy γ-radiation below the rib cage delivered as a single fraction of 2 Gy per day for 5, 10 or 20 days. Skin biopsies from both the curcumin treated or untreated irradiated groups were collected for the biochemical estimations at various post-irradiation times. The irradiation of animals caused a dose dependent decline in the glutathione concentration, glutathione peroxidase, and superoxide dismutase activities and increased the lipid peroxidation in the irradiated skin. Curcumin treatment before irradiation resulted in a significant rise in the glutathione concentration and activities of both the glutathione peroxidase and superoxide dismutase enzymes in mouse skin, whereas lipid peroxidation declined significantly. The present study indicates that curcumin treatment increased the antioxidant status of mouse exposed to different doses of fractionated γ-radiation. PMID:26785336

  7. Topical application of ochratoxin A causes DNA damage and tumor initiation in mouse skin.

    Directory of Open Access Journals (Sweden)

    Rahul Kumar

    Full Text Available Skin cancer is one of the most common forms of cancer and 2-3 million new cases are being diagnosed globally each year. Along with UV rays, environmental pollutants/chemicals including mycotoxins, contaminants of various foods and feed stuffs, could be one of the aetiological factors of skin cancer. In the present study, we evaluated the DNA damaging potential and dermal carcinogenicity of a mycotoxin, ochratoxin A (OTA, with the rationale that dermal exposure to OTA in workers may occur during their involvement in pre and post harvest stages of agriculture. A single topical application of OTA (20-80 µg/mouse resulted in significant DNA damage along with elevated γ-H2AX level in skin. Alteration in oxidative stress markers such as lipid peroxidation, protein carbonyl, glutathione content and antioxidant enzymes was observed in a dose (20-80 µg/mouse and time-dependent (12-72 h manner. The oxidative stress was further emphasized by the suppression of Nrf2 translocation to nucleus following a single topical application of OTA (80 µg/mouse after 24 h. OTA (80 µg/mouse application for 12-72 h caused significant enhancement in- (a reactive oxygen species generation, (b activation of ERK1/2, p38 and JNK MAPKs, (c cell cycle arrest at G0/G1 phase (37-67%, (d induction of apoptosis (2.0-11.0 fold, (e expression of p53, p21/waf1, (f Bax/Bcl-2 ratio, (g cytochrome c level, (h activities of caspase 9 (1.2-1.8 fold and 3 (1.7-2.2 fold as well as poly ADP ribose polymerase cleavage. In a two-stage mouse skin tumorigenesis protocol, it was observed that a single topical application of OTA (80 µg/mouse followed by twice weekly application of 12-O-tetradecanoylphorbol-13-acetate for 24 week leads to tumor formation. These results suggest that OTA has skin tumor initiating property which may be related to oxidative stress, MAPKs signaling and DNA damage.

  8. Mouse allergen-specific immunoglobulin G4 and risk of mouse skin test sensitivity

    NARCIS (Netherlands)

    E.C. Matsui; G.B. Diette; E.J.M. Krop; R.C. Aalberse; A.L. Smith; P.A. Eggleston

    2006-01-01

    Background High serum levels of cat-specific IgG and IgG4 are associated with protection against allergic sensitization to cat, but whether this association applies to other animal allergens remains unclear. Objective To determine if high levels of mouse-specific IgG and IgG4 are associated with a d

  9. The acute effects of different energy beta-emitters on pig and mouse skin

    International Nuclear Information System (INIS)

    Acute changes were studied in the skin of mice and pigs following irradiation with Sr90 (Esub(max) 2.27 MeV), Tm170 (Esub(max) 0.97 MeV) and Pm147 (Esub(max) 0.225 MeV). Sr90 irradiation in the pig and Sr90 and Tm170 exposure in the mouse resulted in a distinct field-size effect for sources of 5-22.5 mm diameter; ED50 values for moist desquamation were 22.0-27.5 Gy from the 22.5 mm source and 75-90 Gy for the 5 mm source. Tm170 irradiation in the pig produced no distinct area effect for sources of 5-19 mm diameter (ED50 approx.= 80 Gy). Acute tissue breakdown was only achieved in pig and mouse skin by very high doses (ED50 >= 140 Gy) from sources of 147 produced acute epithelial breakdown, only after high skin-surface doses (ED50 550-725 Gy). Area-and energy-related changes can, in part be explained by an hypothesis based on repopulation of the epithelium in the irradiated area by the migration of either cells from the edge of that area and/or cells surviving at the base of hair follicles. Differences in the results in pig and mouse can be explained on the basis of the distribution of target cells in the epidermis at varying depths. (author)

  10. Differential Apoptosis Radiosensitivity of Neural Progenitors in Adult Mouse Hippocampus

    Directory of Open Access Journals (Sweden)

    Yu-Qing Li

    2016-06-01

    Full Text Available Mammalian tissue-specific stem cells and progenitors demonstrate differential DNA damage response. Neural progenitors in dentate gyrus of the hippocampus are known to undergo apoptosis after irradiation. Using a mouse model of hippocampal neuronal development, we characterized the apoptosis sensitivity of the different neural progenitor subpopulations in adult mouse dentate gyrus after irradiation. Two different bromodeoxyuridine incorporation paradigms were used for cell fate mapping. We identified two apoptosis sensitive neural progenitor subpopulations after irradiation. The first represented non-proliferative and non-newborn neuroblasts and immature neurons that expressed doublecortin, calretinin or both. The second consisted of proliferative intermediate neural progenitors. The putative radial glia-like neural stem cells or type-1 cells, regardless of proliferation status, were apoptosis resistant after irradiation. There was no evidence of radiation-induced apoptosis in the absence of the Trp53 (p53 gene but absence of Cdkn1a (p21 did not alter the apoptotic response. Upregulation of nuclear p53 was observed in neuroblasts after irradiation. We conclude that adult hippocampal neural progenitors may demonstrate differential p53-dependent apoptosis sensitivity after irradiation.

  11. Induction of megakaryocytic colony-stimulating activity in mouse skin by inflammatory agents and tumor promoters

    Energy Technology Data Exchange (ETDEWEB)

    Clark, D.A.; Dessypris, E.N.; Koury, M.J.

    1987-03-01

    The production of megakaryocytic colony-stimulating activity (MEG-CSA) was assayed in acetic acid extracts of skin from mice topically treated with inflammatory and tumor-promoting agents. A rapid induction of MEG-CSA was found in skin treated both with phorbol 12-myristate 13-acetate (PMA), a strong tumor promoter, and with mezerein, a weak tumor promoter, but no induction was found in untreated skin. The time course of induction of MEG-CSA following treatment of skin with PMA or mezerein was very similar to that previously demonstrated for the induction of granulocyte-macrophage colony-stimulating activity in mouse skin by these agents. The induced MEG-CSA was found in both the epidermis and the dermis. Pretreatment of the skin with US -methasone abrogated the MEG-CSA induction. The cell number response curve suggests that the MEG-CSA acts directly on the progenitor cells of the megakaryocyte colonies. That topical administration of diterpene esters results in the rapid, local induction of MEG-CSA which can be blocked by US -methasone pretreatment suggests a mechanism for the thrombocytosis associated with some inflammatory states. The indirect action in which diterpene esters induce in certain cells the production or release of growth regulatory factors for other cell types may also aid in understanding their carcinogenic properties.

  12. LC-ESI-MS method for the determination of dexamethasone acetate in skin of nude mouse.

    Science.gov (United States)

    Li, Lingjun; Ma, Pengcheng; Wei, Jun; Qian, Kun; Tao, Lei

    2013-08-15

    A high-performance liquid chromatography-positive electrospray ionization single quadrupole mass spectrometric (LC-ESI-MS) method for the determination of dexamethasone acetate in skin of nude mouse using triamcinolone acetonide acetate as the internal standard (I.S.) was developed and fully validated. Both compounds were precipitated from skin homogenate with methanol and were separated by HPLC on a Shimadzu Shim-pack VP-ODS C18 column (150mm×2.0mm, 5μm) with a mobile phase of methanol-water (80:20, v/v) at a flow rate of 0.2mL/min. Calibration curves were linear over the range of 0.05-5μg/mL. The intra-run relative standard deviations were less than 9.59%. The inter-run relative standard deviations were less than 7.82%. The mean recovery was in the ranges of 89.95-95.97%, respectively. The method was successfully applied to determinate the concentration of dexamethasone acetate in skin and study the percutaneous absorption process in skin of nude mouse. PMID:23867829

  13. Ultraviolet light induction of skin carcinoma in the mouse; influence of cAMP modifying agents.

    Science.gov (United States)

    Zajdela, F; Latarjet, R

    1978-01-01

    A short review of pathogenic factors in U.V. light skin carcinogenesis in the mouse is presented. Caffeine and theophylline applied locally during U.V. irradiation caused a 50 percent reduction of skin tumour induction in Swiss mice. These two chemicals are inhibitors of DNA postreplication repair, but they also raise the intracellular level of cyclic AMP by inhibiting cAMP phosphodiesterase with, as a consequence, a possible slowing down of cellular growth. Control experiments using three different chemicals capable of raising the cAMP level in epidermal cells gave negative results. These experimental data are compatible with our original hypothesis according to which production of skin cancers by U.V. radiation is in same way related to DNA repair which helps the cell to survive but allows or favours the occurrence of errors in cellular DNA.

  14. Gene Expression Architecture of Mouse Dorsal and Tail Skin Reveals Functional Differences in Inflammation and Cancer

    Directory of Open Access Journals (Sweden)

    David A. Quigley

    2016-07-01

    Full Text Available Inherited germline polymorphisms can cause gene expression levels in normal tissues to differ substantially between individuals. We present an analysis of the genetic architecture of normal adult skin from 470 genetically unique mice, demonstrating the effect of germline variants, skin tissue location, and perturbation by exogenous inflammation or tumorigenesis on gene signaling pathways. Gene networks related to specific cell types and signaling pathways, including sonic hedgehog (Shh, Wnt, Lgr family stem cell markers, and keratins, differed at these tissue sites, suggesting mechanisms for the differential susceptibility of dorsal and tail skin to development of skin diseases and tumorigenesis. The Pten tumor suppressor gene network is rewired in premalignant tumors compared to normal tissue, but this response to perturbation is lost during malignant progression. We present a software package for expression quantitative trait loci (eQTL network analysis and demonstrate how network analysis of whole tissues provides insights into interactions between cell compartments and signaling molecules.

  15. Gene Expression Architecture of Mouse Dorsal and Tail Skin Reveals Functional Differences in Inflammation and Cancer.

    Science.gov (United States)

    Quigley, David A; Kandyba, Eve; Huang, Phillips; Halliwill, Kyle D; Sjölund, Jonas; Pelorosso, Facundo; Wong, Christine E; Hirst, Gillian L; Wu, Di; Delrosario, Reyno; Kumar, Atul; Balmain, Allan

    2016-07-26

    Inherited germline polymorphisms can cause gene expression levels in normal tissues to differ substantially between individuals. We present an analysis of the genetic architecture of normal adult skin from 470 genetically unique mice, demonstrating the effect of germline variants, skin tissue location, and perturbation by exogenous inflammation or tumorigenesis on gene signaling pathways. Gene networks related to specific cell types and signaling pathways, including sonic hedgehog (Shh), Wnt, Lgr family stem cell markers, and keratins, differed at these tissue sites, suggesting mechanisms for the differential susceptibility of dorsal and tail skin to development of skin diseases and tumorigenesis. The Pten tumor suppressor gene network is rewired in premalignant tumors compared to normal tissue, but this response to perturbation is lost during malignant progression. We present a software package for expression quantitative trait loci (eQTL) network analysis and demonstrate how network analysis of whole tissues provides insights into interactions between cell compartments and signaling molecules. PMID:27425619

  16. Reduction in squamous cell carcinomas in mouse skin by dietary zinc supplementation.

    Science.gov (United States)

    Sun, Jin; Shen, Rulong; Schrock, Morgan S; Liu, James; Pan, Xueliang; Quimby, Donald; Zanesi, Nicola; Druck, Teresa; Fong, Louise Y; Huebner, Kay

    2016-08-01

    Inadequate dietary Zn consumption increases susceptibility to esophageal and other cancers in humans and model organisms. Since Zn supplementation can prevent cancers in rodent squamous cell carcinoma (SCC) models, we were interested in determining if it could have a preventive effect in a rodent skin cancer model, as a preclinical basis for considering a role for Zn in prevention of human nonmelanoma skin cancers, the most frequent cancers in humans. We used the 7,12-dimethyl benzanthracene carcinogen/phorbol myristate acetate tumor promoter treatment method to induce skin tumors in Zn-sufficient wild-type and Fhit (human or mouse protein) knockout mice. Fhit protein expression is lost in >50% of human cancers, including skin SCCs, and Fhit-deficient mice show increased sensitivity to carcinogen induction of tumors. We hypothesized that: (1) the skin cancer burdens would be reduced by Zn supplementation; (2) Fhit(-/-) (Fhit, murine fragile histidine triad gene) mice would show increased susceptibility to skin tumor induction versus wild-type mice. 30 weeks after initiating treatment, the tumor burden was increased ~2-fold in Fhit(-/-) versus wild-type mice (16.2 versus 7.6 tumors, P < 0.001); Zn supplementation significantly reduced tumor burdens in Fhit(-/-) mice (males and females combined, 16.2 unsupplemented versus 10.3 supplemented, P = 0.001). Most importantly, the SCC burden was reduced after Zn supplementation in both strains and genders of mice, most significantly in the wild-type males (P = 0.035). Although the mechanism(s) of action of Zn supplementation in skin tumor prevention is not known in detail, the Zn-supplemented tumors showed evidence of reduced DNA damage and some cohorts showed reduced inflammation scores. The results suggest that mild Zn supplementation should be tested for prevention of skin cancer in high-risk human cohorts. PMID:27185213

  17. Skin-derived mesenchymal stem cells help restore function to ovaries in a premature ovarian failure mouse model.

    Directory of Open Access Journals (Sweden)

    Dongmei Lai

    Full Text Available Skin-derived mesenchymal stem cells (SMSCs can differentiate into the three embryonic germ layers. For this reason, they are considered a powerful tool for therapeutic cloning and offer new possibilities for tissue therapy. Recent studies showed that skin-derived stem cells can differentiate into cells expressing germ-cell specific markers in vitro and form oocytes in vivo. The idea that SMSCs may be suitable for the treatment of intractable diseases or traumatic tissue damage has attracted attention. To determine the ability of SMSCs to reactivate injured ovaries, a mouse model with ovaries damaged by busulfan and cyclophosphamide was developed and is described here. Female skin-derived mesenchymal stem cells (F-SMSCs and male skin-derived mesenchymal stem cells (M-SMSCs from red fluorescence protein (RFP transgenic adult mice were used to investigate the restorative effects of SMSCs on ovarian function. Significant increases in total body weight and the weight of reproductive organs were observed in the treated animals. Both F-SMSCs and M-SMSCs were shown to be capable of partially restoring fertility in chemotherapy-treated females. Immunostaining with RFP and anti-Müllerian hormone (AMH antibodies demonstrated that the grafted SMSCs survived, migrated to the recipient ovaries. After SMSCs were administered to the treated mice, real-time PCR showed that the expression levels of pro-inflammatory cytokines TNF-α, TGF-β, IL-8, IL-6, IL-1β, and IFNγ were significantly lower in the ovaries than in the untreated controls. Consistent with this observation, expression of oogenesis marker genes Nobox, Nanos3, and Lhx8 increased in ovaries of SMSCs-treated mice. These findings suggest that SMSCs may play a role within the ovarian follicle microenvironment in restoring the function of damaged ovaries and could be useful in reproductive health.

  18. The management of skin and skin structure infections in children, adolescents and adults: a review of empiric antimicrobial therapy.

    Science.gov (United States)

    Wilson, S E

    1998-09-01

    This article reviews the diagnosis and management of mild-to-moderate skin and skin structure infections in children, adolescents and adults in a general practice setting. Therapies reviewed are those in current use: penicillins; beta-lactamase stable penicillins, including flucloxacillin, oxacillin, and amoxicillin-clavulanate; oral quinolones; macrolides; and oral cephalosporins. Consideration is given to duration of therapy, side-effect profile and compliance.

  19. A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures

    International Nuclear Information System (INIS)

    Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. - Highlights: • An ARID3a-deficient mouse kidney cell line expresses multiple progenitor markers. • This cell line spontaneously forms multiple nephron-like structures in vitro. • This cell line formed mouse kidney structures in immunocompromised medaka fish kidneys. • Our data identify a novel model system for studying kidney development

  20. A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures

    Energy Technology Data Exchange (ETDEWEB)

    Webb, Carol F., E-mail: carol-webb@omrf.org [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Immunobiology and Cancer Research, Oklahoma Medical Research Foundation, Oklahoma City, OK (United States); Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Ratliff, Michelle L., E-mail: michelle-ratliff@omrf.org [Immunobiology and Cancer Research, Oklahoma Medical Research Foundation, Oklahoma City, OK (United States); Powell, Rebecca, E-mail: rebeccapowell@gmail.com [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Wirsig-Wiechmann, Celeste R., E-mail: celeste-wirsig@ouhsc.edu [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Lakiza, Olga, E-mail: olga-lakiza@ouhsc.edu [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Obara, Tomoko, E-mail: tomoko-obara@ouhsc.edu [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States)

    2015-08-07

    Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. - Highlights: • An ARID3a-deficient mouse kidney cell line expresses multiple progenitor markers. • This cell line spontaneously forms multiple nephron-like structures in vitro. • This cell line formed mouse kidney structures in immunocompromised medaka fish kidneys. • Our data identify a novel model system for studying kidney development.

  1. Cutaneous Surgical Denervation: A Method for Testing the Requirement for Nerves in Mouse Models of Skin Disease.

    Science.gov (United States)

    Peterson, Shelby C; Brownell, Isaac; Wong, Sunny Y

    2016-01-01

    Cutaneous somatosensory nerves function to detect diverse stimuli that act upon the skin. In addition to their established sensory roles, recent studies have suggested that nerves may also modulate skin disorders including atopic dermatitis, psoriasis and cancer. Here, we describe protocols for testing the requirement for nerves in maintaining a cutaneous mechanosensory organ, the touch dome (TD). Specifically, we discuss methods for genetically labeling, harvesting and visualizing TDs by whole-mount staining, and for performing unilateral surgical denervation on mouse dorsal back skin. Together, these approaches can be used to directly compare TD morphology and gene expression in denervated as well as sham-operated skin from the same animal. These methods can also be readily adapted to examine the requirement for nerves in mouse models of skin pathology. Finally, the ability to repeatedly sample the skin provides an opportunity to monitor disease progression at different stages and times after initiation. PMID:27404892

  2. An anatomic gene expression atlas of the adult mouse brain.

    Science.gov (United States)

    Ng, Lydia; Bernard, Amy; Lau, Chris; Overly, Caroline C; Dong, Hong-Wei; Kuan, Chihchau; Pathak, Sayan; Sunkin, Susan M; Dang, Chinh; Bohland, Jason W; Bokil, Hemant; Mitra, Partha P; Puelles, Luis; Hohmann, John; Anderson, David J; Lein, Ed S; Jones, Allan R; Hawrylycz, Michael

    2009-03-01

    Studying gene expression provides a powerful means of understanding structure-function relationships in the nervous system. The availability of genome-scale in situ hybridization datasets enables new possibilities for understanding brain organization based on gene expression patterns. The Anatomic Gene Expression Atlas (AGEA) is a new relational atlas revealing the genetic architecture of the adult C57Bl/6J mouse brain based on spatial correlations across expression data for thousands of genes in the Allen Brain Atlas (ABA). The AGEA includes three discovery tools for examining neuroanatomical relationships and boundaries: (1) three-dimensional expression-based correlation maps, (2) a hierarchical transcriptome-based parcellation of the brain and (3) a facility to retrieve from the ABA specific genes showing enriched expression in local correlated domains. The utility of this atlas is illustrated by analysis of genetic organization in the thalamus, striatum and cerebral cortex. The AGEA is a publicly accessible online computational tool integrated with the ABA (http://mouse.brain-map.org/agea). PMID:19219037

  3. "Mirror, mirror...." a preliminary investigation of skin tone dissatisfaction and its impact among British adults.

    Science.gov (United States)

    Swami, Viren; Henry, Amy; Peacock, Nicola; Roberts-Dunn, Ahkin; Porter, Alan

    2013-10-01

    This study examined skin tone dissatisfaction, measured using a skin tone chart, among a multiethnic sample of British adults. A total of 648 British White individuals, 292 British South Asians, and 260 British African Caribbean participants completed a visual task in which they were asked to indicate their actual and ideal skin tones. They also completed measures of body appreciation, self-esteem, and ethnic identity attachment. Results showed that Asians had a lighter skin tone ideal than White and African Caribbean participants. Conversely, White participants had higher skin tone dissatisfaction (preferring a darker skin tone) than Asian and African Caribbean participants, who preferred a lighter skin tone. Results also showed that skin tone dissatisfaction predicted body appreciation once the effects of participant ethnicity, age, ethnic identity attachment, and self-esteem had been accounted for. Implications of our findings and suggestions for future research are discussed.

  4. Effects of Nicotinamide on Mouse Skin Tumor Development and lts Mode of Action

    Institute of Scientific and Technical Information of China (English)

    KRISHNA P. GUPTA

    1999-01-01

    Nicotinamide (NA), a naturally occuring vitamin and a protease inhibitor, has been shown to be effective in treating some skin ailments. It inhibits cell proliferation and induces cell differentiation. This report shows the effects of NA on mouse skin tumor development and on the critical events involved in this process. NA reduced tumor growth, inhibited the 12-O-tetradecanoylphorbol- 13-acetate (TPA) induced ornithine decarboxylase activity, but induced the transglutaminase activity which was inhibited by TPA under different experimental conditions.The effects of NA on ornithine decarboxylase (ODC) and transglutaminase (TG) indicated that nicotinamide (NA) probably programmmed the cells for their death in the natural course of time, I.e. Programed cell death. This observation indicates that NA might be a better agent for the detailed study and for the better use in prevention of cancer alone or in combination with other drugs.

  5. Expression and significance of EGFR protein in model of radiation injury in mouse skin

    International Nuclear Information System (INIS)

    Objective: The expression of EGFR protein was studied by SABC immunohistochemistry in 40 cases of model of radiation injury in mouse skin. Methods: Experiment animals were divided into four groups according to radiation dose. Results: The positive rates were 27.0%, 49.3%, 72.2%, 87.6% in 5 Gy group, 15 Gy group, 30 Gy group, 45 Gy group respectively, showing significant difference (P < 0.01). While the positive rate was 10.8% in normal control group, with significant difference (P < 0.01) compared with each radiation group. Conclusion: The enhancement of expression of EGFR in accordance with the increasing of radiation dose in certain dose range might be one important factor related to c-erbB-1 gene activated and enlarged by radiation, and the overexpression of EGFR protein might be related to poor healing in radiation skin injury

  6. Life science research using positron annihilation spectroscopy: UV-irradiated mouse skin

    Energy Technology Data Exchange (ETDEWEB)

    Jean, Y.C. [Department of Chemistry, University of Missouri-Kansas City, Kansas City, MO 64110-2499 (United States)]. E-mail: jeany@umkc.edu; Chen, Hongmin [Department of Chemistry, University of Missouri-Kansas City, Kansas City, MO 64110-2499 (United States); Liu Guang [Department of Chemistry, University of Missouri-Kansas City, Kansas City, MO 64110-2499 (United States); Gadzia, Joseph E. [Dermatology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS 66103 (United States); Kansas Medical Clinic, Topeka, KS 66614 (United States)

    2007-02-15

    Positron annihilation spectroscopy (PAS) is applied to study mouse skin under different UV irradiations as a function of positron incident energy (0-30 keV). Significant variations in the depth profile of S parameter are observed in a period of hours and of days for UVA and UVB exposures, respectively. The high sensitivity of positron annihilation signals responding to UV irradiation shows that PAS may be developed as a new noninvasive technique for the detection of molecular damage in life science research.

  7. Mouse skin reactions to 40 MeV helium ion irradiation

    International Nuclear Information System (INIS)

    The change of mouse skin was recorded periodically. Mice are periodically sacrificed to obtain irradiated skin specimens. The specimens are made into microscopic study preparations. 4He ion radiation dose applied to the skin ranges from 2,000 rads to 12,000 rads. 40MeV 4He ion beam is fairly stable. The study was repeated four times in total. When the beam position is in the center of scattering foil, Cobalt-60 gamma ray calibrateb one rad corresponded to 20-23 scattering 4He ion count detected by a solid state detector placed in the direction of 40 degree to the axis of down stream beam. One rad also corresponded to 0.52-0.55 nano-Ampere Farady cnp current placed in the center axis 80 centi-meter apart from the target foil. Monitoring with Farady cup current is more consistent, in which beam deviation from the center can not be detected. Hence the dose was monitored with the current with scattering helium count recorded. Depth dose was measured with TLD and 50% depth dose of plateau is approximately 0.08 g/cm. The skin was irradiated from 2,000 rads to 12,000 rads. In one week epilation starts. In two week complete epilation in all groups and in high dose groups (above 4,000 rads) at the same time erosions occur. In four weeks erosions heal. Higher dose group takes a little longer. In five weeks all erosins heal any way. Even the skin irradiated with 12,000 rads heals. Skin hypertrophy follows. The higher dose induces the more hypertrophy. Cell number in a hair follicle decreases with increased dose. Hair follicle itself decreases its number. (J.P.N.)

  8. Anti-tumour promoting activity of diphenylmethyl selenocyanate against two-stage mouse skin carcinogenesis.

    Science.gov (United States)

    Das, Rajat Kumar; Bhattacharya, Sudin

    2005-01-01

    Epidemiological, clinical and experimental evidence collectively suggests that Se in different inorganic and organic forms provides a potential cancer chemopreventive agent, active against several types of cancer. It can exert preventive activity in all the three stages of cancer: initiation, promotion and progression. Literature reports revealed that organoselenocyanates have more potential as chemopreventive agents than inorganic forms due to their lower toxicity. In our previous report we showed chemopreventive efficacy of diphenylmethyl selenocyanate during the initiation and pre- plus post-initiation phases of skin and colon carcinogenesis process. The present study was undertaken to explore the anti-tumour promoting activity of diphenylmethyl selenocyanate in a 7,12-dimethylbenz (a) anthracene (DMBA)-croton oil two-stage skin carcinogenesis model. The results obtained showed significant (pliver and skin. Thus, the present data strongly suggest that diphenylmethyl selenocyanate also has the potential to act as anti-tumour promoter agent in a two-stage skin carcinogenesis mouse model, pointing to possible general efficacy. PMID:16101330

  9. Beliefs and Intentions for Skin Protection and UV Exposure in Young Adults

    Science.gov (United States)

    Heckman, Carolyn J.; Manne, Sharon L.; Kloss, Jacqueline D.; Bass, Sarah Bauerle; Collins, Bradley; Lessin, Stuart R.

    2011-01-01

    Objective: To evaluate Fishbein's integrative model in predicting young adults' skin protection, sun exposure, and indoor tanning intentions. Methods: Two hundred twelve participants completed an online survey. Results: Damage distress, self-efficacy, and perceived control accounted for 34% of the variance in skin protection intentions. Outcome…

  10. Deoxynivalenol induced mouse skin cell proliferation and inflammation via MAPK pathway

    International Nuclear Information System (INIS)

    Several toxicological manifestations of deoxynivalenol (DON), a mycotoxin, are well documented; however, dermal toxicity is not yet explored. The effect of topical application of DON to mice was studied using markers of skin proliferation, inflammation and tumor promotion. Single topical application of DON (84–672 nmol/mouse) significantly enhanced dermal hyperplasia and skin edema. DON (336 and 672 nmol) caused significant enhancement in [3H]-thymidine uptake in DNA along with increased myeloperoxidase and ornithine decarboxylase activities, suggesting tissue inflammation and cell proliferation. Furthermore, DON (168 nmol) caused enhanced expression of RAS, and phosphorylation of PI3K/Akt, ERK, JNK and p38 MAPKs. DON exposure also showed activation of transcription factors, c-fos, c-jun and NF-κB along with phosphorylation of IkBα. Enhanced phosphorylation of NF-κB by DON caused over expression of target proteins, COX-2, cyclin D1 and iNOS in skin. Though a single topical application of DMBA followed by twice weekly application of DON (84 and 168 nmol) showed no tumorigenesis after 24 weeks, however, histopathological studies suggested hyperplasia of the epidermis and hypertrophy of hair follicles. Interestingly, intestine was also found to be affected as enlarged Peyer's patches were observed, suggesting inflammatory effects which were supported by elevation of inflammatory cytokines after 24 weeks of topical application of DON. These results suggest that DON induced cell proliferation in mouse skin is through the activation of MAPK signaling pathway involving transcription factors NFκB and AP-1, further leading to transcriptional activation of downstream target proteins c-fos, c-jun, cyclin D1, iNOS and COX-2 which might be responsible for its inflammatory potential. - Highlights: • Topical application of DON enhanced epidermal inflammation and cell proliferation. • DON follows PI3K/Akt/MAPK signaling cascade, with activation of AP-1 and NF-κB.

  11. Deoxynivalenol induced mouse skin cell proliferation and inflammation via MAPK pathway

    Energy Technology Data Exchange (ETDEWEB)

    Mishra, Sakshi [Food Drug and Chemical Toxicology, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), P.O. Box No. 80, Mahatma Gandhi Marg, Lucknow 226 001 (India); Department of Biochemistry, Banaras Hindu University (BHU), Varanasi (India); Tripathi, Anurag [Food Drug and Chemical Toxicology, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), P.O. Box No. 80, Mahatma Gandhi Marg, Lucknow 226 001 (India); Chaudhari, Bhushan P. [Pathology Laboratory, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Mahatma Gandhi Marg, PO Box 80, Lucknow 226001, Uttar Pradesh (India); Dwivedi, Premendra D. [Food Drug and Chemical Toxicology, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), P.O. Box No. 80, Mahatma Gandhi Marg, Lucknow 226 001 (India); Pandey, Haushila P. [Department of Biochemistry, Banaras Hindu University (BHU), Varanasi (India); Das, Mukul, E-mail: mditrc@rediffmail.com [Food Drug and Chemical Toxicology, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), P.O. Box No. 80, Mahatma Gandhi Marg, Lucknow 226 001 (India)

    2014-09-01

    Several toxicological manifestations of deoxynivalenol (DON), a mycotoxin, are well documented; however, dermal toxicity is not yet explored. The effect of topical application of DON to mice was studied using markers of skin proliferation, inflammation and tumor promotion. Single topical application of DON (84–672 nmol/mouse) significantly enhanced dermal hyperplasia and skin edema. DON (336 and 672 nmol) caused significant enhancement in [{sup 3}H]-thymidine uptake in DNA along with increased myeloperoxidase and ornithine decarboxylase activities, suggesting tissue inflammation and cell proliferation. Furthermore, DON (168 nmol) caused enhanced expression of RAS, and phosphorylation of PI3K/Akt, ERK, JNK and p38 MAPKs. DON exposure also showed activation of transcription factors, c-fos, c-jun and NF-κB along with phosphorylation of IkBα. Enhanced phosphorylation of NF-κB by DON caused over expression of target proteins, COX-2, cyclin D1 and iNOS in skin. Though a single topical application of DMBA followed by twice weekly application of DON (84 and 168 nmol) showed no tumorigenesis after 24 weeks, however, histopathological studies suggested hyperplasia of the epidermis and hypertrophy of hair follicles. Interestingly, intestine was also found to be affected as enlarged Peyer's patches were observed, suggesting inflammatory effects which were supported by elevation of inflammatory cytokines after 24 weeks of topical application of DON. These results suggest that DON induced cell proliferation in mouse skin is through the activation of MAPK signaling pathway involving transcription factors NFκB and AP-1, further leading to transcriptional activation of downstream target proteins c-fos, c-jun, cyclin D1, iNOS and COX-2 which might be responsible for its inflammatory potential. - Highlights: • Topical application of DON enhanced epidermal inflammation and cell proliferation. • DON follows PI3K/Akt/MAPK signaling cascade, with activation of AP-1 and NF

  12. Epithelial cell kinetics in mouse and rat skin irradiated with electrons

    International Nuclear Information System (INIS)

    Experiments were performed to examine the kinetic responses of mouse and rat epidermal cells in vivo after single doses of ionizing radiation including responses of hair follicles at times after irradiation. The labeling indices in both species were reduced to 30 to 50% of control values immediately following irradiation at all the doses. In the rat, the labeling indices recovered and overshot control values within the first three days after 300 to 1200 rads. The mouse labeling indices continued to be suppressed for up to 10 days after 300 to 2400 rads. This indicated that rat G1 phase epidermal cells recovered three times faster than those of the mouse with respect to the ability to maintain or increase control level cell proliferation after irradiation. After 1800 and 2400 rads, doses which produce skin ulceration, both species showed a reduction in their labeling indices for up to 7 days, indicating that a dose-dependent mechanism of recovery may be operable in the rat. 99 refs., 15 figs., 6 tabs

  13. Chandelier and interfascicular neurons in the adult mouse piriform cortex

    Directory of Open Access Journals (Sweden)

    Jorge A Larriva-Sahd

    2010-12-01

    Full Text Available The structure of two neuron types native to the adult mouse piriform cortex (PC is described. The first cell, termed an interfascicular neuron (IFN, lies between the axon fascicles of layer I. The IFN axon divides dichotomously and daughter fibrils run horizontally in the domain of layer Ia. The frequent apposition of the IFN axon to distal denrites of the underlying pyramidal cells suggests an en passage synaptic interaction with them. A second neuron observed in layer II, or less frequently in layer III, matched in most respects the structure of the chandelier cell described elsewhere in the neo- and archi-cortex. In the PC, chandelier cells (PC-CC display the following peculiarities. First, the PC-CC axonal field distributes in the neuropil of layers II and III and candlesticks are in close apposition to the initial axonal segment of the pyramidal cell, although somatic interactions cannot be rule out. Second, the PC-CC ascending dendrites pierce layer I, receiving short collaterals and boutons en passage from the olfactory axons therein. The possible role of IFN´s and PC-CC and their interactions with the adjacent cells is discussed in the broad context of the cellular organization of the PC.

  14. Study of the mechanisms of flux enhancement through hairless mouse skin by pulsed DC iontophoresis

    Energy Technology Data Exchange (ETDEWEB)

    Pikal, M.J.; Shah, S. (Lilly Research Laboratories, Eli Lilly Co., Indianapolis, IN (USA))

    1991-03-01

    Enhanced iontophoretic transport using pulsed DC is usually explained by citing the observed decrease in skin resistance caused by an increase in AC pulse frequency at very small currents. Alternately, it has been suggested that the on-to-off nature of pulsed DC imparts an impact energy to the fluid, thereby increasing transport. This report provides a test of these mechanisms for enhanced delivery via pulsed iontophoresis. The DC resistance of hairless mouse skin during continuous and pulsed DC iontophoresis is measured as a function of time for selected pulse frequencies and duty cycles using current densities ranging from 0.1 to 1.0 mA/cm2. As a test of the impact energy mechanism, the iontophoretic transport of 14C-glucose measured with pulsed DC is compared with similar data obtained previously using continuous DC. It is suggested that pulsed current can yield lower resistance and enhanced drug delivery provided that (a) the steady-state current during the on phase of the pulse is very small and (b) the frequency is low enough to allow depolarization of the skin during the off phase of the pulse. The glucose transport results suggest that the impact energy concept does not apply to iontophoresis.

  15. The co-application effects of fullerene and ascorbic acid on UV-B irradiated mouse skin

    International Nuclear Information System (INIS)

    The role of fullerene as a pro-oxidant or anti-oxidant in Ultraviolet B ray (UV-B)-induced disorders in mouse skin was investigated. Fullerene gave no photo-toxic effect to UV-B-irradiated mouse skin. Since erythema was concentrated at the pore circumference in a UV-B irradiation experiment in mouse skin, the sebaceous gland pairs was strongly implicated as a site for the generation of reactive oxygen species (ROS). In a histological evaluation of the skin stained with CH3MDFDA (ROS index) and YO-Pro-1 (apoptosis index), the fluorescence intensity of a sebaceous gland significantly increased with UV-B irradiation. With the application of fullerene to UV-irradiated mouse skin, no toxicity was recognized in comparison with the control, and erythema, the ROS index, and the apoptosis index decrease with the application of fullerene. Ascorbyl radical (AA·) increased with the application of ascorbate (AA) to UV-B-irradiated mouse skin, and AA· decreased with the application of fullerene. The co-application of AA and fullerene, which suppressed AA· in vitro, significantly suppressed erythema, and also suppressed both the ROS index and apoptosis index in mouse skin after UV-B irradiation. In both mouse skin at 48 h after UV-B irradiation and in an attempt to reproduce this phenomenon artificially in vitro, a similar high AA· peak (AA·/H· > 4) was observed in electron spin resonance (ESR) charts. The binding of fullerene with AA impairs the Fenton reaction between AA and Fe-protein based on the observation of ascorbate-specific UV absorption and a linear equation for the calibration curve. Therefore, fullerene may impair the intercalation of AA to a heme pocket by binding with AA. These results suggest that the co-application of AA and fullerene is effective against oxidative skin damage caused by UV-B irradiation, and the development of an AA· inhibitor such as fullerene should be useful for reducing organ damage associated with Fe-protein oxidation.

  16. Evaluation of Skin Findings in Adult Obese Dermatology Outpatients

    Directory of Open Access Journals (Sweden)

    Hilal

    2011-12-01

    Full Text Available Background: The relationship between systemic diseases and obesity is well-known, but the dermatological effects of obesity are ignored. In the literature, a few articles have appeared concerning the skin findings related to obesity. Our objective was to evaluate the skin findings in obese patients who applied to dermatology outpatient clinic and to compare obese and non-obese outpatients. Material and Method: A total 640 patients (300-in study group, 340-in control group were included in the study. All subjects were asked questions about socio-demographic features and presence of coexisting systemic diseases. Body mass index was calculated, dermatologic examination was performed, and diagnosis was recorded. Data were evaluated statistically. Results: Three-hundred obese patients (study group; 229 females, 71 males, mean age: 45.89 years and 340 non-obese outpatients (control group; 160 females, 180 males, mean age: 38.99 years were included in our study. There were more females in the study group and the mean age was higher than the control group. Most common skin findings of obese patients were: Skin tag (53.3%, plantar hyperkeratosis (29.6%, fungal infections (25.3%, striae (20.3% and acanthosis nigricans (15.3%. Fungal infections, intertrigo, varicose veins and keratosis pilaris were more common in females than males in the study group. Within the study group, patients with skin tag, acanthosis nigricans and plantar hyperkeratosis had higher BMI.Conclusion: Skin tag, plantar hyperkeratosis, fungal infections, striae and acanthosis nigricans were found to be the most common skin diseases in obese patients in our study. Studies related with pathophysiologic features of the skin of obese patients will give more information about the development and treatment of these diseases. (Turk­derm 2011; 45: 184-7

  17. Xenobiotic-metabolizing enzymes in the skin of rat, mouse, pig, guinea pig, man, and in human skin models

    OpenAIRE

    Oesch, F; Fabian, E.; Guth, K.; Landsiedel, R.

    2014-01-01

    Abstract The exposure of the skin to medical drugs, skin care products, cosmetics, and other chemicals renders information on xenobiotic-metabolizing enzymes (XME) in the skin highly interesting. Since the use of freshly excised human skin for experimental investigations meets with ethical and practical limitations, information on XME in models comes in the focus including non-human mammalian species and in vitro skin models. This review attempts to summarize the information available in the ...

  18. Establishment of leptin-Responsive cell lines from adult mouse hypothalamus

    OpenAIRE

    Iwakura, Hiroshi; Dote, Katsuko; Bando, Mika; Koyama, Hiroyuki; Hosoda, Kiminori; Kangawa, Kenji; Nakao, Kazuwa

    2016-01-01

    Leptin resistance is considered to be the primary cause of obesity. However, the cause of leptin resistance remains incompletely understood, and there is currently no cure for the leptin-resistant state. In order to identify novel drug-target molecules that could overcome leptin resistance, it would be useful to develop in vitro assay systems for evaluating leptin resistance. In this study, we established immortalized adult mouse hypothalamus-derived cell lines, termed adult mouse hypothalamu...

  19. Establishment of Leptin-Responsive Cell Lines from Adult Mouse Hypothalamus

    OpenAIRE

    Hiroshi Iwakura; Katsuko Dote; Mika Bando; Hiroyuki Koyama; Kiminori Hosoda; Kenji Kangawa; Kazuwa Nakao

    2016-01-01

    Leptin resistance is considered to be the primary cause of obesity. However, the cause of leptin resistance remains incompletely understood, and there is currently no cure for the leptin-resistant state. In order to identify novel drug-target molecules that could overcome leptin resistance, it would be useful to develop in vitro assay systems for evaluating leptin resistance. In this study, we established immortalized adult mouse hypothalamus-derived cell lines, termed adult mouse hypothalamu...

  20. Regional genome transcriptional response of adult mouse brain to hypoxia

    Directory of Open Access Journals (Sweden)

    Lu Aigang

    2011-10-01

    Full Text Available Abstract Background Since normal brain function depends upon continuous oxygen delivery and short periods of hypoxia can precondition the brain against subsequent ischemia, this study examined the effects of brief hypoxia on the whole genome transcriptional response in adult mouse brain. Result Pronounced changes of gene expression occurred after 3 hours of hypoxia (8% O2 and after 1 hour of re-oxygenation in all brain regions. The hypoxia-responsive genes were predominantly up-regulated in hindbrain and predominantly down-regulated in forebrain - possibly to support hindbrain survival functions at the expense of forebrain cognitive functions. The up-regulated genes had a significant role in cell survival and involved both shared and unshared signaling pathways among different brain regions. Up-regulation of transcriptional signaling including hypoxia inducible factor, insulin growth factor (IGF, the vitamin D3 receptor/retinoid X nuclear receptor, and glucocorticoid signaling was common to many brain regions. However, many of the hypoxia-regulated target genes were specific for one or a few brain regions. Cerebellum, for example, had 1241 transcripts regulated by hypoxia only in cerebellum but not in hippocampus; and, 642 (54% had at least one hepatic nuclear receptor 4A (HNF4A binding site and 381 had at least two HNF4A binding sites in their promoters. The data point to HNF4A as a major hypoxia-responsive transcription factor in cerebellum in addition to its known role in regulating erythropoietin transcription. The genes unique to hindbrain may play critical roles in survival during hypoxia. Conclusion Differences of forebrain and hindbrain hypoxia-responsive genes may relate to suppression of forebrain cognitive functions and activation of hindbrain survival functions, which may coordinately mediate the neuroprotection afforded by hypoxia preconditioning.

  1. Self-Antigen Presentation by Keratinocytes in the Inflamed Adult Skin Modulates T-Cell Auto-Reactivity.

    Science.gov (United States)

    Meister, Michael; Tounsi, Amel; Gaffal, Evelyn; Bald, Tobias; Papatriantafyllou, Maria; Ludwig, Julia; Pougialis, Georg; Bestvater, Felix; Klotz, Luisa; Moldenhauer, Gerhard; Tüting, Thomas; Hämmerling, Günter J; Arnold, Bernd; Oelert, Thilo

    2015-08-01

    Keratinocytes have a pivotal role in the regulation of immune responses, but the impact of antigen presentation by these cells is still poorly understood, particularly in a situation where the antigen will be presented only in adult life. Here, we generated a transgenic mouse model in which keratinocytes exclusively present a myelin basic protein (MBP) peptide covalently linked to the major histocompatibility complex class II β-chain, solely under inflammatory conditions. In these mice, inflammation caused by epicutaneous contact sensitizer treatment resulted in keratinocyte-mediated expansion of MBP-specific CD4(+) T cells in the skin. Moreover, repeated contact sensitizer application preceding a systemic MBP immunization reduced the reactivity of the respective CD4(+) T cells and lowered the symptoms of the resulting experimental autoimmune encephalomyelitis. This downregulation was CD4(+) T-cell-mediated and dependent on the presence of the immune modulator Dickkopf-3. Thus, presentation of a neo self-antigen by keratinocytes in the inflamed, adult skin can modulate CD4(+) T-cell auto-aggression at a distal organ. PMID:25835957

  2. Sulforaphane induces phase II detoxication enzymes in mouse skin and prevents mutagenesis induced by a mustard gas analog

    Energy Technology Data Exchange (ETDEWEB)

    Abel, E.L. [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957 (United States); Boulware, S. [Division of Pharmacy and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute, 1400 Barbara Jordan Blvd., Austin, TX 78723 (United States); Fields, T.; McIvor, E.; Powell, K.L. [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957 (United States); DiGiovanni, J.; Vasquez, K.M. [Division of Pharmacy and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute, 1400 Barbara Jordan Blvd., Austin, TX 78723 (United States); MacLeod, M.C., E-mail: mcmacleod@mdanderson.org [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957 (United States)

    2013-02-01

    Mustard gas, used in chemical warfare since 1917, is a mutagenic and carcinogenic agent that produces severe dermal lesions for which there are no effective therapeutics; it is currently seen as a potential terrorist threat to civilian populations. Sulforaphane, found in cruciferous vegetables, is known to induce enzymes that detoxify compounds such as the sulfur mustards that react through electrophilic intermediates. Here, we observe that a single topical treatment with sulforaphane induces mouse epidermal levels of the regulatory subunit of glutamate-cysteine ligase, the rate-limiting enzyme in glutathione biosynthesis, and also increases epidermal levels of reduced glutathione. Furthermore, a glutathione S-transferase, GSTA4, is also induced in mouse skin by sulforaphane. In an in vivo model in which mice are given a single mutagenic application of the sulfur mustard analog 2-(chloroethyl) ethyl sulfide (CEES), we now show that therapeutic treatment with sulforaphane abolishes the CEES-induced increase in mutation frequency in the skin, measured four days after exposure. Sulforaphane, a natural product currently in clinical trials, shows promise as an effective therapeutic against mustard gas. -- Highlights: ► Sulforaphane induces increased levels of glutathione in mouse skin. ► Sulforaphane induces increased levels of GSTA4 in mouse skin. ► Sulforaphane, applied after CEES-treatment, completely abolishes CEES-mutagenesis. ► The therapeutic effect may suggest a long biological half-life for CEES in vivo.

  3. Aloe arborescens extract inhibits TPA-induced ear oedema, putrescine increase and tumour promotion in mouse skin.

    Science.gov (United States)

    Shimpo, Kan; Ida, Chikako; Chihara, Takeshi; Beppu, Hidehiko; Kaneko, Takaaki; Kuzuya, Hiroshi

    2002-08-01

    The ethyl acetate extract of the acetone-soluble Aloe arborescens fraction was found to inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear oedema, putrescine increase and tumour promotion in mouse skin. Chromatographic analyses of this extract revealed that phenolic compounds such as aloenin, barbaloin and isobarbaloin could be useful as cancer chemopreventive agents against tumour promotion. PMID:12203274

  4. Effect of olive and sunflower seed oil on the adult skin barrier: implications for neonatal skin care.

    Science.gov (United States)

    Danby, Simon G; AlEnezi, Tareq; Sultan, Amani; Lavender, Tina; Chittock, John; Brown, Kirsty; Cork, Michael J

    2013-01-01

    Natural oils are advocated and used throughout the world as part of neonatal skin care, but there is an absence of evidence to support this practice. The goal of the current study was to ascertain the effect of olive oil and sunflower seed oil on the biophysical properties of the skin. Nineteen adult volunteers with and without a history of atopic dermatitis were recruited into two randomized forearm-controlled mechanistic studies. The first cohort applied six drops of olive oil to one forearm twice daily for 5 weeks. The second cohort applied six drops of olive oil to one forearm and six drops of sunflower seed oil to the other twice daily for 4 weeks. The effect of the treatments was evaluated by determining stratum corneum integrity and cohesion, intercorneocyte cohesion, moisturization, skin-surface pH, and erythema. Topical application of olive oil for 4 weeks caused a significant reduction in stratum corneum integrity and induced mild erythema in volunteers with and without a history of atopic dermatitis. Sunflower seed oil preserved stratum corneum integrity, did not cause erythema, and improved hydration in the same volunteers. In contrast to sunflower seed oil, topical treatment with olive oil significantly damages the skin barrier, and therefore has the potential to promote the development of, and exacerbate existing, atopic dermatitis. The use of olive oil for the treatment of dry skin and infant massage should therefore be discouraged. These findings challenge the unfounded belief that all natural oils are beneficial for the skin and highlight the need for further research.

  5. Effect of olive and sunflower seed oil on the adult skin barrier: implications for neonatal skin care.

    Science.gov (United States)

    Danby, Simon G; AlEnezi, Tareq; Sultan, Amani; Lavender, Tina; Chittock, John; Brown, Kirsty; Cork, Michael J

    2013-01-01

    Natural oils are advocated and used throughout the world as part of neonatal skin care, but there is an absence of evidence to support this practice. The goal of the current study was to ascertain the effect of olive oil and sunflower seed oil on the biophysical properties of the skin. Nineteen adult volunteers with and without a history of atopic dermatitis were recruited into two randomized forearm-controlled mechanistic studies. The first cohort applied six drops of olive oil to one forearm twice daily for 5 weeks. The second cohort applied six drops of olive oil to one forearm and six drops of sunflower seed oil to the other twice daily for 4 weeks. The effect of the treatments was evaluated by determining stratum corneum integrity and cohesion, intercorneocyte cohesion, moisturization, skin-surface pH, and erythema. Topical application of olive oil for 4 weeks caused a significant reduction in stratum corneum integrity and induced mild erythema in volunteers with and without a history of atopic dermatitis. Sunflower seed oil preserved stratum corneum integrity, did not cause erythema, and improved hydration in the same volunteers. In contrast to sunflower seed oil, topical treatment with olive oil significantly damages the skin barrier, and therefore has the potential to promote the development of, and exacerbate existing, atopic dermatitis. The use of olive oil for the treatment of dry skin and infant massage should therefore be discouraged. These findings challenge the unfounded belief that all natural oils are beneficial for the skin and highlight the need for further research. PMID:22995032

  6. Skin.

    Science.gov (United States)

    Mancini, Anthony J

    2004-04-01

    Human skin provides a barrier between the host and the physical, chemical, and biological environment. It is also a potential portal of entry for hazardous or infectious agents and a potential target of environmental toxins. Cutaneous vulnerability may take on many forms in the embryo, infant, child, and adolescent. Teratogenic agents may occasionally target skin, as appreciated in the proposed association of the antithyroid medication methimazole, with the congenital malformation known as aplasia cutis congenita. Percutaneous absorption of topically applied substances and the potential for resultant drug toxicities are important considerations in the child. Many topical agents have been associated with systemic toxicity, including alcohol, hexachlorophene, iodine-containing compounds, eutectic mixture of local anesthetics, and lindane. Percutaneous toxicity is of greatest concern in the premature infant, in whom immaturity of the epidermal permeability barrier results in disproportionately increased absorption. Immature drug metabolism capabilities may further contribute to the increased risk in this population. Ultraviolet (UV) radiation exposure, which increases an individual's risk of cutaneous carcinogenesis, may be a particularly significant risk factor when it occurs during childhood. The "critical period hypothesis" suggests that UV exposure early in life increases the risk of eventual development of malignant melanoma. Other risk factors for malignant melanoma may include severe sunburns during childhood, intense intermittent UV exposure, and increased susceptibility of pediatric melanocytes to UV-induced DNA damage. Last, percutaneous exposure to environmental toxins and chemicals, such as insecticides and polychlorinated biphenyls, may differ between children and adults for several reasons, including behavioral patterns, anatomic and physiologic variations, and developmental differences of vital organs. PMID:15060207

  7. Thymoquinone inhibits phorbol ester-induced activation of NF-κB and expression of COX-2, and induces expression of cytoprotective enzymes in mouse skin in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Kundu, Joydeb Kumar [College of Pharmacy, Keimyung University, Daegu 704-701 (Korea, Republic of); Liu, Lijia; Shin, Jun-Wan [Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul 151-742 (Korea, Republic of); Surh, Young-Joon, E-mail: surh@plaza.snu.ac.kr [Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul 151-742 (Korea, Republic of); Cancer Research Institute, Seoul National University, Seoul 110-799 (Korea, Republic of)

    2013-09-06

    Highlights: •Thymoquinone inhibits phorbol ester-induced COX-2 expression in mouse skin. •Thymoquinone attenuates phosphorylation of IκBα and DNA binding of NF-κB in mouse skin. •Thymoquinone inhibits phosphorylation of p38 MAP kinase, JNK and Akt in mouse skin. •Thymoquinone induces the expression of cytoprotective proteins in mouse skin. -- Abstract: Thymoquinone (TQ), the active ingredient of Nigella sativa, has been reported to possess anti-inflammatory and chemopreventive properties. The present study was aimed at elucidating the molecular mechanisms of anti-inflammatory and antioxidative activities of thymoquinone in mouse skin. Pretreatment of female HR-1 hairless mouse skin with TQ attenuated 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced expression of cyclooxygenase-2 (COX-2). TQ diminished nuclear translocation and the DNA binding of nuclear factor-kappaB (NF-κB) via the blockade of phosphorylation and subsequent degradation of IκBα in TPA-treated mouse skin. Pretreatment with TQ attenuated the phosphorylation of Akt, c-Jun-N-terminal kinase and p38 mitogen-activated protein kinase, but not that of extracellular signal-regulated kinase-1/2. Moreover, topical application of TQ induced the expression of heme oxygenase-1, NAD(P)H-quinoneoxidoreductase-1, glutathione-S-transferase and glutamate cysteine ligase in mouse skin. Taken together, the inhibitory effects of TQ on TPA-induced COX-2 expression and NF-κB activation, and its ability to induce the expression of cytoprotective proteins provide a mechanistic basis of anti-inflammatory and antioxidative effects of TQ in hairless mouse skin.

  8. KIT D816V mutation-positive cell fractions in lesional skin biopsies from adults with systemic mastocytosis

    DEFF Research Database (Denmark)

    Kielsgaard Kristensen, Thomas; Broesby-Olsen, Sigurd; Vestergaard, Hanne;

    2013-01-01

    Most adults with systemic mastocytosis (SM) carry the somatic KIT D816V mutation, but the occurrence of the mutation in lesional skin remains to be characterized.......Most adults with systemic mastocytosis (SM) carry the somatic KIT D816V mutation, but the occurrence of the mutation in lesional skin remains to be characterized....

  9. Mechanisms of action of okadaic acid class tumor promoters on mouse skin

    Energy Technology Data Exchange (ETDEWEB)

    Fujiki, Hirota; Suganuma, Masami; Yoshizawa, Seiji; Nishiwaki, Shinji; Winyar, Boonsong (National Cancer Center Research Inst., Tokyo (Japan)); Sugimura, Takashi (National Cancer Center, Tokyo (Japan))

    1991-06-01

    Okadaic acid, dinophysistoxin-1 (35-methylokadaic acid), and calyculin A are the okadaic acid class of non-12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoters, which do not bind to the phorbol ester receptors in cell membranes or activate protein kinase C in vitro. They have potent tumor-promoting activities on mouse skin, as strong as TPA-type tumor promoters, such as TPA, teleocidin, and aplysiatoxin. DNA samples isolated from tumors induced by dimethylbenz(a)anthracene and each of the okadaic acid class tumor promoters had the same mutation at the second nucleotide of codon 61 (CAA to CTA) in the c-H-ras gene. Okadaic acid receptors, protein phosphatases 1 and 2A, are present in the particulate as well as cytosolic fractions of various mouse tissues. The apparent activation of protein kinases by the okadaic acid class tumor promoters, after their incubation with {sup 32}P-ATP, protein kinases, and protein phosphatases, was observed. This activation was caused by inhibition of protein phosphatases 1 and 2A by the okadaic acid class tumor promoters. Treatment of primary human fibroblasts and human keratinocytes with the okadaic acid class tumor promoters induced the hyperphosphorylation of a 60-k-Da protein in nuclear and cytosolic fractions, due to the inhibition of protein phosphatases. The 60-kDa protein is a proteolytic fragment of nucleolin, a major nonhistone protein and is designated as N-60. The mechanisms of action of the okadaic acid class tumor promoters are discussed with emphasis on the inhibition of protein phosphatase activity.

  10. Multimodality pH imaging in a mouse dorsal skin fold window chamber model

    Science.gov (United States)

    Leung, Hui Min; Schafer, Rachel; Pagel, Mark M.; Robey, Ian F.; Gmitro, Arthur F.

    2013-03-01

    Upregulate levels of expression and activity of membrane H+ ion pumps in cancer cells drives the extracellular pH (pHe,) to values lower than normal. Furthermore, disregulated pH is indicative of the changes in glycolytic metabolism in tumor cells and has been shown to facilitate extracellular tissue remodeling during metastasis Therefore, measurement of pHe could be a useful cancer biomarker for diagnostic and therapy monitoring evaluation. Multimodality in-vivo imaging of pHe in tumorous tissue in a mouse dorsal skin fold window chamber (DSFWC) model is described. A custom-made plastic window chamber structure was developed that is compatible with both imaging optical and MR imaging modalities and provides a model system for continuous study of the same tissue microenvironment on multiple imaging platforms over a 3-week period. For optical imaging of pHe, SNARF-1 carboxylic acid is injected intravenously into a SCID mouse with an implanted tumor. A ratiometric measurement of the fluorescence signal captured on a confocal microscope reveals the pHe of the tissue visible within the window chamber. This imaging method was used in a preliminary study to evaluate sodium bicarbonate as a potential drug treatment to reverse tissue acidosis. For MR imaging of pHe the chemical exchange saturation transfer (CEST) was used as an alternative way of measuring pHe in a DSFWC model. ULTRAVIST®, a FDA approved x-ray/CT contrast agent has been shown to have a CEST effect that is pH dependent. A ratiometric analysis of water saturation at 5.6 and 4.2 ppm chemical shift provides a means to estimate the local pHe.

  11. Staphylococcal Scalded Skin Syndrome: Criteria for Differential Diagnosis from Lyell's Syndrome. Two Cases in Adult Patients

    OpenAIRE

    Napoli, B.; D'Arpa, N.; D'Amelio, L.; S. Chimenti; Pileri, D.; Accardo-Palumbo, A.; F. Conte

    2006-01-01

    A review of the relative international literature of the last few years is followed by a description of two cases of staphylococcal scalded skin syndrome in adults. As in both cases the initial diagnosis was that of Lyell's syndrome, the main criteria for the differential diagnosis of the two pathologies are considered in order to permit specific and effective treatment.

  12. In vivo characterization of early-stage radiation skin injury in a mouse model by two-photon microscopy.

    Science.gov (United States)

    Jang, Won Hyuk; Shim, Sehwan; Wang, Taejun; Yoon, Yeoreum; Jang, Won-Suk; Myung, Jae Kyung; Park, Sunhoo; Kim, Ki Hean

    2016-01-01

    Ionizing radiation (IR) injury is tissue damage caused by high energy electromagnetic waves such as X-ray and gamma ray. Diagnosis and treatment of IR injury are difficult due to its characteristics of clinically latent post-irradiation periods and the following successive and unpredictable inflammatory bursts. Skin is one of the many sensitive organs to IR and bears local injury upon exposure. Early-stage diagnosis of IR skin injury is essential in order to maximize treatment efficiency and to prevent the aggravation of IR injury. In this study, early-stage changes of the IR injured skin at the cellular level were characterized in an in vivo mouse model by two-photon microscopy (TPM). Various IR doses were applied to the mouse hind limbs and the injured skin regions were imaged daily for 6 days after IR irradiation. Changes in the morphology and distribution of the epidermal cells and damage of the sebaceous glands were observed before clinical symptoms. These results showed that TPM is sensitive to early-stage changes of IR skin injury and may be useful for its diagnosis. PMID:26755422

  13. Multisystem Langerhans Cell Histiocytosis in Adults Revealed by Skin Lesions.

    Science.gov (United States)

    Atarguine, Hanane; Hocar, Ouafa; Oussmane, Samia; Mouafik, Sara Batoul; Hamdaoui, Abderrachid; Hafiane, Hanan; Belbaraka, Rhizlane; Akhdari, Nadia; Amal, Said

    2016-01-01

    A 37-year-old woman with no remarkable medical or family history presented with papules and vesicles on an erythematous background involving the neck, sacrum, and folds (postauricular, axillary, inguinal, and under the breasts) (Figure 1). During the previous year, she was treated with local and systemic antifungals without improvement. Her history included a secondary amenorrhea, polydipsia, and polyuria (6 L/d) that started 2 years prior. Physical examination revealed chronic bilateral purulent otorrhea with thick eardrums. Histologic examination of skin biopsy revealed a highly suggestive appearance of multisystem Langerhans cell histiocytosis (LCH) with immunohistochemistry (anti-PS100 and anti-CD1a), which were positive (Figure 2A and 2B). Pituitary magnetic resonance imaging showed a thickening of the pituitary stalk in relation to a location histiocytic (Figure 3). Bone gaps were objectified on two radiographic tibial diaphyseal. Results from computed tomography (CT) scan showed a magma coelio mesenteric, axillary, and inguinal lymph nodes. PMID:27319965

  14. Antiinflammatory and Antiphotodamaging Effects of Ergostatrien-3β-ol, Isolated from Antrodia camphorata, on Hairless Mouse Skin.

    Science.gov (United States)

    Kuo, Yueh-Hsiung; Lin, Tzu-Yu; You, Ya-Jhen; Wen, Kuo-Ching; Sung, Ping-Jyun; Chiang, Hsiu-Mei

    2016-01-01

    Ergostatrien-3β-ol (EK100), isolated from the submerged whole broth of Antrodia camphorata, has antidiabetic, hyperlipidemic, and hepatoprotective activities. However, the antiphotodamage activity of EK100 has still not been revealed. Inflammation and collagen degradation contribute to skin photodamage and premature aging. In the present study, in vivo experiments were designed to investigate the antiinflammatory and antiphotodamaging activities of EK100 in hairless mice by physiological and histological analysis of the skin. Results indicated that topical application of EK100 (25 and 100 μM) for 10 weeks efficiently inhibited ultraviolet B (UVB)-induced wrinkle formation, erythema, and epidermal thickness in the mice skin. EK100 also restored UVB-induced collagen content reduction in hairless mice skin. In addition, the immunohistochemistry results indicated that EK100 significantly inhibited the UVB-induced expression of matrix metalloproteinase-1 (MMP-1), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and nuclear factor kappaB (NF-κB) in the mouse skin. The expression of these proteins was similar to the Normal group after 100 μM EK100 treatment. EK100 inhibited collagen degradation in the skin through MMP-1 inhibition and antiinflammation. EK100 significantly reduced the transepidermal water loss (TEWL), indicating that EK100 protected skin from UVB-induced damage. Our findings strongly suggest that EK100 has significant beneficial antiinflammatory and antiphotoaging activities and that EK100 can be developed as an antiphotodamaging agent. PMID:27626393

  15. Carcinogenicity and co-carcinogenicity studies on propoxur in mouse skin.

    Science.gov (United States)

    Shukla, Y; Baqar, S M; Mehrotra, N K

    1998-12-01

    Propoxur (2-isopropoxyphenyl methylcarbamate) is a widely used broad spectrum carbamate insecticide mainly used to control household pests. Propoxur exposure is reported to inhibit cholinesterase activity in rodents. Apart from other toxic effects, propoxur was found to possess tumorigenic activity in rats after oral administration. Propoxur does not produce tumours in mice or hamsters, or bladder hyperplasia in dogs and monkeys following oral feeding. In this set of investigations the complete carcinogenic, tumour initiating and promoting potential of propoxur was evaluated in male and female Swiss albino mice, since no information was available following dermal exposure of propoxur. The animals were exposed to propoxur through topical painting on the interscapular region at a dose of 100 mg/kg body weight. The results revealed that propoxur has tumour promoting potential on mouse skin following a two-stage initiation-promotion protocol, but it failed to induce the tumour(s) at a significant level, when tested for tumour initiating and complete carcinogenic property.

  16. Cerebellar stem cells do not produce neurons and astrocytes in adult mouse

    Energy Technology Data Exchange (ETDEWEB)

    Su, Xin; Guan, Wuqiang; Yu, Yong-Chun; Fu, Yinghui, E-mail: fuyh@fudan.edu.cn

    2014-07-18

    Highlights: • No new neurons and astrocytes are generated in adult mouse cerebellum. • Very few mash1{sup +} or nestin{sup +} stem cells exist, and most of them are quiescent. • Cell proliferation rate is diversified among cerebellar regions and decreases over time. - Abstract: Although previous studies implied that cerebellar stem cells exist in some adult mammals, little is known about whether these stem cells can produce new neurons and astrocytes. In this study by bromodeoxyuridine (BrdU) intraperitoneal (i.p.) injection, we found that there are abundant BrdU{sup +} cells in adult mouse cerebellum, and their quantity and density decreases significantly over time. We also found cell proliferation rate is diversified in different cerebellar regions. Among these BrdU{sup +} cells, very few are mash1{sup +} or nestin{sup +} stem cells, and the vast majority of cerebellar stem cells are quiescent. Data obtained by in vivo retrovirus injection indicate that stem cells do not produce neurons and astrocytes in adult mouse cerebellum. Instead, some cells labeled by retrovirus are Iba1{sup +} microglia. These results indicate that very few stem cells exist in adult mouse cerebellum, and none of these stem cells contribute to neurogenesis and astrogenesis under physiological condition.

  17. Cerebellar stem cells do not produce neurons and astrocytes in adult mouse

    International Nuclear Information System (INIS)

    Highlights: • No new neurons and astrocytes are generated in adult mouse cerebellum. • Very few mash1+ or nestin+ stem cells exist, and most of them are quiescent. • Cell proliferation rate is diversified among cerebellar regions and decreases over time. - Abstract: Although previous studies implied that cerebellar stem cells exist in some adult mammals, little is known about whether these stem cells can produce new neurons and astrocytes. In this study by bromodeoxyuridine (BrdU) intraperitoneal (i.p.) injection, we found that there are abundant BrdU+ cells in adult mouse cerebellum, and their quantity and density decreases significantly over time. We also found cell proliferation rate is diversified in different cerebellar regions. Among these BrdU+ cells, very few are mash1+ or nestin+ stem cells, and the vast majority of cerebellar stem cells are quiescent. Data obtained by in vivo retrovirus injection indicate that stem cells do not produce neurons and astrocytes in adult mouse cerebellum. Instead, some cells labeled by retrovirus are Iba1+ microglia. These results indicate that very few stem cells exist in adult mouse cerebellum, and none of these stem cells contribute to neurogenesis and astrogenesis under physiological condition

  18. Optical Monitoring of Living Nerve Terminal Labeling in Hair Follicle Lanceolate Endings of the Ex Vivo Mouse Ear Skin

    OpenAIRE

    Bewick, Guy S.; Banks, Robert W.

    2016-01-01

    A novel dissection and recording technique is described for optical monitoring staining and de-staining of lanceolate terminals surrounding hair follicles in the skin of the mouse pinna. The preparation is simple and relatively fast, reliably yielding extensive regions of multiple labeled units of living nerve terminals to study uptake and release of styryl pyridinium dyes extensively used in studies of vesicle recycling. Subdividing the preparations before labeling allows test vs. control co...

  19. Loss of Endogenous Interleukin-12 Activates Survival Signals in Ultraviolet-Exposed Mouse Skin and Skin Tumors

    Directory of Open Access Journals (Sweden)

    Syed M. Meeran

    2009-09-01

    Full Text Available Interleukin-12 (IL-12-deficiency promotes photocarcinogenesis in mice; however, the molecular mechanisms underlying this effect have not been fully elucidated. Here, we report that long-term exposure to ultraviolet (UV radiation resulted in enhancement of the levels of cell survival kinases, such as phosphatidylinositol 3-kinase (PI3K, Akt (Ser473, p-ERK1/2, and p-p38 in the skin of IL-12p40 knockout (IL-12 KO mice compared with the skin of wild-type mice. UV-induced activation of nuclear factor-κB (NF-κB/p65 in the skin of IL-12 KO mice was also more prominent. The levels of NF-κB-targeted proteins, such as proliferating cell nuclear antigen (PCNA, cyclooxygenase-2, cyclin D1, and inducible nitric oxide synthase, were higher in the UV-exposed skin of IL-12 KO mice than the UV-exposed skin of wild types. In short-term UV irradiation experiments, subcutaneous treatment of IL-12 KO mice with recombinant IL-12 (rIL-12 or topical treatment with oridonin, an inhibitor of NF-κB, resulted in the inhibition of UV-induced increases in the levels of PCNA, cyclin D1, and NF-κB compared with non-rIL-12- or non-oridonin-treated IL-12 KO mice. UV-induced skin tumors of IL-12 KO mice had higher levels of PI3K, p-Akt (Ser473, p-ERK1/2, p-p38, NF-κB, and PCNA and fewer apoptotic cells than skin tumors of wild types. Together, these data suggest that the loss of endogenous IL-12 activates survival signals in UV-exposed skin and that may lead to the enhanced photocarcinogenesis in mice.

  20. Combined effect of cyclin D3 expression and abrogation of cyclin D1 prevent mouse skin tumor development

    Science.gov (United States)

    Wang, Xian; Sistrunk, Christopher; Miliani de Marval, Paula L; Kim, Yongbaek

    2012-01-01

    We have previously demonstrated that ras-mediated skin tumorigenesis depends on signaling pathways that act preferentially through cyclin D1 and D2. Interestingly, the expression of cyclin D3 inhibits skin tumor development, an observation that conflicts with the oncogenic role of D-type cyclins in the mouse epidermis. Here, we show that simultaneous up and downregulation of particular members of the D-type cyclin family is a valuable approach to reduce skin tumorigenesis. We developed the K5D3/cyclin D1−/− compound mouse, which overexpresses cyclin D3 but lacks expression of cyclin D1 in the skin. Similar to K5D3 transgenic mice, keratinocytes from K5D3/cyclin D1−/− compound mice show a significant reduction of cyclin D2 levels. Therefore, this model allows us to determine the effect of cyclin D3 expression when combined with reduced or absent expression of the remaining two members of the D-type cyclin family in mouse epidermis. Our data show that induced expression of cyclin D3 compensates for the reduced level of cyclin D1 and D2, resulting in normal keratinocyte proliferation. However, simultaneous ablation of cyclin D1 and downregulation of cyclin D2 via cyclin D3 expression resulted in a robust reduction in ras-mediated skin tumorigenesis. We conclude that modulation of the levels of particular members of the D-type cyclin family could be useful to inhibit tumor development and, in particular, ras-mediated tumorigenesis. PMID:22214766

  1. Liver Repopulation and Correction of Metabolic Liver Disease by Transplanted Adult Mouse Pancreatic Cells

    OpenAIRE

    Wang, Xin; Al-Dhalimy, Muhsen; Lagasse, Eric; Finegold, Milton; Grompe, Markus

    2001-01-01

    The emergence of cells with hepatocellular properties in the adult pancreas has been described in several experimental models. To determine whether adult pancreas contains cells that can give rise to therapeutically useful and biochemically normal hepatocytes, we transplanted suspensions of wild-type mouse pancreatic cells into syngeneic recipients deficient in fumarylacetoacetate hydrolase and manifesting tyrosinemia. Four of 34 (12%) mutant mice analyzed were fully rescued by donor-derived ...

  2. Retinoic acid fails to reverse emphysema in adult mouse models

    OpenAIRE

    Fujita, M; Ye, Q.; Ouchi, H.; Nakashima, N; Hamada, N; Hagimoto, N; Kuwano, K.; Mason, R.; Nakanishi, Y

    2004-01-01

    Methods: The models used were an elastase induced emphysema model for acute alveolar destruction and a tumour necrosis factor (TNF)-α transgenic mouse which exhibits chronic air space enlargement, loss of elastic recoil, increased lung volume, and pulmonary hypertension comparable to human pulmonary emphysema. All-trans-retinoic acid (2 mg/kg) was injected for 12 successive days after the establishment of emphysema. The effects of treatment were evaluated using physiological and morphometric ...

  3. Cell death induced on cell cultures and nude mouse skin by non-thermal, nanosecond-pulsed generated plasma.

    Directory of Open Access Journals (Sweden)

    Arnaud Duval

    Full Text Available Non-thermal plasmas are gaseous mixtures of molecules, radicals, and excited species with a small proportion of ions and energetic electrons. Non-thermal plasmas can be generated with any high electro-magnetic field. We studied here the pathological effects, and in particular cell death, induced by nanosecond-pulsed high voltage generated plasmas homogeneously applied on cell cultures and nude mouse skin. In vitro, Jurkat cells and HMEC exhibited apoptosis and necrosis, in dose-dependent manner. In vivo, on nude mouse skin, cell death occurred for doses above 113 J/cm(2 for the epidermis, 281 J/cm(2 for the dermis, and 394 J/cm(2 for the hypodermis. Using electron microscopy, we characterized apoptosis for low doses and necrosis for high doses. We demonstrated that these effects were not related to thermal, photonic or pH variations, and were due to the production of free radicals. The ability of cold plasmas to generate apoptosis on cells in suspension and, without any sensitizer, on precise skin areas, opens new fields of application in dermatology for extracorporeal blood cell treatment and the eradication of superficial skin lesions.

  4. Expression analysis of the mouse S100A7/psoriasin gene in skin inflammation and mammary tumorigenesis

    International Nuclear Information System (INIS)

    The human psoriasin (S100A7) gene has been implicated in inflammation and tumor progression. Implementation of a mouse model would facilitate further investigation of its function, however little is known of the murine psoriasin gene. In this study we have cloned the cDNA and characterized the expression of the potential murine ortholog of human S100A7/psoriasin in skin inflammation and mammary tumorigenesis. On the basis of chromosomal location, phylogenetic analysis, amino acid sequence similarity, conservation of a putative Jab1-binding motif, and similarities of the patterns of mouse S100A7/psoriasin gene expression (measured by RT-PCR and in-situ hybridization) with those of human S100A7/psoriasin, we propose that mouse S100A7/psoriasin is the murine ortholog of human psoriasin/S100A7. Although mouse S100A7/psoriasin is poorly conserved relative to other S100 family members, its pattern of expression parallels that of the human psoriasin gene. In murine skin S100A7/psoriasin was significantly upregulated in relation to inflammation. In murine mammary gland expression is also upregulated in mammary tumors, where it is localized to areas of squamous differentiation. This mirrors the context of expression in human tumor types where both squamous and glandular differentiation occur, including cervical and lung carcinomas. Additionally, mouse S100A7/psoriasin possesses a putative Jab1 binding motif that mediates many downstream functions of the human S100A7 gene. These observations and results support the hypothesis that the mouse S100A7 gene is structurally and functionally similar to human S100A7 and may offer a relevant model system for studying its normal biological function and putative role in tumor progression

  5. Propagation of Adult SSCs: From Mouse to Human

    OpenAIRE

    Martin, Laura A.; Marco Seandel

    2013-01-01

    Adult spermatogonial stem cells (SSCs) represent a distinctive source of stem cells in mammals for several reasons. First, by giving rise to spermatogenesis, SSCs are responsible for the propagation of a father’s genetic material. As such, autologous SSCs have been considered for treatment of infertility and other purposes, including correction of inherited disorders. Second, adult spermatogonia can spontaneously produce embryonic-like stem cells in vitro, which could be used a...

  6. Induction of active melanocytes in mouse skin by carcinogens: a new method for detection of skin carcinogens.

    Science.gov (United States)

    Iwata, K; Inui, N; Takeuchi, T

    1981-01-01

    Application of potent skin carcinogens, such as 7,12-dimethylbenz[a]anthracene, 3-methylcholanthrene, benzo[a]pyrene and 4-nitroquinoline-1-oxide, induced numerous dihydroxyphenylalanine (dopa)-positive cells in the interfollicular epidermis of C57BL/6 mice in a dose- and time-dependent fashion. Chrysene, a weak skin carcinogen, and croton oil, a tumor promoter, also induced 3--4 times more dopa-positive cells than acetone. Liver carcinogens, such as 3'-methyl-4-dimethylaminoazobenzene and N-2-acetylaminofluorene, and non-carcinogenic aromatic hydrocarbons, such as anthracene, fluoranthene, fluorene and pyrene, did not induce increase in these cells. These results indicate that increase in the number of dopa-positive cells after application of chemicals is well correlated with the abilities of these compounds to induce skin carcinogenesis and suppress sebaceous glands. PMID:7273337

  7. Molecular properties of adult mouse gastric and intestinal epithelial progenitors in their niches

    DEFF Research Database (Denmark)

    Giannakis, Marios; Stappenbeck, Thaddeus S; Mills, Jason C;

    2006-01-01

    We have sequenced 36,641 expressed sequence tags from laser capture microdissected adult mouse gastric and small intestinal epithelial progenitors, obtaining 4031 and 3324 unique transcripts, respectively. Using Gene Ontology (GO) terms, each data set was compared with cDNA libraries from intact...

  8. Fictive locomotion in the adult decerebrate and spinal mouse in vivo

    DEFF Research Database (Denmark)

    Meehan, Claire Francesca; Grøndahl, Lillian; Nielsen, Jens Bo;

    2012-01-01

    that it is possible to evoke fictive locomotion in the adult decerebrate mouse in vivo using L-3,4-Dihydroxyphenylalanine methyl ester hydrochloride (L-DOPA) and 5-hydroxytryptophan (5HTP) following injection of the monoaminoxiadase inhibitor Nialamide. We investigate the effects of afferent stimulation...

  9. CDK2 Activation in Mouse Epidermis Induces Keratinocyte Proliferation but Does Not Affect Skin Tumor Development

    Science.gov (United States)

    Macias, Everardo; Miliani de Marval, Paula L.; De Siervi, Adriana; Conti, Claudio J.; Senderowicz, Adrian M.; Rodriguez-Puebla, Marcelo L.

    2008-01-01

    It has been widely assumed that elevated CDK2 kinase activity plays a contributory role in tumorigenesis. We have previously shown that mice overexpressing CDK4 under control of the keratin 5 promoter (K5CDK4 mice) develop epidermal hyperplasia and increased susceptibility to squamous cell carcinomas. In this model, CDK4 overexpression results in increased CDK2 activity associated with the noncatalytic function of CDK4, sequestration of p21Cip1 and p27Kip1. Furthermore, we have shown that ablation of Cdk2 reduces Ras-Cdk4 tumorigenesis, suggesting that increased CDK2 activity plays an important role in Ras-mediated tumorigenesis. To investigate this hypothesis, we generated two transgenic mouse models of elevated CDK2 kinase activity, K5Cdk2 and K5Cdk4D158N mice. The D158N mutation blocks CDK4 kinase activity without interfering with its binding capability. CDK2 activation via overexpression of CDK4D158N, but not of CDK2, resulted in epidermal hyperplasia. We observed elevated levels of p21Cip1 in K5Cdk2, but not in K5Cdk4D158N, epidermis, suggesting that CDK2 overexpression elicits a p21Cip1 response to maintain keratinocyte homeostasis. Surprisingly, we found that neither CDK2 overexpression nor the indirect activation of CDK2 enhanced skin tumor development. Thus, although the indirect activation of CDK2 is sufficient to induce keratinocyte hyperproliferation, activation of CDK2 alone does not induce malignant progression in Ras-mediated tumorigenesis. PMID:18599613

  10. Differential Features between Chronic Skin Inflammatory Diseases Revealed in Skin-Humanized Psoriasis and Atopic Dermatitis Mouse Models.

    Science.gov (United States)

    Carretero, Marta; Guerrero-Aspizua, Sara; Illera, Nuria; Galvez, Victoria; Navarro, Manuel; García-García, Francisco; Dopazo, Joaquin; Jorcano, Jose Luis; Larcher, Fernando; del Rio, Marcela

    2016-01-01

    Psoriasis and atopic dermatitis are chronic and relapsing inflammatory diseases of the skin affecting a large number of patients worldwide. Psoriasis is characterized by a T helper type 1 and/or T helper type 17 immunological response, whereas acute atopic dermatitis lesions exhibit T helper type 2-dominant inflammation. Current single gene and signaling pathways-based models of inflammatory skin diseases are incomplete. Previous work allowed us to model psoriasis in skin-humanized mice through proper combinations of inflammatory cell components and disruption of barrier function. Herein, we describe and characterize an animal model for atopic dermatitis using similar bioengineered-based approaches, by intradermal injection of human T helper type 2 lymphocytes in regenerated human skin after partial removal of stratum corneum. In this work, we have extensively compared this model with the previous and an improved version of the psoriasis model, in which T helper type 1 and/or T helper type 17 lymphocytes replace exogenous cytokines. Comparative expression analyses revealed marked differences in specific epidermal proliferation and differentiation markers and immune-related molecules, including antimicrobial peptides. Likewise, the composition of the dermal inflammatory infiltrate presented important differences. The availability of accurate and reliable animal models for these diseases will contribute to the understanding of the pathogenesis and provide valuable tools for drug development and testing. PMID:26763433

  11. Progression of mouse skin carcinogenesis is associated with increased ERα levels and is repressed by a dominant negative form of ERα.

    Directory of Open Access Journals (Sweden)

    Stella Logotheti

    Full Text Available Estrogen receptors (ER, namely ERα and ERβ, are hormone-activated transcription factors with an important role in carcinogenesis. In the present study, we aimed at elucidating the implication of ERα in skin cancer, using chemically-induced mouse skin tumours, as well as cell lines representing distinct stages of mouse skin oncogenesis. First, using immunohistochemical staining we showed that ERα is markedly increased in aggressive mouse skin tumours in vivo as compared to the papilloma tumours, whereas ERβ levels are low and become even lower in the aggressive spindle tumours of carcinogen-treated mice. Then, using the multistage mouse skin carcinogenesis model, we showed that ERα gradually increases during promotion and progression stages of mouse skin carcinogenesis, peaking at the most aggressive stage, whereas ERβ levels only slightly change throughout skin carcinogenesis. Stable transfection of the aggressive, spindle CarB cells with a dominant negative form of ERα (dnERα resulted in reduced ERα levels and reduced binding to estrogen responsive elements (ERE-containing sequences. We characterized two highly conserved EREs on the mouse ERα promoter through which dnERα decreased endogenous ERα levels. The dnERα-transfected CarB cells presented altered protein levels of cytoskeletal and cell adhesion molecules, slower growth rate and impaired anchorage-independent growth in vitro, whereas they gave smaller tumours with extended latency period of tumour onset in vivo. Our findings suggest an implication of ERα in the aggressiveness of spindle mouse skin cancer cells, possibly through regulation of genes affecting cell shape and adhesion, and they also provide hints for the effective targeting of spindle cancer cells by dnERα.

  12. Ascl3 marks adult progenitor cells of the mouse salivary gland.

    Science.gov (United States)

    Rugel-Stahl, Anastasia; Elliott, Marilyn E; Ovitt, Catherine E

    2012-05-01

    The Ascl3 transcription factor marks a subset of salivary gland duct cells present in the three major salivary glands of the mouse. In vivo, these cells generate both duct and secretory acinar cell descendants. Here, we have analyzed whether Ascl3-expressing cells retain this multipotent lineage potential in adult glands. Cells isolated from mouse salivary glands were cultured in vitro as non-adherent spheres. Lineage tracing of the Ascl3-expressing cells within the spheres demonstrates that Ascl3+ cells isolated from adult glands remain multipotent, generating both duct and acinar cell types in vitro. Furthermore, we demonstrate that the progenitor cells characterized by Keratin 5 expression are an independent population from Ascl3+ progenitor cells. We conclude that the Ascl3+ cells are intermediate lineage-restricted progenitor cells of the adult salivary glands.

  13. Comparison of impedance measurements near the skin of newborns and adults.

    Science.gov (United States)

    Amm, Bruce; Kao, Tzu-Jen; Newell, Jonathan; Isaacson, David; Saulnier, Gary; Shoudy, David; Boverman, Greg; Sahni, Rakesh; Weindler, Marilyn; Chong, David; DiBardino, David; Davenport, David; Ashe, Jeffrey

    2016-06-01

    Electrical impedance tomography (EIT) is a non-invasive imaging technology that has been extensively studied for monitoring lung function of neonatal and adult subjects, especially in neonatal intensive care unit (NICU) and intensive care unit (ICU) environments. The sources of the total impedance in these applications include internal organs, near-boundary tissues, electrode-skin impedance, electrodes and conducting wires. This total impedance must be considered for system design and setting voltage gain since it will contribute to the measured voltage. To adapt a single instrument for use on infants and adults, we studied the difference between the impedance near the skin in both classes of patients. We used a simultaneous multi-source EIT (SMS-EIT) system to make impedance measurements. Characteristic resistance was calculated for two different current patterns: one that is more sensitive to boundary region impedance and another that is more sensitive to interior changes. We present ratios of these resistances to assess the relative contribution of near-skin effects to the overall impedance. Twenty adult ICU subjects (10 male, 10 female, age: 49.05  ±  16.32 years (mean  ±  standard deviation)) and 45 neonates (23 male, 22 female, gestational age: 37.67  ±  2.11 weeks, postnatal age, 2.56  ±  2.67 d) were studied at Columbia University Medical Center. Impedance measurements at 10 kHz were collected for approximately one hour from each subject. The characteristic resistance ratio for each subject was computed and analyzed. The result shows the impedance at or near the skin of newborns is significantly higher than in adult subjects. PMID:27203362

  14. Skin Regeneration in Adult Axolotls: A Blueprint for Scar-Free Healing in Vertebrates

    OpenAIRE

    Seifert, Ashley W.; Monaghan, James R; Voss, S. Randal; Maden, Malcolm

    2012-01-01

    While considerable progress has been made towards understanding the complex processes and pathways that regulate human wound healing, regenerative medicine has been unable to develop therapies that coax the natural wound environment to heal scar-free. The inability to induce perfect skin regeneration stems partly from our limited understanding of how scar-free healing occurs in a natural setting. Here we have investigated the wound repair process in adult axolotls and demonstrate that they ar...

  15. Predicting skin deficits through surface area measurements in ear reconstruction and adult ear surface area norms.

    Science.gov (United States)

    Yazar, Memet; Sevim, Kamuran Zeynep; Irmak, Fatih; Yazar, Sevgi Kurt; Yeşilada, Ayşin Karasoy; Karşidağğ, Semra Hacikerim; Tatlidede, Hamit Soner

    2013-07-01

    Ear reconstruction is one of the most challenging procedures in plastic surgery practice. Many studies and techniques have been described in the literature for carving a well-pronounced framework. However, just as important as the cartilage framework is the ample amount of delicate skin coverage of the framework. In this report, we introduce an innovative method of measuring the skin surface area of the auricle from a three-dimensional template created from the healthy ear.The study group consisted of 60 adult Turkish individuals who were randomly selected (30 men and 30 women). The participant ages ranged from 18 to 45 years (mean, 31.5 years), and they had no history of trauma or congenital anomalies. The template is created by dividing the ear into aesthetic subunits and using ImageJ software to estimate the necessary amount of total skin surface area required.Reconstruction of the auricle is a complicated process that requires experience and patience to provide the auricular details. We believe this estimate will shorten the learning curve for residents and surgeons interested in ear reconstruction and will help surgeons obtain adequate skin to drape over the well-sculpted cartilage frameworks by providing a reference list of total ear skin surface area measurements for Turkish men and women. PMID:23851770

  16. Cyclooxygenases in human and mouse skin and cultured human keratinocytes: association of COX-2 expression with human keratinocyte differentiation

    Science.gov (United States)

    Leong, J.; Hughes-Fulford, M.; Rakhlin, N.; Habib, A.; Maclouf, J.; Goldyne, M. E.

    1996-01-01

    Epidermal expression of the two isoforms of the prostaglandin H-generating cyclooxygenase (COX-1 and COX-2) was evaluated both by immunohistochemistry performed on human and mouse skin biopsy sections and by Western blotting of protein extracts from cultured human neonatal foreskin keratinocytes. In normal human skin, COX-1 immunostaining is observed throughout the epidermis whereas COX-2 immunostaining increases in the more differentiated, suprabasilar keratinocytes. Basal cell carcinomas express little if any COX-1 or COX-2 immunostaining whereas both isozymes are strongly expressed in squamous cell carcinomas deriving from a more differentiated layer of the epidermis. In human keratinocyte cultures, raising the extracellular calcium concentration, a recognized stimulus for keratinocyte differentiation, leads to an increased expression of both COX-2 protein and mRNA; expression of COX-1 protein, however, shows no significant alteration in response to calcium. Because of a recent report that failed to show COX-2 in normal mouse epidermis, we also looked for COX-1 and COX-2 immunostaining in sections of normal and acetone-treated mouse skin. In agreement with a previous report, some COX-1, but no COX-2, immunostaining is seen in normal murine epidermis. However, following acetone treatment, there is a marked increase in COX-1 expression as well as the appearance of significant COX-2 immunostaining in the basal layer. These data suggest that in human epidermis as well as in human keratinocyte cultures, the expression of COX-2 occurs as a part of normal keratinocyte differentiation whereas in murine epidermis, its constitutive expression is absent, but inducible as previously published.

  17. Long-term bezafibrate treatment improves skin and spleen phenotypes of the mtDNA mutator mouse.

    Directory of Open Access Journals (Sweden)

    Lloye M Dillon

    Full Text Available Pharmacological agents, such as bezafibrate, that activate peroxisome proliferator-activated receptors (PPARs and PPAR γ coactivator-1α (PGC-1α pathways have been shown to improve mitochondrial function and energy metabolism. The mitochondrial DNA (mtDNA mutator mouse is a mouse model of aging that harbors a proofreading-deficient mtDNA polymerase γ. These mice develop many features of premature aging including hair loss, anemia, osteoporosis, sarcopenia and decreased lifespan. They also have increased mtDNA mutations and marked mitochondrial dysfunction. We found that mutator mice treated with bezafibrate for 8-months had delayed hair loss and improved skin and spleen aging-like phenotypes. Although we observed an increase in markers of fatty acid oxidation in these tissues, we did not detect a generalized increase in mitochondrial markers. On the other hand, there were no improvements in muscle function or lifespan of the mutator mouse, which we attributed to the rodent-specific hepatomegaly associated with fibrate treatment. These results showed that despite its secondary effects in rodent's liver, bezafibrate was able to improve some of the aging phenotypes in the mutator mouse. Because the associated hepatomegaly is not observed in primates, long-term bezafibrate treatment in humans could have beneficial effects on tissues undergoing chronic bioenergetic-related degeneration.

  18. Curcumin Stimulates the Antioxidant Mechanisms in Mouse Skin Exposed to Fractionated γ-Irradiation

    OpenAIRE

    Ganesh Chandra Jagetia; Golgod Krishnamurthy Rajanikant

    2015-01-01

    Fractionated irradiation is one of the important radiotherapy regimens to treat different types of neoplasia. Despite of the immense therapeutic gains accrued by delivering fractionated irradiation to tumors, the radiation burden on skin increases significantly. Low doses of irradiation to skin adversely affect its molecular and metabolic status. The use of antioxidant/s may help to alleviate the radiation-induced changes in the skin and allow delivering a higher dose of radiation to attain b...

  19. Systemic morphine treatment induces changes in firing patterns and responses of nociceptive afferent fibers in mouse glabrous skin

    OpenAIRE

    Hogan, Dale; Baker, Alyssa L.; Morón, Jose A.; Carlton, Susan M.

    2013-01-01

    Patients receiving opioids for pain may experience decreased effectiveness of the drug and even abnormal pain sensitivity – either hyperalgesia and/or allodynia. We hypothesize that peripheral nociceptor hyperexcitability contributes to opioid-induced hyperalgesia and test this using an in vitro mouse glabrous skin-nerve preparation. Mice were injected i.p. with escalating doses of morphine (5, 8, 10, 15 mg/kg) or saline every 12 h for 48 h and sacrificed ~12 h following the last injection. R...

  20. Myeloid Cell Isolation from Mouse Skin and Draining Lymph Node Following Intradermal Immunization with Live Attenuated Plasmodium Sporozoites.

    Science.gov (United States)

    Mac-Daniel, Laura; Buckwalter, Matthew R; Gueirard, Pascale; Ménard, Robert

    2016-01-01

    Malaria infection begins when the sporozoite stage of Plasmodium is inoculated into the skin of a mammalian host through a mosquito bite. The highly motile parasite not only reaches the liver to invade hepatocytes and transform into erythrocyte-infective form. It also migrates into the skin and to the proximal lymph node draining the injection site, where it can be recognized and degraded by resident and/or recruited myeloid cells. Intravital imaging reported the early recruitment of brightly fluorescent Lys-GFP positive leukocytes in the skin and the interactions between sporozoites and CD11c(+) cells in the draining lymph node. We present here an efficient procedure to recover, identify and enumerate the myeloid cell subsets that are recruited to the mouse skin and draining lymph node following intradermal injection of immunizing doses of sporozoites in a murine model. Phenotypic characterization using multi-parametric flow cytometry provides a reliable assay to assess early dynamic cellular changes during inflammatory response to Plasmodium infection. PMID:27286053

  1. MicroRNA expression in the adult mouse central nervous system

    DEFF Research Database (Denmark)

    Bak, Mads; Silahtaroglu, Asli; Møller, Morten;

    2008-01-01

    distinct areas of the adult mouse central nervous system (CNS). Microarray profiling in combination with real-time RT-PCR and LNA (locked nucleic acid)-based in situ hybridization uncovered 44 miRNAs displaying more than threefold enrichment in the spinal cord, cerebellum, medulla oblongata, pons......, hypothalamus, hippocampus, neocortex, olfactory bulb, eye, and pituitary gland. These findings suggest that a large number of mouse CNS-expressed miRNAs may be associated with specific functions within these regions. Notably, more than 50% of the identified mouse CNS-enriched miRNAs showed different expression......RNA-related gene regulatory networks in the mammalian central nervous system. Udgivelsesdato: 2008-Mar...

  2. Resveratrol and black tea polyphenol combination synergistically suppress mouse skin tumors growth by inhibition of activated MAPKs and p53.

    Directory of Open Access Journals (Sweden)

    Jasmine George

    Full Text Available Cancer chemoprevention by natural dietary agents has received considerable importance because of their cost-effectiveness and wide safety margin. However, single agent intervention has failed to bring the expected outcome in clinical trials; therefore, combinations of chemopreventive agents are gaining increasing popularity. The present study aims to evaluate the combinatorial chemopreventive effects of resveratrol and black tea polyphenol (BTP in suppressing two-stage mouse skin carcinogenesis induced by DMBA and TPA. Resveratrol/BTP alone treatment decreased tumor incidence by ∼67% and ∼75%, while combination of both at low doses synergistically decreased tumor incidence even more significantly by ∼89% (p<0.01. This combination also significantly regressed tumor volume and number (p<0.01. Mechanistic studies revealed that this combinatorial inhibition was associated with decreased expression of phosphorylated mitogen-activated protein kinase family proteins: extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase 1/2, p38 and increased in total p53 and phospho p53 (Ser 15 in skin tissue/tumor. Treatment with combinations of resveratrol and BTP also decreased expression of proliferating cell nuclear antigen in mouse skin tissues/tumors than their solitary treatments as determined by immunohistochemistry. In addition, histological and cell death analysis also confirmed that resveratrol and BTP treatment together inhibits cellular proliferation and markedly induces apoptosis. Taken together, our results for the first time lucidly illustrate that resveratrol and BTP in combination impart better suppressive activity than either of these agents alone and accentuate that development of novel combination therapies/chemoprevention using dietary agents will be more beneficial against cancer. This promising combination should be examined in therapeutic trials of skin and possibly other cancers.

  3. Transcriptome signature of the adult mouse choroid plexus

    Directory of Open Access Journals (Sweden)

    Marques Fernanda

    2011-01-01

    Full Text Available Abstract Background Although the gene expression profile of several tissues in humans and in rodent animal models has been explored, analysis of the complete choroid plexus (CP transcriptome is still lacking. A better characterization of the CP transcriptome can provide key insights into its functions as one of the barriers that separate the brain from the periphery and in the production of cerebrospinal fluid. Methods This work extends further what is known about the mouse CP transcriptome through a microarray analysis of CP tissue from normal mice under physiological conditions. Results We found that the genes most highly expressed are those implicated in energy metabolism (oxidative phosphorylation, glycolysis/gluconeogenesis and in ribosomal function, which is in agreement with the secretory nature of the CP. On the other hand, genes encoding for immune mediators are among those with lower expression in basal conditions. In addition, we found genes known to be relevant during brain development, and not previously identified to be expressed in the CP, including those encoding for various axonal guidance and angiogenesis molecules and for growth factors. Some of these are known to influence the neural stem cell niche in the subventricular zone, highlighting the involvement of the CP as a likely modulator of neurogenesis. Interestingly, our observations confirm that the CP transcriptome is unique, displaying low homology with that of other tissues. Of note, we describe here that the closest similarity is with the transcriptome of the endothelial cells of the blood-brain barrier. Conclusions Based on the data presented here, it will now be possible to further explore the function of particular proteins of the CP secretome in health and in disease.

  4. Adult mouse cortical cell taxonomy revealed by single cell transcriptomics.

    Science.gov (United States)

    Tasic, Bosiljka; Menon, Vilas; Nguyen, Thuc Nghi; Kim, Tae Kyung; Jarsky, Tim; Yao, Zizhen; Levi, Boaz; Gray, Lucas T; Sorensen, Staci A; Dolbeare, Tim; Bertagnolli, Darren; Goldy, Jeff; Shapovalova, Nadiya; Parry, Sheana; Lee, Changkyu; Smith, Kimberly; Bernard, Amy; Madisen, Linda; Sunkin, Susan M; Hawrylycz, Michael; Koch, Christof; Zeng, Hongkui

    2016-02-01

    Nervous systems are composed of various cell types, but the extent of cell type diversity is poorly understood. We constructed a cellular taxonomy of one cortical region, primary visual cortex, in adult mice on the basis of single-cell RNA sequencing. We identified 49 transcriptomic cell types, including 23 GABAergic, 19 glutamatergic and 7 non-neuronal types. We also analyzed cell type-specific mRNA processing and characterized genetic access to these transcriptomic types by many transgenic Cre lines. Finally, we found that some of our transcriptomic cell types displayed specific and differential electrophysiological and axon projection properties, thereby confirming that the single-cell transcriptomic signatures can be associated with specific cellular properties.

  5. Differentiations of transplanted mouse spermatogonial stem cells in the adult mouse renal parenchyma in vivo

    Institute of Scientific and Technical Information of China (English)

    Da-peng WU; Da-lin HE; Xiang LI; Zhao-hui LIU

    2008-01-01

    Aim:Spermatogonial stem cells can initiate the process of cellular differentia-tion to generate mature spermatozoa, but whether it possess the characteristic of pluripotency and plasticity, similar to embryonic stem cells, has not been elucidated. This study was designed to evaluate the differentiation potential of spermatogonial stem cells into renal cells in vivo. Methods: Neonatal mouse spermatogonial stem cells were transplanted into mature male mice lacking en-dogenous spermatogenesis. The restoration of fertility in recipient males was observed. Spermatogonial stem cells were then injected into renal parenchyma of mature female mice to make a new extracellular environment for differentia-tion. Fluorescence in situ hybridization technology (FISH) was used to detect the expression of chromosome Y in recipient renal tissues. To determine the type of cells differentiated from spermatogonial stem cells, the expression of ricinus communis agglutinin, vimentin, CD45, and F4/80 proteins were examined in the renal tissues by immunohistochemistry. Results: The proliferation of seminiferous epithelial cells was distinctly observed in seminiferous tubules of transplanted testes, whereas no regeneration of spermatogenesis was observed in non-transplanted control testes. In transplanted female renal tissues, FISH showed a much stronger immuno-fluorescence signal of chromosome Y in the nucleolus of epithelial cells of the renal tubule and podocytes of the glomerulus. Conclusion: The spermatogonial stem cells were successfully purified from mouse testicles. This finding demonstrated that spermatogonial stem cells could not only restore damaged spermatogenesis, but were also capable of differentiat-ing into mature renal parenchyma cells in vivo.

  6. Thymoquinone inhibits phorbol ester-induced activation of NF-κB and expression of COX-2, and induces expression of cytoprotective enzymes in mouse skin in vivo.

    Science.gov (United States)

    Kundu, Joydeb Kumar; Liu, Lijia; Shin, Jun-Wan; Surh, Young-Joon

    2013-09-01

    Thymoquinone (TQ), the active ingredient of Nigella sativa, has been reported to possess anti-inflammatory and chemopreventive properties. The present study was aimed at elucidating the molecular mechanisms of anti-inflammatory and antioxidative activities of thymoquinone in mouse skin. Pretreatment of female HR-1 hairless mouse skin with TQ attenuated 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced expression of cyclooxygenase-2 (COX-2). TQ diminished nuclear translocation and the DNA binding of nuclear factor-kappaB (NF-κB) via the blockade of phosphorylation and subsequent degradation of IκBα in TPA-treated mouse skin. Pretreatment with TQ attenuated the phosphorylation of Akt, c-Jun-N-terminal kinase and p38 mitogen-activated protein kinase, but not that of extracellular signal-regulated kinase-1/2. Moreover, topical application of TQ induced the expression of heme oxygenase-1, NAD(P)H-quinoneoxidoreductase-1, glutathione-S-transferase and glutamate cysteine ligase in mouse skin. Taken together, the inhibitory effects of TQ on TPA-induced COX-2 expression and NF-κB activation, and its ability to induce the expression of cytoprotective proteins provide a mechanistic basis of anti-inflammatory and antioxidative effects of TQ in hairless mouse skin.

  7. DOSE-RESPONSE STUDIES OF SODIUM ARSENITE IN THE SKIN OF K6/ODC TRANSGENIC MOUSE

    Science.gov (United States)

    It has previously been observed that chronic exposure to inorganic arsenic and/or its metabolites increase(s) tumor frequency in the skin of K6/ODC transgenic mice. To identify potential biomarkers and modes of action for this skin tumorigenicity, gene expression profiles w...

  8. Otx2 Gene Deletion in Adult Mouse Retina Induces Rapid RPE Dystrophy and Slow Photoreceptor Degeneration

    OpenAIRE

    Francis Béby; Michael Housset; Nicolas Fossat; Coralie Le Greneur; Frédéric Flamant; Pierre Godement; Thomas Lamonerie

    2010-01-01

    Background : Many developmental genes are still active in specific tissues after development is completed. This is the case for the homeobox gene Otx2, an essential actor of forebrain and head development. In adult mouse, Otx2 is strongly expressed in the retina. Mutations of this gene in humans have been linked to severe ocular malformation and retinal diseases. It is, therefore, important to explore its post-developmental functions. In the mature retina, Otx2 is expressed in three cell type...

  9. Genetic influences on exercise-induced adult hippocampal neurogenesis across 12 divergent mouse strains

    OpenAIRE

    Clark, Peter J.; Kohman, Rachel A.; Miller, Daniel S.; Bhattacharya, Tushar K.; Brzezinska, Weronika J.; Rhodes, Justin S.

    2011-01-01

    New neurons are continuously born in the hippocampus of several mammalian species throughout adulthood. Adult neurogenesis represents a natural model for understanding how to grow and incorporate new nerve cells into pre-existing circuits in the brain. Finding molecules or biological pathways that increase neurogenesis has broad potential for regenerative medicine. One strategy is to identify mouse strains that display large versus small increases in neurogenesis in response to wheel running ...

  10. Exercise during pregnancy protects adult mouse offspring from diet-induced obesity

    OpenAIRE

    Wasinski, F.; Bacurau, R.F.P.; Estrela, G.R.; Klempin, F.; Arakaki, A.M.; Batista, R.O.; Mafra, F.F.P.; do Nascimento, L.F.R.; M.I. Hiyane; L.A. Velloso; N.O.S. Camara; Araujo, R C

    2015-01-01

    Background Physical exercise induces positive alterations in gene expression involved in the metabolism of obesity. Maternal exercise provokes adaptations soon after birth in the offspring. Here, we investigated whether adult mouse offspring of swim-trained mothers is protected against the development of the deleterious effects of high fat diet (HFD). Methods Our study comprises two parts. First, female C57BL/6 mice were divided into one sedentary and one swim-trained group (before and during...

  11. Isolation and Culture of Dental Epithelial Stem Cells from the Adult Mouse Incisor

    OpenAIRE

    Chavez, Miquella G.; Hu, Jimmy; SEIDEL, KERSTIN; Li, Chunying; Jheon, Andrew; Naveau, Adrien; Horst, Orapin; Klein, Ophir D.

    2014-01-01

    Understanding the cellular and molecular mechanisms that underlie tooth regeneration and renewal has become a topic of great interest1-4, and the mouse incisor provides a model for these processes. This remarkable organ grows continuously throughout the animal's life and generates all the necessary cell types from active pools of adult stem cells housed in the labial (toward the lip) and lingual (toward the tongue) cervical loop (CL) regions. Only the dental stem cells from the labial CL give...

  12. Distribution and ultrastructure of pigment cells in the skins of normal and albino adult turbot, Scophthalmus Maximus

    Institute of Scientific and Technical Information of China (English)

    GUO Huarong; HUANG Bing; QI Fei; ZHANG Shicui

    2007-01-01

    The distribution and ultrastructure of pigment cells in skins of normal and albino adult turbots were examined with transmission electron microscopy (TEM). Three types of pigment cells of melanophore, iridophore and xanthophore have been recognized in adult turbot skins. The skin color depends mainly on the amount and distribution of melanophore and iridophore, as xanthophore is quite rare. No pigment cells can be found in the epidermis of the skins. In the pigmented ocular skin of the turbot, melanophore and iridophore are usually co-localized in the dermis. This is quite different from the distribution in larvae skin. In albino and white blind skins of adult turbots, however, only iridophore monolayer still exists, while the melanophore monolayer disappears. This cytological evidence explains why the albino adult turbot, unlike its larvae, could never resume its body color no matter what environmental and nutritional conditions were provided. Endocytosis is quite active in the cellular membrane of the iridophore. This might be related to the formation of reflective platelet and stability of the iridophore.

  13. Retinoic acid receptor beta2 and neurite outgrowth in the adult mouse spinal cord in vitro.

    Science.gov (United States)

    Corcoran, Jonathan; So, Po-Lin; Barber, Robert D; Vincent, Karen J; Mazarakis, Nicholas D; Mitrophanous, Kyriacos A; Kingsman, Susan M; Maden, Malcolm

    2002-10-01

    Retinoic acid, acting through the nuclear retinoic acid receptor beta2 (RARbeta2), stimulates neurite outgrowth from peripheral nervous system tissue that has the capacity to regenerate neurites, namely, embryonic and adult dorsal root ganglia. Similarly, in central nervous system tissue that can regenerate, namely, embryonic mouse spinal cord, retinoic acid also stimulates neurite outgrowth and RARbeta2 is upregulated. By contrast, in the adult mouse spinal cord, which cannot regenerate, no such upregulation of RARbeta2 by retinoic acid is observed and no neurites are extended in vitro. To test our hypothesis that the upregulation of RARbeta2 is crucial to neurite regeneration, we have transduced adult mouse or rat spinal cord in vitro with a minimal equine infectious anaemia virus vector expressing RARbeta2. After transduction, prolific neurite outgrowth occurs. Outgrowth does not occur when the cord is transduced with a different isoform of RARbeta nor does it occur following treatment with nerve growth factor. These data demonstrate that RARbeta2 is involved in neurite outgrowth, at least in vitro, and that this gene may in the future be of some therapeutic use. PMID:12235288

  14. Neuro-muscular differentiation of adult porcine skin derived stem cell-like cells.

    Directory of Open Access Journals (Sweden)

    Dominik Lermen

    Full Text Available BACKGROUND: Due to the genetic relationship to humans, porcine stem cells are a very important model system to investigate cell differentiation, associated cell signaling pathways, and cell fate. Porcine skin derived stem cells have been isolated from mid-gestation porcine fetus recently. To our knowledge, stem cells from the skin of the adult porcine organism have not been isolated until now. Hence, to our knowledge, we here describe the isolation, expansion, characterization and differentiation of multipotent porcine skin derived stem cell-like cells (pSSCs from the adult porcine organism for the first time. METHODOLOGY/PRINCIPAL FINDINGS: pSSCs had a spindle shaped morphology similar to mesenchymal stem cells (MSCs. They could be maintained proliferatively active in vitro for more than 120 days and were able to form colonies from single cells. pSSCs expressed Sox2 and Oct3/4, both transcription factors essential to the pluripotent and self-renewing phenotypes of embryonic stem cells, which recently gained attention due to their function in inducing pluripotent stem cells. Furthermore, the expression of the progenitor marker nestin, the somatic stem cell markers Bcrp1/ABCG2, Bmi1, and Stat3 was detected by reverse transcriptase-polymerase chain reaction (RT-PCR in undifferentiated pSSCs. Flow cytometry revealed the expression of the MSC related proteins CD9, CD29, CD44 and CD105, but not CD90. After neuronal differentiation cells with a characteristic morphology of neuronal and smooth muscle-like cells were present in the cultures. Subsequent immunochemistry and flow cytometry revealed the down-regulation of nestin and the up-regulation of the neuron specific protein beta-III-tubulin and the astrocyte marker GFAP. Also, alpha-SMA expressing cells increased during differentiation suggesting the neuro-muscular differentiation of these skin derived cells. pSSCs could also be induced to differentiate into adipocyte-like cells when cultured under

  15. Deoxynivalenol induced mouse skin tumor initiation: Elucidation of molecular mechanisms in human HaCaT keratinocytes.

    Science.gov (United States)

    Mishra, Sakshi; Tewari, Prachi; Chaudhari, Bhushan P; Dwivedi, Premendra D; Pandey, Haushila P; Das, Mukul

    2016-11-01

    Among food contaminants, mycotoxins are toxic to both human and animal health. Our prior studies suggest that Deoxynivalenol (DON), a mycotoxin, behaves as a tumor promoter by inducing edema, hyperplasia, ODC activity and activation of MAPK's in mouse skin. In this study, topical application of DON, 336 and 672 nmol significantly enhanced ROS levels, DNA damage and apoptosis with concomitant downregulation of Ki-67, cyclin D, cyclin E, cyclin A and cyclin-dependent kinases (CDK4 and CDK2) thereby resulting in tumor initiation in mouse skin. Further, the elucidation of molecular mechanisms of tumor initiation by DON (0.42-3.37 nmol/ml) in HaCaT keratinocytes, revealed (i) enhanced ROS generation with cell cycle phase arrest in G0/G1 phase, (ii) increase in levels of 8-OxoG (6-24 hr) and γH2AX protein, (iii) significant enhancement in oxidative stress marker enzymes LPO, GSH, GR with concomitant decrease in antioxidant enzymes catalase, GPx, GST, SOD and mitochondrial membrane potential after DON (1.68 nmol) treatment, (iv) suppression of Nrf2 translocation to nucleus, enhanced phosphorylation with subsequent activation ERK1/2, p38 and JNK MAPK's following DON (1.68 nmol) treatment, (v) overexpression of c-jun, c-fos proteins, upregulation of Bax along with downregulation of Bcl-2 proteins, (vi) increase in cytochrome-c, caspase-9, caspase-3 and poly ADP ribose polymerase levels leads to apoptosis. Pretreatment of superoxide dismutase, mannitol and ethanol to HaCaT cells resulted in significant reduction in ROS levels and apoptosis indicating the role of superoxide and hydroxyl radicals in DON induced apoptosis as an early event and skin tumor initiation as a late event. PMID:27389473

  16. Deoxynivalenol induced mouse skin tumor initiation: Elucidation of molecular mechanisms in human HaCaT keratinocytes.

    Science.gov (United States)

    Mishra, Sakshi; Tewari, Prachi; Chaudhari, Bhushan P; Dwivedi, Premendra D; Pandey, Haushila P; Das, Mukul

    2016-11-01

    Among food contaminants, mycotoxins are toxic to both human and animal health. Our prior studies suggest that Deoxynivalenol (DON), a mycotoxin, behaves as a tumor promoter by inducing edema, hyperplasia, ODC activity and activation of MAPK's in mouse skin. In this study, topical application of DON, 336 and 672 nmol significantly enhanced ROS levels, DNA damage and apoptosis with concomitant downregulation of Ki-67, cyclin D, cyclin E, cyclin A and cyclin-dependent kinases (CDK4 and CDK2) thereby resulting in tumor initiation in mouse skin. Further, the elucidation of molecular mechanisms of tumor initiation by DON (0.42-3.37 nmol/ml) in HaCaT keratinocytes, revealed (i) enhanced ROS generation with cell cycle phase arrest in G0/G1 phase, (ii) increase in levels of 8-OxoG (6-24 hr) and γH2AX protein, (iii) significant enhancement in oxidative stress marker enzymes LPO, GSH, GR with concomitant decrease in antioxidant enzymes catalase, GPx, GST, SOD and mitochondrial membrane potential after DON (1.68 nmol) treatment, (iv) suppression of Nrf2 translocation to nucleus, enhanced phosphorylation with subsequent activation ERK1/2, p38 and JNK MAPK's following DON (1.68 nmol) treatment, (v) overexpression of c-jun, c-fos proteins, upregulation of Bax along with downregulation of Bcl-2 proteins, (vi) increase in cytochrome-c, caspase-9, caspase-3 and poly ADP ribose polymerase levels leads to apoptosis. Pretreatment of superoxide dismutase, mannitol and ethanol to HaCaT cells resulted in significant reduction in ROS levels and apoptosis indicating the role of superoxide and hydroxyl radicals in DON induced apoptosis as an early event and skin tumor initiation as a late event.

  17. Brain transcriptional stability upon prion protein-encoding gene invalidation in zygotic or adult mouse

    Directory of Open Access Journals (Sweden)

    Béringue Vincent

    2010-07-01

    Full Text Available Abstract Background The physiological function of the prion protein remains largely elusive while its key role in prion infection has been expansively documented. To potentially assess this conundrum, we performed a comparative transcriptomic analysis of the brain of wild-type mice with that of transgenic mice invalidated at this locus either at the zygotic or at the adult stages. Results Only subtle transcriptomic differences resulting from the Prnp knockout could be evidenced, beside Prnp itself, in the analyzed adult brains following microarray analysis of 24 109 mouse genes and QPCR assessment of some of the putatively marginally modulated loci. When performed at the adult stage, neuronal Prnp disruption appeared to sequentially induce a response to an oxidative stress and a remodeling of the nervous system. However, these events involved only a limited number of genes, expression levels of which were only slightly modified and not always confirmed by RT-qPCR. If not, the qPCR obtained data suggested even less pronounced differences. Conclusions These results suggest that the physiological function of PrP is redundant at the adult stage or important for only a small subset of the brain cell population under classical breeding conditions. Following its early reported embryonic developmental regulation, this lack of response could also imply that PrP has a more detrimental role during mouse embryogenesis and that potential transient compensatory mechanisms have to be searched for at the time this locus becomes transcriptionally activated.

  18. Effects of Intense Pulsed Light on Tissue Vascularity and Wound Healing: A Study with Mouse Island Skin Flap Model

    Directory of Open Access Journals (Sweden)

    Trinh Cao Minh

    2015-01-01

    Full Text Available Intense pulsed light (IPL has been used extensively in aesthetic and cosmetic dermatology. To test whether IPL could change the tissue vascularity and improve wound healing, mice were separated into 4 groups. Mice in Group I were not treated with IPL, whereas, dorsal skins of mice in Groups II, III, and IV were treated with 35 J/cm2, 25 J/cm2, and 15 J/cm2 IPL, respectively. After 2 weeks, dorsal island skin flaps were raised, based on the left deep circumflex iliac vessels as pedicles; then, survival rate was assessed. Flaps in Group IV (treated with lowest dose of IPL have a survival rate significantly higher than other groups. Counting blood vessels did not demonstrate any significant differences; however, vessel dilation was found in this group. The results show that IPL at the therapeutic doses which are usually applied to humans is harmful to mouse dorsal skin and did not enhance wound healing, whereas, IPL at much lower dose could improve wound healing. The possible mechanism is the dilation of tissue vasculature thanks to the electromagnetic character of IPL. Another mechanism could be the heat-shock protein production.

  19. Sarcophine-Diol, a Skin Cancer Chemopreventive Agent, Inhibits Proliferation and Stimulates Apoptosis in Mouse Melanoma B16F10 Cell Line

    OpenAIRE

    Hesham Fahmy; Ahmed, Safwat A.; Szymanski, Pawel T.; Bhimanna Kuppast; Sherief Khalifa

    2011-01-01

    Sarcodiol (SD) is a semi-synthetic derivative of sarcophine, a marine natural product. In our previous work, we reported the significant chemopreventive effects of SD against non-melanoma skin cancer both in vitro and in vivo mouse models. In this investigation, we extended this work to study the effect of sarcodiol on melanoma development, the more deadly form of skin cancer, using the mouse melanoma B16F10 cell line. In this study we report that SD inhibits the de novo DNA synthesis and enh...

  20. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus.

    Science.gov (United States)

    van Praag, H; Kempermann, G; Gage, F H

    1999-03-01

    Exposure to an enriched environment increases neurogenesis in the dentate gyrus of adult rodents. Environmental enrichment, however, typically consists of many components, such as expanded learning opportunities, increased social interaction, more physical activity and larger housing. We attempted to separate components by assigning adult mice to various conditions: water-maze learning (learner), swim-time-yoked control (swimmer), voluntary wheel running (runner), and enriched (enriched) and standard housing (control) groups. Neither maze training nor yoked swimming had any effect on bromodeoxyuridine (BrdU)-positive cell number. However, running doubled the number of surviving newborn cells, in amounts similar to enrichment conditions. Our findings demonstrate that voluntary exercise is sufficient for enhanced neurogenesis in the adult mouse dentate gyrus.

  1. Cranial irradiation induces bone marrow-derived microglia in adult mouse brain tissue.

    Science.gov (United States)

    Okonogi, Noriyuki; Nakamura, Kazuhiro; Suzuki, Yoshiyuki; Suto, Nana; Suzue, Kazutomo; Kaminuma, Takuya; Nakano, Takashi; Hirai, Hirokazu

    2014-07-01

    Postnatal hematopoietic progenitor cells do not contribute to microglial homeostasis in adult mice under normal conditions. However, previous studies using whole-body irradiation and bone marrow (BM) transplantation models have shown that adult BM cells migrate into the brain tissue and differentiate into microglia (BM-derived microglia; BMDM). Here, we investigated whether cranial irradiation alone was sufficient to induce the generation of BMDM in the adult mouse brain. Transgenic mice that express green fluorescent protein (GFP) under the control of a murine stem cell virus (MSCV) promoter (MSCV-GFP mice) were used. MSCV-GFP mice express GFP in BM cells but not in the resident microglia in the brain. Therefore, these mice allowed us to detect BM-derived cells in the brain without BM reconstitution. MSCV-GFP mice, aged 8-12 weeks, received 13.0 Gy irradiation only to the cranium, and BM-derived cells in the brain were quantified at 3 and 8 weeks after irradiation. No BM-derived cells were detected in control non-irradiated MSCV-GFP mouse brains, but numerous GFP-labeled BM-derived cells were present in the brain stem, basal ganglia and cerebral cortex of the irradiated MSCV-GFP mice. These BM-derived cells were positive for Iba1, a marker for microglia, indicating that GFP-positive BM-derived cells were microglial in nature. The population of BMDM was significantly greater at 8 weeks post-irradiation than at 3 weeks post-irradiation in all brain regions examined. Our results clearly show that cranial irradiation alone is sufficient to induce the generation of BMDM in the adult mouse.

  2. Exploration and visualization of gene expression with neuroanatomy in the adult mouse brain

    Directory of Open Access Journals (Sweden)

    Pathak Sayan

    2008-03-01

    Full Text Available Abstract Background Spatially mapped large scale gene expression databases enable quantitative comparison of data measurements across genes, anatomy, and phenotype. In most ongoing efforts to study gene expression in the mammalian brain, significant resources are applied to the mapping and visualization of data. This paper describes the implementation and utility of Brain Explorer, a 3D visualization tool for studying in situ hybridization-based (ISH expression patterns in the Allen Brain Atlas, a genome-wide survey of 21,000 expression patterns in the C57BL6J adult mouse brain. Results Brain Explorer enables users to visualize gene expression data from the C57Bl/6J mouse brain in 3D at a resolution of 100 μm3, allowing co-display of several experiments as well as 179 reference neuro-anatomical structures. Brain Explorer also allows viewing of the original ISH images referenced from any point in a 3D data set. Anatomic and spatial homology searches can be performed from the application to find data sets with expression in specific structures and with similar expression patterns. This latter feature allows for anatomy independent queries and genome wide expression correlation studies. Conclusion These tools offer convenient access to detailed expression information in the adult mouse brain and the ability to perform data mining and visualization of gene expression and neuroanatomy in an integrated manner.

  3. Sertoli cells maintain Leydig cell number and peritubular myoid cell activity in the adult mouse testis.

    Directory of Open Access Journals (Sweden)

    Diane Rebourcet

    Full Text Available The Sertoli cells are critical regulators of testis differentiation and development. In the adult, however, their known function is restricted largely to maintenance of spermatogenesis. To determine whether the Sertoli cells regulate other aspects of adult testis biology we have used a novel transgenic mouse model in which Amh-Cre induces expression of the receptor for Diphtheria toxin (iDTR specifically within Sertoli cells. This causes controlled, cell-specific and acute ablation of the Sertoli cell population in the adult animal following Diphtheria toxin injection. Results show that Sertoli cell ablation leads to rapid loss of all germ cell populations. In addition, adult Leydig cell numbers decline by 75% with the remaining cells concentrated around the rete and in the sub-capsular region. In the absence of Sertoli cells, peritubular myoid cell activity is reduced but the cells retain an ability to exclude immune cells from the seminiferous tubules. These data demonstrate that, in addition to support of spermatogenesis, Sertoli cells are required in the adult testis both for retention of the normal adult Leydig cell population and for support of normal peritubular myoid cell function. This has implications for our understanding of male reproductive disorders and wider androgen-related conditions affecting male health.

  4. Ablation of mouse adult neurogenesis alters olfactory bulb structure and olfactory fear conditioning

    Directory of Open Access Journals (Sweden)

    Matthew Valley

    2009-11-01

    Full Text Available Adult neurogenesis replenishes olfactory bulb (OB interneurons throughout the life of most mammals, yet during this constant fl ux it remains unclear how the OB maintains a constant structure and function. In the mouse OB, we investigated the dynamics of turnover and its impact on olfactory function by ablating adult neurogenesis with an x-ray lesion to the subventricular zone (SVZ. Regardless of the magnitude of the lesion to the SVZ, we found no change in the survival of young adult born granule cells (GCs born after the lesion, and a gradual decrease in the population of GCs born before the lesion. After a lesion producing a 96% reduction of incoming adult born GCs to the OB, we found a diminished behavioral fear response to conditioned odor cues but not to audio cues. Interestingly, despite this behavioral defi cit and gradual anatomical changes, we found no electrophysiological changes in the GC population assayed in vivo through dendro-dendritic synaptic plasticity and odor-evoked local fi eld potential oscillations. These data indicate that turnover in the granule cell layer is generally decoupled from the rate of adult neurogenesis, and that OB adult neurogenesis plays a role in a wide behavioral system extending beyond the OB.

  5. Early changes produced in mouse skin by the application of three middle distillates.

    Science.gov (United States)

    Grasso, P; Sharratt, M; Ingram, A J

    1988-01-01

    It has been reported by the American Petroleum Institute (API) that dermal applications of certain middle distillates of mineral oils can result in high incidences of skin tumours in mice. This was unexpected as the polycyclic aromatic hydrocarbon (PAH) levels in these were below detection limits. To examine the possible role of tissue injury in the induction of tumours, the skin reactions produced by thrice weekly applications of three middle distillates similar to those tested by the API were examined grossly and histopathologically at intervals up to 6 weeks. Various reference materials and oils were used as controls. Preliminary histological examination showed that severe skin damage was present from week 1 onwards in mice treated with the three middle distillates, two of them producing epidermal loss and ulceration. Marked epidermal hyperplasia was produced by all three middle distillates. These findings support the view that regenerative epidermal hyperplasia due to repeated severe skin damage may have exerted a powerful promotional effect in the production of the skin tumours by middle distillates in the API study. PMID:3180034

  6. The Ly-6A (Sca-1) GFP transgene is expressed in all adult mouse hematopoietic stem cells

    NARCIS (Netherlands)

    X. Ma (Xiaoqian); C.I. Robin; K. Ottersbach (Katrin); E.A. Dzierzak (Elaine)

    2002-01-01

    textabstractThe Sca-1 cell surface glycoprotein is used routinely as a marker of adult hematopoietic stem cells (HSCs), allowing a >100-fold enrichment of these rare cells from the bone marrow of the adult mouse. The Sca-1 protein is encoded by the Ly-6A/E gene, a small 4-exon gene

  7. Ultrastructural analysis of adult mouse neocortex comparing aldehyde perfusion with cryo fixation.

    Science.gov (United States)

    Korogod, Natalya; Petersen, Carl C H; Knott, Graham W

    2015-01-01

    Analysis of brain ultrastructure using electron microscopy typically relies on chemical fixation. However, this is known to cause significant tissue distortion including a reduction in the extracellular space. Cryo fixation is thought to give a truer representation of biological structures, and here we use rapid, high-pressure freezing on adult mouse neocortex to quantify the extent to which these two fixation methods differ in terms of their preservation of the different cellular compartments, and the arrangement of membranes at the synapse and around blood vessels. As well as preserving a physiological extracellular space, cryo fixation reveals larger numbers of docked synaptic vesicles, a smaller glial volume, and a less intimate glial coverage of synapses and blood vessels compared to chemical fixation. The ultrastructure of mouse neocortex therefore differs significantly comparing cryo and chemical fixation conditions. PMID:26259873

  8. Liver repopulation and correction of metabolic liver disease by transplanted adult mouse pancreatic cells.

    Science.gov (United States)

    Wang, X; Al-Dhalimy, M; Lagasse, E; Finegold, M; Grompe, M

    2001-02-01

    The emergence of cells with hepatocellular properties in the adult pancreas has been described in several experimental models. To determine whether adult pancreas contains cells that can give rise to therapeutically useful and biochemically normal hepatocytes, we transplanted suspensions of wild-type mouse pancreatic cells into syngeneic recipients deficient in fumarylacetoacetate hydrolase and manifesting tyrosinemia. Four of 34 (12%) mutant mice analyzed were fully rescued by donor-derived cells and had normal liver function. Ten additional mice (29%) showed histological evidence of donor-derived hepatocytes in the liver. Previous work has suggested that pancreatic liver precursors reside within or close to pancreatic ducts. We therefore performed additional transplantations using either primary cell suspensions enriched for ducts or cultured ducts. Forty-four mutant mice were transplanted with cells enriched for pancreatic duct cells, but only three of the 34 (9%) recipients analyzed displayed donor-derived hepatocytes. In addition, 28 of the fumarylacetoacetate hydrolase-deficient mice were transplanted with cultured pancreatic duct cells, but no donor-derived hepatocytes were observed. Our results demonstrate for the first time that adult mouse pancreas contains hepatocyte progenitor cells capable of significant therapeutic liver reconstitution. However, contrary to previous reports, we were unable to detect these cells within the duct compartment. PMID:11159194

  9. Effects of low-level laser therapy, electroacupuncture, and radiofrequency on the pigmentation and skin tone of adult women.

    Science.gov (United States)

    Kim, Hee-Kyoung; Min, Kyoung-Ok; Choi, Jung-Hyun; Kim, Soon-Hee

    2016-05-01

    [Purpose] In this study, the effects of low-level laser therapy (LLLT), electroacupuncture (EA), and radiofrequency (RF), which are used in physical therapy, on the pigmentation and skin tone of adult women's faces were investigated to provide basic data for skin interventions. [Subjects and Methods] Thirty adult females were assigned to either an LLLT group (n=10), an EA group (n=10), or an RF group (n=10). The intervention was performed in two 15-minute sessions per week for six weeks. Subjects' skin tone and pigmentation were observed before and after the intervention. [Results] The EA group showed significant reductions in pigmentation in the left and right eye rims, as well as in the left cheek. The RF group showed significant post-intervention reductions in pigmentation under the left eye, as well as in the left and right eye rims and the left cheek. The LLLT group showed significant increases in skin tone in the forehead and both eye rims. The RF group showed significant increases in skin tone under both eyes. [Conclusion] The application of LLLT, EA, and RF had positive effects on pigmentation and skin tone of adult women's faces. PMID:27313340

  10. In Vivo SILAC-Based Proteomics Reveals Phosphoproteome Changes during Mouse Skin Carcinogenesis

    DEFF Research Database (Denmark)

    Zanivan, Sara; Meves, Alexander; Behrendt, Kristina;

    2013-01-01

    SILAC technology in combination with high-resolution mass spectrometry (MS) can be successfully used to measure phosphoproteomes in vivo. Here, Zanivan, Mann, and colleagues have applied SILAC-based MS to investigate phosphoproteomic changes during skin carcinogenesis, using the DMBA/TPA two-stag...

  11. Optical Monitoring of Living Nerve Terminal Labeling in Hair Follicle Lanceolate Endings of the Ex Vivo Mouse Ear Skin.

    Science.gov (United States)

    Bewick, Guy S; Banks, Robert W

    2016-01-01

    A novel dissection and recording technique is described for optical monitoring staining and de-staining of lanceolate terminals surrounding hair follicles in the skin of the mouse pinna. The preparation is simple and relatively fast, reliably yielding extensive regions of multiple labeled units of living nerve terminals to study uptake and release of styryl pyridinium dyes extensively used in studies of vesicle recycling. Subdividing the preparations before labeling allows test vs. control comparisons in the same ear from a single individual. Helpful tips are given for improving the quality of the preparation, the labeling and the imaging parameters. This new system is suitable for assaying pharmacologically and mechanically-induced uptake and release of these vital dyes in lanceolate terminals in both wild-type and genetically modified animals. Examples of modulatory influences on labeling intensity are given. PMID:27077818

  12. Cathepsin B-dependent motor neuron death after nerve injury in the adult mouse

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Li; Wu, Zhou; Baba, Masashi [Department of Aging Science and Pharmacology, Faculty of Dental Sciences, Kyushu University, Maidashi 3-1-1, Fukuoka 812-8582 (Japan); Peters, Christoph [Institute fuer Molekulare Medizin und Zellforshung, Albert-Ludwings-Universitaet Freiburg, D-79104 Freiburg (Germany); Uchiyama, Yasuo [Department of Cell Biology and Neuroscience, Juntendo University Graduate School of Medicine, Tokyo (Japan); Nakanishi, Hiroshi, E-mail: nakan@dent.kyushu-u.ac.jp [Department of Aging Science and Pharmacology, Faculty of Dental Sciences, Kyushu University, Maidashi 3-1-1, Fukuoka 812-8582 (Japan)

    2010-08-27

    Research highlights: {yields} Cathepsin B (CB), a lysosomal cysteine protease, is expressed in neuron and glia. {yields} CB increased in hypogrossal nucleus neurons after nerve injury in adult mice. {yields} CB-deficiency significantly increased the mean survival ratio of injured neurons. {yields} Thus, CB plays a critical role in axotomy-induced neuronal death in adult mice. -- Abstract: There are significant differences in the rate of neuronal death after peripheral nerve injury between species. The rate of neuronal death of motor neurons after nerve injury in the adult rats is very low, whereas that in adult mice is relatively high. However, the understanding of the mechanism underlying axotomy-induced motor neuron death in adult mice is limited. Cathepsin B (CB), a typical cysteine lysosomal protease, has been implicated in three major morphologically distinct pathways of cell death; apoptosis, necrosis and autophagic cell death. The possible involvement of CB in the neuronal death of hypogrossal nucleus (HGN) neurons after nerve injury in adult mice was thus examined. Quantitative analyses showed the mean survival ratio of HGN neurons in CB-deficient (CB-/-) adult mice after nerve injury was significantly greater than that in the wild-type mice. At the same time, proliferation of microglia in the injured side of the HGN of CB-/- adult mice was markedly reduced compared with that in the wild-type mice. On the injured side of the HGN in the wild-type adult mice, both pro- and mature forms of CB markedly increased in accordance with the increase in the membrane-bound form of LC3 (LC3-II), a marker protein of autophagy. Furthermore, the increase in CB preceded an increase in the expression of Noxa, a major executor for axotomy-induced motor neuron death in the adult mouse. Conversely, expression of neither Noxa or LC3-II was observed in the HGN of adult CB-/- mice after nerve injury. These observations strongly suggest that CB plays a critical role in axotomy

  13. Relative biological effectiveness of carbon ions for tumor control, acute skin damage and late radiation-induced fibrosis in a mouse model

    DEFF Research Database (Denmark)

    Sørensen, Brita Singers; Horsman, Michael Robert; Alsner, Jan;

    2015-01-01

    Background. The aim of the present study was to compare the biological effectiveness of carbon ions relative to x-rays between tumor control, acute skin reaction and late RIF of CDF1 mice. Material and methods. CDF1 mice with a C3H mouse mammary carcinoma implanted subcutaneously on the foot of t...

  14. Effects of low-level laser therapy, electroacupuncture, and radiofrequency on the pigmentation and skin tone of adult women

    OpenAIRE

    Kim, Hee-Kyoung; Min, Kyoung-Ok; Choi, Jung-Hyun; Kim, Soon-Hee

    2016-01-01

    [Purpose] In this study, the effects of low-level laser therapy (LLLT), electroacupuncture (EA), and radiofrequency (RF), which are used in physical therapy, on the pigmentation and skin tone of adult women’s faces were investigated to provide basic data for skin interventions. [Subjects and Methods] Thirty adult females were assigned to either an LLLT group (n=10), an EA group (n=10), or an RF group (n=10). The intervention was performed in two 15-minute sessions per week for six weeks. Subj...

  15. Hair Follicle Morphogenesis in the Treatment of Mouse Full-Thickness Skin Defects Using Composite Human Acellular Amniotic Membrane and Adipose Derived Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Wu Minjuan

    2016-01-01

    Full Text Available Early repair of skin injury and maximal restoration of the function and appearance have become important targets of clinical treatment. In the present study, we observed the healing process of skin defects in nude mice and structural characteristics of the new skin after transplantation of isolated and cultured adipose derived mesenchymal stem cells (ADMSCs onto the human acellular amniotic membrane (AAM. The result showed that ADMSCs were closely attached to the surface of AAM and grew well 24 h after seeding. Comparison of the wound healing rate at days 7, 14, and 28 after transplantation showed that ADMSCs seeded on AAM facilitated the healing of full-thickness skin wounds more effectively as compared with either hAM or AAM alone, indicating that ADMSCs participated in skin regeneration. More importantly, we noticed a phenomenon of hair follicle development during the process of skin repair. Composite ADMSCs and AAM not only promoted the healing of the mouse full-thickness defects but also facilitated generation of the appendages of the affected skin, thus promoting restoration of the skin function. Our results provide a new possible therapy idea for the treatment of skin wounds with respect to both anatomical regeneration and functional restoration.

  16. Genetically engineered mouse models for skin research: taking the next step

    OpenAIRE

    Chen, Jiang; Roop, Dennis R.

    2008-01-01

    Genetically engineered mouse models are invaluable to investigators in nearly all areas of biomedical research. The use of genetically engineered mice has allowed researchers to explore fundamental functions of genes in a mammal that shares substantial similarities with human physiology and pathology. Genetically engineered mice are often used as animal models of human diseases that are vital tools in investigating disease development and in developing and testing novel therapies. Gene target...

  17. Inhibition of DMBA/croton oil-induced two-stage mouse skin carcinogenesis by diphenylmethyl selenocyanate.

    Science.gov (United States)

    Das, R K; Ghosh, S; Sengupta, A; Das, S; Bhattacharya, S

    2004-10-01

    Selenium, an essential micronutrient, is associated with antioxidant functions, physiological defence mechanisms against different diseases including several types of cancers. Search for new selenium compounds with more chemopreventive activities and lesser toxicities are in progress. In the present study, the antioxidative roles of a synthetic organoselenium compound, diphenylmethyl selenocyanate, were evaluated against 7,12-dimethylbenz(a)anthracene (DMBA)/croton oil-induced two-stage mouse skin carcinogenesis model. The compound was administered orally in carcinogen-induced mice in two different non-toxic doses: 2 mg/kg body weight and 3 mg/kg body weight. Significant inhibition in the incidence of papilloma formation (58-80%) as well as in the cumulative number of papilloma per papilloma-bearing mouse were observed in the treated groups as compared with the carcinogen control group. The compound was also found to significantly upregulate different phase II detoxifying enzymes in liver cytosol such as glutathione-S-transferase (Pliver microsomes was significantly inhibited (P<0.05) in a dose-dependent manner by diphenylmethyl selenocyanate. Thus the compound exerts its chemopreventive activity by reducing papilloma formation during chemically induced carcinogenesis, which in turn, may be through modulating the level of lipid peroxidation and phase II detoxifying enzyme system at the doses evaluated. PMID:15452454

  18. Disruption of protein kinase Ceta results in impairment of wound healing and enhancement of tumor formation in mouse skin carcinogenesis.

    Science.gov (United States)

    Chida, Kazuhiro; Hara, Takeshi; Hirai, Takaaki; Konishi, Chieko; Nakamura, Kenji; Nakao, Kazuki; Aiba, Atsu; Katsuki, Motoya; Kuroki, Toshio

    2003-05-15

    We have generated a mouse strain lacking protein kinase C (PKC) eta to evaluate its significance in epithelial organization and tumor formation. The PKCeta-deficient mice exhibited increased susceptibility to tumor formation in two-stage skin carcinogenesis by single application of 7,12-dimethylbenz(a)anthracene (DMBA) for tumor initiation and repeated applications of 12-O-tetradecanoylphorbol-13-acetate (TPA) for tumor promotion. The tumor formation was not enhanced by DMBA or TPA treatment alone, suggesting that PKCeta suppresses tumor promotion. Epidermal hyperplasia induced by topical TPA treatment was prolonged in the mutant mice. The enhanced tumor formation may be closely associated with the prolonged hyperplasia induced by topical TPA treatment. In the mutant mice, after inflicting injury by punch biopsy, wound healing on the dorsal skin, particularly reepithelialization, was significantly delayed and impaired in structure. Impairment of epithelial regeneration in wound healing indicates a possibility that PKCeta plays a role in maintenance of epithelial architecture. Homeostasis in epithelial tissues mediated by PKCeta is important for tumor formation in vivo. We propose that PKCeta is involved in tumor formation modulated by regulation of proliferation and remodeling of epithelial cells in vivo. PMID:12750259

  19. Intravital two-photon microscopy of host-pathogen interactions in a mouse model of Staphylococcus aureus skin abscess formation.

    Science.gov (United States)

    Liese, Jan; Rooijakkers, Suzan H M; van Strijp, Jos A G; Novick, Richard P; Dustin, Michael L

    2013-06-01

    Staphylococcus (S.) aureus is a frequent cause of severe skin infections. The ability to control the infection is largely dependent on the rapid recruitment of neutrophils (PMN). To gain more insight into the dynamics of PMN migration and host-pathogen interactions in vivo, we used intravital two-photon (2-P) microscopy to visualize S. aureus skin infections in the mouse. Reporter S. aureus strains expressing fluorescent proteins were developed, which allowed for detection of the bacteria in vivo. By employing LysM-EGFP mice to visualize PMN, we observed the rapid appearance of PMN in the extravascular space of the dermis and their directed movement towards the focus of infection, which led to the delineation of an abscess within 1 day. Moreover, tracking of transferred labelled bone-marrow neutrophils showed that PMN localization to the site of infection is dependent on the presence of G-protein-coupled receptors on the PMN, whereas Interleukin-1 receptor was required on host cells other than PMN. Furthermore, the S. aureus complement inhibitor Ecb could block PMN accumulation at thesite of infection. Our results establish that 2-P microscopy is a powerful tool to investigate the orchestration of the immune cells, S. aureus location and gene expression in vivo on a single cell level.

  20. Transcription-coupled repair: Impact on UV-induced mutagenesis in cultured rodent cells and mouse skin tumors

    International Nuclear Information System (INIS)

    UV-induced cyclobutane pyrimidine dimers (CPDs) are removed with accelerated speed from the transcribed strand of expressed genes in cultured mammalian cells by a process called transcription-coupled repair (TCR). It has been previously shown that this phenomenon has consequences for the molecular nature of the mutations induced by UV-light. Here, we review these data and show that TCR has not only a clear impact on UV-induced mutations in cultured mammalian cells but also on genes involved in tumor formation in the skin of UV-exposed mice. Mutations observed in the p53 gene in UV-induced squamous cell carcinoma are predominantly found at sites of dipyrimidines in the non-transcribed strand. In contrast, in UVC-irradiated Csb -/- Chinese hamster cells and in UVB-induced tumors in the Csb -/- mouse, almost all mutations are at positions of dipyrimidine sites in the transcribed strand of the mutated gene. Csb -/- mice appear to be susceptible to UVB-induced skin cancer in contrast to the human CSB patients. We speculate that the UVB-induced cancer susceptibility of Csb -/- mice is related to the absence of TCR as well as to a lack of a compensating global genome repair system for CPDs in mice

  1. The effect of ginkgo biloba extract on radiosensitivity of mouse skin and jejunal crypt

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Kyung Hwan; Ha, Sung Whan [Seoul National Univ. Medical College, Seoul (Korea, Republic of)

    1998-06-01

    Ginkgo biloba extract(GBE) is known to increase the peripheral blood circulation. This study was designed to evaluate the effect of GBE on the acute normal tissue radiation reaction. C3H mice were divided into two groups, radiation alone and two doses GBE plus radiation, for both acute skin reaction and jejunal crypt assay. GBE was given i.p. one hour before irradiation with priming dose given one day earlier. Thirty to Fifty Gy for acute skin reaction and 11 to 14 Gy for jejunal crypt were irradiated to right hind leg and whole body, respectively. Radiation doses(RD{sub 50}) for peak skin score of 2.0 were 44.2Gy(40.6-48.2Gy) for radiation alone and 44.4Gy(41.6-47.4Gy) for two doses GBE plus radiation, showing no effect of GBE on acute radiation skin damage. The numbers of regenerating jejunal crypts per circumference were also almost the same for each radiation dose level(p=0.57-0.94), and the mean lethal doses(D{sub o}) were 1.80Gy(1.57-2.09Gy) for radiation alone and 1.88Gy(1.65-2.18Gy) for two doses GBE plus radiation, indicating no effect of GBE on jejunal crypt cell survival after radiation. GBE doesn't increase acute normal tissue radiation reaction in this model system. As GBE was verified to enhance radiation effect on tumor, high therapeutic gain is expected when GBE is combined with radiation therapy.

  2. Nitisinone improves eye and skin pigmentation defects in a mouse model of oculocutaneous albinism

    OpenAIRE

    Onojafe, Ighovie F.; Adams, David R; Simeonov, Dimitre R.; Zhang, Jun; Chan, Chi-Chao; Bernardini, Isa M.; Sergeev, Yuri V.; Dolinska, Monika B.; Alur, Ramakrishna P.; Brilliant, Murray H.; William A Gahl; Brooks, Brian P.

    2011-01-01

    Mutation of the tyrosinase gene (TYR) causes oculocutaneous albinism, type 1 (OCA1), a condition characterized by reduced skin and eye melanin pigmentation and by vision loss. The retinal pigment epithelium influences postnatal visual development. Therefore, increasing ocular pigmentation in patients with OCA1 might enhance visual function. There are 2 forms of OCA1, OCA-1A and OCA-1B. Individuals with the former lack functional tyrosinase and therefore lack melanin, while individuals with th...

  3. A polygenic mouse model of psoriasiform skin disease in CD18-deficient mice.

    OpenAIRE

    Bullard, D C; Scharffetter-Kochanek, K; McArthur, M J; Chosay, J. G.; McBride, M E; Montgomery, C A; Beaudet, A L

    1996-01-01

    Previously, a hypomorphic mutation in CD18 was generated by gene targeting, with homozygous mice displaying increased circulating neutrophil counts, defects in the response to chemically induced peritonitis, and delays in transplantation rejection. When this mutation was backcrossed onto the PL/J inbred strain, virtually all homozygous mice developed a chronic inflammatory skin disease with a mean age of onset of 11 weeks after birth. The disease was characterized by erythema, hair loss, and ...

  4. The effect of ginkgo biloba extract on radiosensitivity of mouse skin and jejunal crypt

    International Nuclear Information System (INIS)

    Ginkgo biloba extract(GBE) is known to increase the peripheral blood circulation. This study was designed to evaluate the effect of GBE on the acute normal tissue radiation reaction. C3H mice were divided into two groups, radiation alone and two doses GBE plus radiation, for both acute skin reaction and jejunal crypt assay. GBE was given i.p. one hour before irradiation with priming dose given one day earlier. Thirty to Fifty Gy for acute skin reaction and 11 to 14 Gy for jejunal crypt were irradiated to right hind leg and whole body, respectively. Radiation doses(RD50) for peak skin score of 2.0 were 44.2Gy(40.6-48.2Gy) for radiation alone and 44.4Gy(41.6-47.4Gy) for two doses GBE plus radiation, showing no effect of GBE on acute radiation skin damage. The numbers of regenerating jejunal crypts per circumference were also almost the same for each radiation dose level(p=0.57-0.94), and the mean lethal doses(Do) were 1.80Gy(1.57-2.09Gy) for radiation alone and 1.88Gy(1.65-2.18Gy) for two doses GBE plus radiation, indicating no effect of GBE on jejunal crypt cell survival after radiation. GBE doesn't increase acute normal tissue radiation reaction in this model system. As GBE was verified to enhance radiation effect on tumor, high therapeutic gain is expected when GBE is combined with radiation therapy

  5. Otx2 gene deletion in adult mouse retina induces rapid RPE dystrophy and slow photoreceptor degeneration.

    Directory of Open Access Journals (Sweden)

    Francis Béby

    Full Text Available BACKGROUND: Many developmental genes are still active in specific tissues after development is completed. This is the case for the homeobox gene Otx2, an essential actor of forebrain and head development. In adult mouse, Otx2 is strongly expressed in the retina. Mutations of this gene in humans have been linked to severe ocular malformation and retinal diseases. It is, therefore, important to explore its post-developmental functions. In the mature retina, Otx2 is expressed in three cell types: bipolar and photoreceptor cells that belong to the neural retina and retinal pigment epithelium (RPE, a neighbour structure that forms a tightly interdependent functional unit together with photoreceptor cells. METHODOLOGY/PRINCIPAL FINDINGS: Conditional self-knockout was used to address the late functions of Otx2 gene in adult mice. This strategy is based on the combination of a knock-in CreERT2 allele and a floxed allele at the Otx2 locus. Time-controlled injection of tamoxifen activates the recombinase only in Otx2 expressing cells, resulting in selective ablation of the gene in its entire domain of expression. In the adult retina, loss of Otx2 protein causes slow degeneration of photoreceptor cells. By contrast, dramatic changes of RPE activity rapidly occur, which may represent a primary cause of photoreceptor disease. CONCLUSIONS: Our novel mouse model uncovers new Otx2 functions in adult retina. We show that this transcription factor is necessary for long-term maintenance of photoreceptors, likely through the control of specific activities of the RPE.

  6. Distinctive left-sided distribution of adrenergic-derived cells in the adult mouse heart.

    Directory of Open Access Journals (Sweden)

    Kingsley Osuala

    Full Text Available Adrenaline and noradrenaline are produced within the heart from neuronal and non-neuronal sources. These adrenergic hormones have profound effects on cardiovascular development and function, yet relatively little information is available about the specific tissue distribution of adrenergic cells within the adult heart. The purpose of the present study was to define the anatomical localization of cells derived from an adrenergic lineage within the adult heart. To accomplish this, we performed genetic fate-mapping experiments where mice with the cre-recombinase (Cre gene inserted into the phenylethanolamine-n-methyltransferase (Pnmt locus were cross-mated with homozygous Rosa26 reporter (R26R mice. Because Pnmt serves as a marker gene for adrenergic cells, offspring from these matings express the β-galactosidase (βGAL reporter gene in cells of an adrenergic lineage. βGAL expression was found throughout the adult mouse heart, but was predominantly (89% located in the left atrium (LA and ventricle (LV (p<0.001 compared to RA and RV, where many of these cells appeared to have cardiomyocyte-like morphological and structural characteristics. The staining pattern in the LA was diffuse, but the LV free wall displayed intermittent non-random staining that extended from the apex to the base of the heart, including heavy staining of the anterior papillary muscle along its perimeter. Three-dimensional computer-aided reconstruction of XGAL+ staining revealed distribution throughout the LA and LV, with specific finger-like projections apparent near the mid and apical regions of the LV free wall. These data indicate that adrenergic-derived cells display distinctive left-sided distribution patterns in the adult mouse heart.

  7. SKHIN/Sprd, a new genetically defined inbred hairless mouse strain for UV-induced skin carcinogenesis studies.

    Science.gov (United States)

    Perez, Carlos; Parker-Thornburg, Jan; Mikulec, Carol; Kusewitt, Donna F; Fischer, Susan M; Digiovanni, John; Conti, Claudio J; Benavides, Fernando

    2012-03-01

    Strains of mice vary in their susceptibility to ultra-violet (UV) radiation-induced skin tumors. Some strains of hairless mice (homozygous for the spontaneous Hr(hr) mutation) are particularly susceptible to these tumors. The skin tumors that develop in hairless mice resemble, both at the morphologic and molecular levels, UV-induced squamous cell carcinomas (SCC) and their precursors in human. The most commonly employed hairless mice belong to the SKH1 stock. However, these mice are outbred and their genetic background is not characterized, which makes them a poor model for genetic studies. We have developed a new inbred strain from outbred SKH1 mice that we named SKHIN/Sprd (now at generation F31). In order to characterize the genetic background of this new strain, we genotyped a cohort of mice at F30 with 92 microsatellites and 140 single nucleotide polymorphisms (SNP) evenly distributed throughout the mouse genome. We also exposed SKHIN/Sprd mice to chronic UV irradiation and showed that they are as susceptible to UV-induced skin carcinogenesis as outbred SKH1 mice. In addition, we proved that, albeit with low efficiency, inbred SKHIN/Sprd mice are suitable for transgenic production by classical pronuclear microinjection. This new inbred strain will be useful for the development of transgenic and congenic strains on a hairless inbred background as well as the establishment of syngeneic tumor cell lines. These new tools can potentially help elucidate a number of features of the cutaneous response to UV irradiation in humans, including the effect of genetic background and modifier genes.

  8. Dye-enhanced multimodal confocal microscopy for noninvasive detection of skin cancers in mouse models

    Science.gov (United States)

    Park, Jesung; Mroz, Pawel; Hamblin, Michael R.; Yaroslavsky, Anna N.

    2010-03-01

    Skin cancer is the most common form of human cancer. Its early diagnosis and timely treatment is of paramount importance for dermatology and surgical oncology. In this study, we evaluate the use of reflectance and fluorescence confocal microscopy for detecting skin cancers in an in-vivo trial with B16F10 melanoma and SCCVII squamous cell carcinoma in mice. For the experiments, the mice are anesthetized, then the tumors are infiltrated with aqueous solution of methylene blue and imaged. Reflectance images are acquired at 658 nm. Fluorescence is excited at 658 nm and registered in the range between 690 and 710 nm. After imaging, the mice are sacrificed. The tumors are excised and processed for hematoxylin and eosin histopathology, which is compared to the optical images. The results of the study indicate that in-vivo reflectance images provide valuable information on vascularization of the tumor, whereas the fluorescence images mimic the structural features seen in histopathology. Simultaneous dye-enhanced reflectance and fluorescence confocal microscopy shows promise for the detection, demarcation, and noninvasive monitoring of skin cancer development.

  9. UVB irradiation-enhanced zinc oxide nanoparticles-induced DNA damage and cell death in mouse skin.

    Science.gov (United States)

    Pal, Anu; Alam, Shamshad; Mittal, Sandeep; Arjaria, Nidhi; Shankar, Jai; Kumar, Mahadeo; Singh, Dhirendra; Pandey, Alok Kumar; Ansari, Kausar Mahmood

    2016-09-01

    UV-induced reactive oxygen species (ROS) have been implicated in photocarcinogenesis and skin aging. This is because UV-induced ROS can induce DNA damage that, if unrepaired, can lead to carcinogenesis. Sunscreens contain UV attenuators, such as organic chemical and/or physical UV filters, which can prevent all forms of damage from UV irradiation. In recent years, the effective broad-spectrum UV attenuation properties of ZnO-nanoparticles (ZnO-NPs) have made them attractive as active components in sunscreens and other personal care products. As the use of ZnO-NPs in sunscreens is on the rise, so is public concern about their safety, particularly with exposure to sunlight. Therefore, in the present study, using various experimental approaches, we investigated the possible toxic effects resulting from exposure to UVB and ZnO-NPs in primary mouse keratinocytes (PMKs) as well as in the skin of SKH-1 hairless mice. The findings of the present study demonstrated that co-exposure to UVB and ZnO-NPs: (1) translocated the ZnO-NPs into the nucleus of PMKs; (2) caused enhanced generation of ROS; (3) induced more severe DNA damage as evident by alkaline comet assay and immunocytochemistry for γ-H2AX and 8-hydroxy-2'-deoxyguanosine (8-OHdG); and (4) subsequently caused much more pronounced cell death in PMKs. Further, to elucidate the physiological relevance of these in vitro findings, SKH-1 hairless mice were topically treated with ZnO-NPs and after 30min irradiated with UVB (50mJ/cm(2)). Interestingly, we found that co-exposure of ZnO-NPs and UVB caused increased oxidative DNA damage and cell death, indicated by immunostaining for 8-OHdG and TUNEL assay in sections of exposed mouse skin. Thus, collectively, our findings suggest that UVB exposure increases ZnO-NPs-mediated oxidative stress and oxidative damage, thereby enhancing ZnO-NPs-induced cell death. PMID:27542711

  10. Ultrastructural Evidence of Exosome Secretion by Progenitor Cells in Adult Mouse Myocardium and Adult Human Cardiospheres

    Directory of Open Access Journals (Sweden)

    Lucio Barile

    2012-01-01

    Full Text Available The demonstration of beneficial effects of cell therapy despite the persistence of only few transplanted cells in vivo suggests secreted factors may be the active component of this treatment. This so-called paracrine hypothesis is supported by observations that culture media conditioned by progenitor cells contain growth factors that mediate proangiogenic and cytoprotective effects. Cardiac progenitor cells in semi-suspension culture form spherical clusters (cardiospheres that deliver paracrine signals to neighboring cells. A key component of paracrine secretion is exosomes, membrane vesicles that are stored intracellularly in endosomal compartments and are secreted when these structures fuse with the cell plasma membrane. Exosomes have been identified as the active component of proangiogenic effects of bone marrow CD34+ stem cells in mice and the regenerative effects of embryonic mesenchymal stem cells in infarcted hearts in pigs and mice. Here, we provide electron microscopic evidence of exosome secretion by progenitor cells in mouse myocardium and human cardiospheres. Exosomes are emerging as an attractive vector of paracrine signals delivered by progenitor cells. They can be stored as an “off-the-shelf” product. As such, exosomes have the potential for circumventing many of the limitations of viable cells for therapeutic applications in regenerative medicine.

  11. Oncostatin M overexpression induces skin inflammation but is not required in the mouse model of imiquimod-induced psoriasis-like inflammation.

    Science.gov (United States)

    Pohin, Mathilde; Guesdon, William; Mekouo, Adela Andrine Tagne; Rabeony, Hanitriniaina; Paris, Isabelle; Atanassov, Hristo; Favot, Laure; Mcheik, Jiad; Bernard, François-Xavier; Richards, Carl D; Amiaud, Jérôme; Blanchard, Frédéric; Lecron, Jean-Claude; Morel, Franck; Jégou, Jean-François

    2016-07-01

    Oncostatin M (OSM) has been reported to be overexpressed in psoriasis skin lesions and to exert proinflammatory effects in vitro on human keratinocytes. Here, we report the proinflammatory role of OSM in vivo in a mouse model of skin inflammation induced by intradermal injection of murine OSM-encoding adenovirus (AdOSM) and compare with that induced by IL-6 injection. Here, we show that OSM potently regulates the expression of genes involved in skin inflammation and epidermal differentiation in murine primary keratinocytes. In vivo, intradermal injection of AdOSM in mouse ears provoked robust skin inflammation with epidermal thickening and keratinocyte proliferation, while minimal effect was observed after AdIL-6 injection. OSM overexpression in the skin increased the expression of the S100A8/9 antimicrobial peptides, CXCL3, CCL2, CCL5, CCL20, and Th1/Th2 cytokines, in correlation with neutrophil and macrophage infiltration. In contrast, OSM downregulated the expression of epidermal differentiation genes, such as cytokeratin-10 or filaggrin. Collectively, these results support the proinflammatory role of OSM when it is overexpressed in the skin. However, OSM expression was not required in the murine model of psoriasis induced by topical application of imiquimod, as demonstrated by the inflammatory phenotype of OSM-deficient mice or wild-type mice treated with anti-OSM antibodies. PMID:27122058

  12. Inhibition of akt enhances the chemopreventive effects of topical rapamycin in mouse skin

    Science.gov (United States)

    Dickinson, Sally E; Janda, Jaroslav; Criswell, Jane; Blohm-Mangone, Karen; Olson, Erik R.; Liu, Zhonglin; Barber, Christie; Rusche, Jadrian J.; Petricoin, Emmanuel; Calvert, Valerie; Einspahr, Janine G.; Dickinson, Jesse; Stratton, Steven P.; Curiel-Lewandrowski, Clara; Saboda, Kathylynn; Hu, Chengcheng; Bode, Ann M.; Dong, Zigang; Alberts, David S.; Bowden, G. Timothy

    2016-01-01

    The PI3Kinase/Akt/mTOR pathway has important roles in cancer development for multiple tumor types, including UV-induced non-melanoma skin cancer. Immunosuppressed populations are at increased risk of aggressive cutaneous squamous cell carcinoma (SCC). Individuals who are treated with rapamycin, (sirolimus, a classical mTOR inhibitor) have significantly decreased rates of developing new cutaneous SCCs compared to those that receive traditional immunosuppression. However, systemic rapamycin use can lead to significant adverse events. Here we explored the use of topical rapamycin as a chemopreventive agent in the context of solar simulated light (SSL)-induced skin carcinogenesis. In SKH-1 mice, topical rapamycin treatment decreased tumor yields when applied after completion of 15 weeks of SSL exposure compared to controls. However, applying rapamycin during SSL exposure for 15 weeks, and continuing for 10 weeks after UV treatment, increased tumor yields. We also examined whether a combinatorial approach might result in more significant tumor suppression by rapamycin. We validated that rapamycin causes increased Akt (S473) phosphorylation in the epidermis after SSL, and show for the first time that this dysregulation can be inhibited in vivo by a selective PDK1/Akt inhibitor, PHT-427. Combining rapamycin with PHT-427 on tumor prone skin additively caused a significant reduction of tumor multiplicity compared to vehicle controls. Our findings indicate that patients taking rapamycin should avoid sun exposure, and that combining topical mTOR inhibitors and Akt inhibitors may be a viable chemoprevention option for individuals at high risk for cutaneous SCC.

  13. Effect of glycyrrhizin on pseudomonal skin infections in human-mouse chimeras.

    Science.gov (United States)

    Yoshida, Shohei; Lee, Jong O; Nakamura, Kiwamu; Suzuki, Sumihiro; Hendon, David N; Kobayashi, Makiko; Suzuki, Fujio

    2014-01-01

    In our previous studies, peripheral blood lineage(-)CD34(+)CD31(+) cells (CD31(+) IMC) appearing in severely burned patients have been characterized as inhibitor cells for the production of β-defensins (HBDs) by human epidermal keratinocytes (NHEK). In this study, the effect of glycyrrhizin on pseudomonal skin infections was studied in a chimera model of thermal injury. Two different chimera models were utilized. Patient chimeras were created in murine antimicrobial peptide-depleted NOD-SCID IL-2rγ(null) mice that were grafted with unburned skin tissues of severely burned patients and inoculated with the same patient peripheral blood CD31(+) IMC. Patient chimera substitutes were created in the same mice that were grafted with NHEK and inoculated with experimentally induced CD31(+) IMC. In the results, both groups of chimeras treated with glycyrrhizin resisted a 20 LD50 dose of P. aeruginosa skin infection, while all chimeras in both groups treated with saline died within 3 days of the infection. Human antimicrobial peptides were detected from the grafted site tissues of both groups of chimeras treated with glycyrrhizin, while the peptides were not detected in the same area tissues of controls. HBD-1 was produced by keratinocytes in transwell-cultures performed with CD31(+) IMC and glycyrrhizin. Also, inhibitors (IL-10 and CCL2) of HBD-1 production by keratinocytes were not detected in cultures of patient CD31(+) IMC treated with glycyrrhizin. These results indicate that sepsis stemming from pseudomonal grafted site infections in a chimera model of burn injury is controllable by glycyrrhizin. Impaired antimicrobial peptide production at the infection site of severely burned patients may be restored after treatment with glycyrrhizin. PMID:24497916

  14. Effect of glycyrrhizin on pseudomonal skin infections in human-mouse chimeras.

    Directory of Open Access Journals (Sweden)

    Shohei Yoshida

    Full Text Available In our previous studies, peripheral blood lineage(-CD34(+CD31(+ cells (CD31(+ IMC appearing in severely burned patients have been characterized as inhibitor cells for the production of β-defensins (HBDs by human epidermal keratinocytes (NHEK. In this study, the effect of glycyrrhizin on pseudomonal skin infections was studied in a chimera model of thermal injury. Two different chimera models were utilized. Patient chimeras were created in murine antimicrobial peptide-depleted NOD-SCID IL-2rγ(null mice that were grafted with unburned skin tissues of severely burned patients and inoculated with the same patient peripheral blood CD31(+ IMC. Patient chimera substitutes were created in the same mice that were grafted with NHEK and inoculated with experimentally induced CD31(+ IMC. In the results, both groups of chimeras treated with glycyrrhizin resisted a 20 LD50 dose of P. aeruginosa skin infection, while all chimeras in both groups treated with saline died within 3 days of the infection. Human antimicrobial peptides were detected from the grafted site tissues of both groups of chimeras treated with glycyrrhizin, while the peptides were not detected in the same area tissues of controls. HBD-1 was produced by keratinocytes in transwell-cultures performed with CD31(+ IMC and glycyrrhizin. Also, inhibitors (IL-10 and CCL2 of HBD-1 production by keratinocytes were not detected in cultures of patient CD31(+ IMC treated with glycyrrhizin. These results indicate that sepsis stemming from pseudomonal grafted site infections in a chimera model of burn injury is controllable by glycyrrhizin. Impaired antimicrobial peptide production at the infection site of severely burned patients may be restored after treatment with glycyrrhizin.

  15. Nogo-A is a reliable oligodendroglial marker in adult human and mouse CNS and in demyelinated lesions

    DEFF Research Database (Denmark)

    Kuhlmann, Tanja; Remington, Leah; Maruschak, Brigitte;

    2007-01-01

    to be strongly expressed in mature oligodendrocytes in vivo. In the present investigation we analyzed the expression patterns of Nogo-A in adult mouse and human CNS as well as in demyelinating animal models and multiple sclerosis lesions. Nogo-A expression was compared with that of other frequently used...... oligodendroglial markers such as CC1, CNP, and in situ hybridization for proteolipid protein mRNA. Nogo-A strongly and reliably labeled oligodendrocytes in the adult CNS as well as in demyelinating lesions and thus represents a valuable tool for the identification of oligodendrocytes in human and mouse CNS tissue...... Udgivelsesdato: 2007-Mar...

  16. Recombinant Goat VEGF164 Increases Hair Growth by Painting Process on the Skin of Shaved Mouse.

    Science.gov (United States)

    Bao, Wenlei; Yin, Jianxin; Liang, Yan; Guo, Zhixin; Wang, Yanfeng; Liu, Dongjun; Wang, Xiao; Wang, Zhigang

    2014-09-01

    To detect goat vascular endothelial growth factor (VEGF)-mediated regrowth of hair, full-length VEGF164 cDNA was cloned from Inner Mongolia cashmere goat (Capra hircus) into the pET-his prokaryotic expression vector, and the recombinant plasmid was transferred into E. coli BL21 cells. The expression of recombinant 6×his-gVEGF164 protein was induced by 0.5 mM isopropyl thio-β-D-galactoside at 32°C. Recombinant goat VEGF164 (rgVEGF164) was purified and identi ed by western blot using monoclonal anti-his and anti-VEGF antibodies. The rgVEGF164 was smeared onto the dorsal area of a shaved mouse, and we noted that hair regrowth in this area was faster than in the control group. Thus, rgVEGF164 increases hair growth in mice. PMID:25178380

  17. Modulatory influence of Rosemarinus officinalis on DMBA-induced mouse skin tumorigenesis.

    Science.gov (United States)

    Sancheti, Garima; Goyal, Pk

    2006-01-01

    The present investigation was undertaken to explore the anti-tumor promoting activity of Rosemarinus officinalis on two-stage skin carcinogenesis, induced by a single topical application of 7, 12-dimethylbenz(a)anthracene and promoted by treatment of croton oil for 15 weeks in Swiss albino mice. Oral administration of Rosemary leaf extract at a dose of 1,000 mg/ kg b. wt. / day at pre, peri and post-initiational phases, was found to be effective in decreasing the tumor incidence (50, 41.7, 58.3%, respectively) in comparison to the control (100%). Furthermore, the cumulative number of papillomas, tumor yield and tumor burden were also found to be reduced in R. officinalis-treated animals. This was associated with significant alteration in liver lipid peroxidation and glutathione (GSH) levels. PMID:16839234

  18. Abca7 deletion does not affect adult neurogenesis in the mouse.

    Science.gov (United States)

    Li, Hongyun; Karl, Tim; Garner, Brett

    2016-01-01

    ATP-binding cassette transporter A7 (ABCA7) is highly expressed in the brain. Recent genome-wide association studies (GWAS) have identified ABCA7 single nucleotide polymorphisms (SNPs) that increase Alzheimer's disease (AD) risk, however, the mechanisms by which ABCA7 may control AD risk remain to be fully elucidated. Based on previous research suggesting that certain ABC transporters may play a role in the regulation of neurogenesis, we conducted a study of cell proliferation and neurogenic potential using cellular bromodeoxyuridine (BrdU) incorporation and doublecortin (DCX) immunostaining in adult Abca7 deficient mice and wild-type-like (WT) littermates. In the present study counting of BrdU-positive and DCX-positive cells in an established adult neurogenesis site in the dentate gyrus (DG) indicated there were no significant differences when WT and Abca7 deficient mice were compared. We also measured the area occupied by immunohistochemical staining for BrdU and DCX in the DG and the subventricular zone (SVZ) of the same mice and this confirmed that ABCA7 does not play a significant role in the regulation of cell proliferation or neurogenesis in the adult mouse. PMID:26792809

  19. Characterization of neural stem cells and their progeny in the sensory circumventricular organs of adult mouse.

    Science.gov (United States)

    Furube, Eriko; Morita, Mitsuhiro; Miyata, Seiji

    2015-11-01

    Although evidence has accumulated that neurogenesis and gliogenesis occur in the subventricular zone (SVZ) and subgranular zone (SGZ) of adult mammalian brains, recent studies indicate the presence of neural stem cells (NSCs) in adult brains, particularly the circumventricular regions. In the present study, we aimed to determine characterization of NSCs and their progenitor cells in the sensory circumventricular organs (CVOs), including organum vasculosum of the lamina terminalis, subfornical organ, and area postrema of adult mouse. There were two types of NSCs: tanycyte-like ependymal cells and astrocyte-like cells. Astrocyte-like NSCs proliferated slowly and oligodendrocyte progenitor cells (OPCs) and neural progenitor cells (NPCs) actively divided. Molecular marker protein expression of NSCs and their progenitor cells were similar to those reported in the SVZ and SGZ, except that astrocyte-like NSCs expressed S100β. These circumventricular NSCs possessed the capacity to give rise to oligodendrocytes and sparse numbers of neurons and astrocytes in the sensory CVOs and adjacent brain regions. The inhibition of vascular endothelial growth factor (VEGF) signaling by using a VEGF receptor-associated tyrosine kinase inhibitor AZD2171 largely suppressed basal proliferation of OPCs. A single systemic administration of lipopolysaccharide attenuated proliferation of OPCs and induced remarkable proliferation of microglia. The present study indicates that sensory circumventricular NSCs provide new neurons and glial cells in the sensory CVOs and adjacent brain regions. PMID:25994374

  20. Solar-UV-signature mutation prefers TCG to CCG: extrapolative consideration from UVA1-induced mutation spectra in mouse skin.

    Science.gov (United States)

    Ikehata, Hironobu; Kumagai, Jun; Ono, Tetsuya; Morita, Akimichi

    2013-08-01

    UVA1 exerts its genotoxicity on mammalian skin by producing cyclobutane pyrimidine dimers (CPDs) in DNA and preferentially inducing solar-UV-signature mutations, C → T base substitution mutations at methylated CpG-associated dipyrimidine (Py-mCpG) sites, as demonstrated previously using a 364 nm laser as a UVA1 source and lacZ-transgenic mice that utilize the transgene as a mutational reporter. In the present study, we confirmed that a broadband UVA1 source induced the same mutation profiles in mouse epidermis as the UVA1 laser, generalizing the previous result from a single 364 nm to a wider wavelength range of UVA1 (340-400 nm). Combined with our previous data on the mutation spectra induced in mouse epidermis by UVB, UVA2 and solar UVR, we proved that the solar-UV-signature mutation is commonly observed in the wavelength range from UVB to UVA, and found that UVA1 induces this mutation more preferentially than the other shorter wavelength ranges. This finding indicates that the solar-UV-signature mutation-causing CPDs, which are known to prefer Py-mCpG sites, could be produced with the energy provided by the longer wavelength region of UVR, suggesting a photochemical reaction through the excitation of pyrimidine bases to energy states that can be accomplished by absorption of even low-energy UVR. On the other hand, the lower proportions of solar-UV-signature mutations observed in the mutation spectra for UVB and solar UVR indicate that the direct photochemical reaction through excited singlet state of pyrimidine bases, which can be accomplished only by high-energy UVR, is also involved in the mutation induction at those shorter wavelengths of UVR. We also found that the solar-UV signature prefers 5'-TCG-3' to 5'-CCG-3' as mutational target sites, consistent with the fact that UVA induces CPDs selectively at thymine-containing dipyrimidine sites and that solar UVR induces them preferably at Py-mCpG sites. However, the mutation spectrum in human p53 gene from non

  1. Assessment of reinforced poly(ethylene glycol) chitosan hydrogels as dressings in a mouse skin wound defect model

    International Nuclear Information System (INIS)

    Wound dressings of chitosan are biocompatible, biodegradable, antibacterial and hemostatic biomaterials. However, applications for chitosan are limited due to its poor mechanical properties. Here, we conducted an in vivo mouse angiogenesis study on reinforced poly(ethylene glycol) (PEG)-chitosan (RPC) hydrogels. RPC hydrogels were formed by cross-linking chitosan with PEGs of different molecular weights at various PEG to chitosan ratios in our previous paper. These dressings can keep the wound moist, had good gas exchange capacity, and was capable of absorbing or removing the wound exudate. We examined the ability of these RPC hydrogels and neat chitosan to heal small cuts and full-thickness skin defects on the backs of male Balb/c mice. Histological examination revealed that chitosan suppressed the infiltration of inflammatory cells and accelerated fibroblast proliferation, while PEG enhanced epithelial migration. The RPC hydrogels promoted wound healing in the small cuts and full layer wounds. The optimal RPC hydrogel had a swelling ratio of 100% and a water vapor transmission rate (WVTR) of about 2000 g/m2/day. In addition, they possess good mechanical property and appropriate degradation rates. Thus, the optimal RPC hydrogel formulation functioned effectively as a wound dressing and promoted wound healing. Highlights: ► Mouse angiogenesis study on reinforced poly(ethylene glycol)-chitosan (RPC) ► Water vapor transmission rate of about 2000 g/m2/day is characteristic of RPC. ► RPC suppressed inflammatory cells and accelerated fibroblast proliferation. ► RPC composed of 1000-RP10C90 can be used as a biomaterial for wound dressing

  2. Assessment of reinforced poly(ethylene glycol) chitosan hydrogels as dressings in a mouse skin wound defect model

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Szu-Hsien [Institute of Polymer Science and Engineering, College of Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei City 10617, Taiwan (China); Tsao, Ching-Ting [Institute of Polymer Science and Engineering, College of Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei City 10617, Taiwan (China); Epithelial Biology Laboratory/Transgenic Mice Core-Laboratory, Department of Anatomy, Chang Gung University, Taoyuan 33302, Taiwan (China); Chang, Chih-Hao [Department of Orthopedics, National Taiwan University Hospital, Taiwan (China); National Taiwan University College of Medicine, No. 1, Jen-Ai Road, Taipei City 10018, Taiwan (China); Lai, Yi-Ting [Department of Chemical Engineering, College of Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei City 10617, Taiwan (China); Wu, Ming-Fung [Animal Medicine Center, College of Medicine, National Taiwan University, No. 1, Jen-Ai Road, Taipei City 10018, Taiwan (China); Chuang, Ching-Nan [Institute of Polymer Science and Engineering, College of Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei City 10617, Taiwan (China); Chou, Hung-Chia [Department of Chemical Engineering, College of Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei City 10617, Taiwan (China); Wang, Chih-Kuang, E-mail: ckwang@kmu.edu.tw [Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan (China); Hsieh, Kuo-Haung, E-mail: khhsieh@ntu.edu.tw [Institute of Polymer Science and Engineering, College of Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei City 10617, Taiwan (China)

    2013-07-01

    Wound dressings of chitosan are biocompatible, biodegradable, antibacterial and hemostatic biomaterials. However, applications for chitosan are limited due to its poor mechanical properties. Here, we conducted an in vivo mouse angiogenesis study on reinforced poly(ethylene glycol) (PEG)-chitosan (RPC) hydrogels. RPC hydrogels were formed by cross-linking chitosan with PEGs of different molecular weights at various PEG to chitosan ratios in our previous paper. These dressings can keep the wound moist, had good gas exchange capacity, and was capable of absorbing or removing the wound exudate. We examined the ability of these RPC hydrogels and neat chitosan to heal small cuts and full-thickness skin defects on the backs of male Balb/c mice. Histological examination revealed that chitosan suppressed the infiltration of inflammatory cells and accelerated fibroblast proliferation, while PEG enhanced epithelial migration. The RPC hydrogels promoted wound healing in the small cuts and full layer wounds. The optimal RPC hydrogel had a swelling ratio of 100% and a water vapor transmission rate (WVTR) of about 2000 g/m{sup 2}/day. In addition, they possess good mechanical property and appropriate degradation rates. Thus, the optimal RPC hydrogel formulation functioned effectively as a wound dressing and promoted wound healing. Highlights: ► Mouse angiogenesis study on reinforced poly(ethylene glycol)-chitosan (RPC) ► Water vapor transmission rate of about 2000 g/m{sup 2}/day is characteristic of RPC. ► RPC suppressed inflammatory cells and accelerated fibroblast proliferation. ► RPC composed of 1000-RP10C90 can be used as a biomaterial for wound dressing.

  3. Skin vaccination against cervical cancer associated human papillomavirus with a novel micro-projection array in a mouse model.

    Directory of Open Access Journals (Sweden)

    Holly J Corbett

    Full Text Available BACKGROUND: Better delivery systems are needed for routinely used vaccines, to improve vaccine uptake. Many vaccines contain alum or alum based adjuvants. Here we investigate a novel dry-coated densely-packed micro-projection array skin patch (Nanopatch™ as an alternate delivery system to intramuscular injection for delivering an alum adjuvanted human papillomavirus (HPV vaccine (Gardasil® commonly used as a prophylactic vaccine against cervical cancer. METHODOLOGY/PRINCIPAL FINDINGS: Micro-projection arrays dry-coated with vaccine material (Gardasil® delivered to C57BL/6 mouse ear skin released vaccine within 5 minutes. To assess vaccine immunogenicity, doses of corresponding to HPV-16 component of the vaccine between 0.43 ± 0.084 ng and 300 ± 120 ng (mean ± SD were administered to mice at day 0 and day 14. A dose of 55 ± 6.0 ng delivered intracutaneously by micro-projection array was sufficient to produce a maximal virus neutralizing serum antibody response at day 28 post vaccination. Neutralizing antibody titres were sustained out to 16 weeks post vaccination, and, for comparable doses of vaccine, somewhat higher titres were observed with intracutaneous patch delivery than with intramuscular delivery with the needle and syringe at this time point. CONCLUSIONS/SIGNIFICANCE: Use of dry micro-projection arrays (Nanopatch™ has the potential to overcome the need for a vaccine cold chain for common vaccines currently delivered by needle and syringe, and to reduce risk of needle-stick injury and vaccine avoidance due to the fear of the needle especially among children.

  4. Attenuation of DMBA/croton oil induced mouse skin papilloma by Apodytes dimidiata mediated by its antioxidant and antimutagenic potential.

    Science.gov (United States)

    Divya, Menon K; Salini, Sasidharan; Meera, Nair; Lincy, Lawrence; Seema, Menon; Raghavamenon, Achuthan C; Babu, Thekkekara D

    2016-09-01

    Context Considering the role of cellular oxidative stress in mutations and subsequent transformation, phytochemicals with antioxidant potential has become a primary choice as chemopreventives. Apodytes dimidiata E. Mey. Ex. Arn (Icacinaceae), a widely used plant in Zulu traditional medicine, is reported to possess antioxidant activity. Objective To investigate the chemopreventive efficacy of methanol extract of A. dimidiata leaf (AMF). Materials and methods Antimutagenic potential of AMF (25, 50 and 75 μg/plate) was evaluated by the Ames test. The ability of AMF (100 and 250 mg/kg orally) on restoration of depleted antioxidant status by sodium fluoride (NaF) was analysed on BALB/c mice. 7,12-Dimethylbenz[a]anthracene/croton oil induced mouse skin papilloma model was studied up to 20 weeks to analyse the anticarcinogenic effect of AMF (1%, 3% and 5% topically, twice weekly for 6 weeks). Phytochemicals of AMF were characterized by GC-MS. Results AMF (75 μg/plate) reverted 4-nitro-o-phenylenediamine (NPDA) induced mutations in Salmonella typhimurium strains, TA 98, 100 and 102 by 74.8%, 72.5% and 69.3%, respectively. Against sodium azide, the percentage reversion was 80.4, 71.3 and 71.3. In mice, AMF (250 mg/kg for 4 days) increased the serum superoxide dismutase (SOD) and catalase activities by 48.71% and 30.3% against the NaF-induced drop. GSH level was improved by 48.59% with a concomitant decrease in TBARS (57.67%). The skin papilloma reduction was 79.32% for 5% AMF. Squalene, dodecanoic, tetradecanoic and hexadecanoic acids are the known antioxidant and chemopreventive molecules identified by GC-MS. Discussion and conclusion Antioxidant and antimutagenic activities of AMF might have contributed to its anticarcinogenic potential. PMID:26878464

  5. Increased Skin Tumor Incidence and Keratinocyte Hyper-Proliferation in a Mouse Model of Down Syndrome.

    Science.gov (United States)

    Yang, Annan; Currier, Duane; Poitras, Jennifer L; Reeves, Roger H

    2016-01-01

    Down syndrome (DS) is a genetic disorder caused by the presence of an extra copy of human chromosome 21 (Hsa21). People with DS display multiple clinical traits as a result of the dosage imbalance of several hundred genes. While many outcomes of trisomy are deleterious, epidemiological studies have shown a significant risk reduction for most solid tumors in DS. Reduced tumor incidence has also been demonstrated in functional studies using trisomic DS mouse models. Therefore, it was interesting to find that Ts1Rhr trisomic mice developed more papillomas than did their euploid littermates in a DMBA-TPA chemical carcinogenesis paradigm. Papillomas in Ts1Rhr mice also proliferated faster. The increased proliferation was likely caused by a stronger response of trisomy to TPA induction. Treatment with TPA caused hyperkeratosis to a greater degree in Ts1Rhr mice than in euploid, reminiscent of hyperkeratosis seen in people with DS. Cultured trisomic keratinocytes also showed increased TPA-induced proliferation compared to euploid controls. These outcomes suggest that altered gene expression in trisomy could elevate a proliferation signalling pathway. Gene expression analysis of cultured keratinocytes revealed upregulation of several trisomic and disomic genes may contribute to this hyperproliferation. The contributions of these genes to hyper-proliferation were further validated in a siRNA knockdown experiment. The unexpected findings reported here add a new aspect to our understanding of tumorigenesis with clinical implications for DS and demonstrates the complexity of the tumor repression phenotype in this frequent condition.

  6. Expression profiling of long noncoding RNAs in neonatal and adult mouse testis

    Directory of Open Access Journals (Sweden)

    Jin Sun

    2015-09-01

    Full Text Available In recent years, advancements in genome-wide analyses of the mammalian transcriptome have revealed that long noncoding RNAs (lncRNAs is pervasively transcribed in the genome and an increasing number of studies have demonstrated lncRNAs as a new class of regulatory molecules are involved in mammalian development (Carninci et al. (2005; Fatica and Bozzoni (2014, but very few studies have been conducted on the potential roles of lncRNAs in mammalian testis development. To get insights into the expression patterns of lncRNA during mouse testis development, we investigated the lncRNAs expression profiles of neonatal and adult mouse testes using microarray platform and related results have been published (Sun et al., PLoS One 8 (2013 e75750.. Here, we describe in detail the experimental system, methods and validation for the generation of the microarray data associated with our recent publication (Sun et al., PLoS One 8 (2013 e75750.. Data have been deposited to the Gene Expression Omnibus (GEO database repository with the dataset identifier GSE43442.

  7. Expression profile of microRNAs regulating proliferation and differentiation in mouse adult cardiac stem cells.

    Directory of Open Access Journals (Sweden)

    Luis Brás-Rosário

    Full Text Available The identification of cardiac cells with stem cell properties changed the paradigm of the heart as a post mitotic organ. These cells proliferate and differentiate into cardiomyocytes, endothelial and vascular smooth muscle cells, providing for cardiac cell homeostasis and regeneration. microRNAs are master switches controlling proliferation and differentiation, in particular regulating stem cell biology and cardiac development. Modulation of microRNAs -regulated gene expression networks holds the potential to control cell fate and proliferation, with predictable biotechnologic and therapeutic applications. To obtain insights into the regulatory networks active in cardiac stem cells, we characterized the expression profile of 95 microRNAs with reported functions in stem cell and tissue differentiation in mouse cardiac stem cells, and compared it to that of mouse embryonic heart and mesenchymal stem cells. The most highly expressed microRNAs identified in cardiac stem cells are known to target key genes involved in the control of cell proliferation and adhesion, vascular function and cardiomyocyte differentiation. We report a subset of differentially expressed microRNAs that are proposed to act as regulators of differentiation and proliferation of adult cardiac stem cells, providing novel insights into active gene expression networks regulating their biological properties.

  8. Chronic morphine induces premature mitosis of proliferating cells in the adult mouse subgranular zone.

    Science.gov (United States)

    Mandyam, Chitra D; Norris, Rebekah D; Eisch, Amelia J

    2004-06-15

    The birth of cells with neurogenic potential in the adult brain is assessed commonly by detection of exogenous S phase markers, such as bromodeoxyuridine (BrdU). Analysis of other phases of the cell cycle, however, can provide insight into how external factors, such as opiates, influence the cycling of newly born cells. To this end, we examined the expression of two endogenous cell cycle markers in relation to BrdU: proliferating cell nuclear antigen (PCNA) and phosphorylated histone H3 (pHisH3). Two hours after one intraperitoneal BrdU injection, BrdU-, PCNA-, and pHisH3-immunoreactive (IR) cells exhibited similar distribution in the adult mouse subgranular zone (SGZ). Quantitative analysis within the SGZ revealed a relative abundance of cells labeled for PCNA > BrdU > pHisH3. Similar to our reports in rat SGZ, chronic morphine treatment decreased BrdU- and PCNA-IR cells in mouse SGZ by 28 and 38%, respectively. We also show that pHisH3-IR cells are influenced by chronic morphine to a greater extent (58% decrease) than are BrdU- or PCNA-IR cells. Cell cycle phase analysis of SGZ BrdU-IR cells using triple labeling for BrdU, PCNA, and pHisH3 revealed premature mitosis in chronic morphine-treated mice. These results suggest that morphine-treated mice have a shorter Gap2/mitosis (G(2)/M) phase when compared to sham-treated mice. These findings demonstrate the power of using a combination of exogenous and endogenous cell cycle markers and nuclear morphology to track proliferating cells through different phases of the cell cycle and to reveal the regulation of cell cycle phase by chronic morphine. PMID:15160390

  9. Meis1 Is Required for Adult Mouse Erythropoiesis, Megakaryopoiesis and Hematopoietic Stem Cell Expansion.

    Science.gov (United States)

    Miller, Michelle Erin; Rosten, Patty; Lemieux, Madeleine E; Lai, Courteney; Humphries, R Keith

    2016-01-01

    Meis1 is recognized as an important transcriptional regulator in hematopoietic development and is strongly implicated in the pathogenesis of leukemia, both as a Hox transcription factor co-factor and independently. Despite the emerging recognition of Meis1's importance in the context of both normal and leukemic hematopoiesis, there is not yet a full understanding of Meis1's functions and the relevant pathways and genes mediating its functions. Recently, several conditional mouse models for Meis1 have been established. These models highlight a critical role for Meis1 in adult mouse hematopoietic stem cells (HSCs) and implicate reactive oxygen species (ROS) as a mediator of Meis1 function in this compartment. There are, however, several reported differences between these studies in terms of downstream progenitor populations impacted and effectors of function. In this study, we describe further characterization of a conditional knockout model based on mice carrying a loxP-flanked exon 8 of Meis1 which we crossed onto the inducible Cre localization/expression strains, B6;129-Gt(ROSA)26Sor(tm1(Cre/ERT)Nat)/J or B6.Cg-Tg(Mx1-Cre)1Cgn/J. Findings obtained from these two inducible Meis1 knockout models confirm and extend previous reports of the essential role of Meis1 in adult HSC maintenance and expansion and provide new evidence that highlights key roles of Meis1 in both megakaryopoiesis and erythropoiesis. Gene expression analyses point to a number of candidate genes involved in Meis1's role in hematopoiesis. Our data additionally support recent evidence of a role of Meis1 in ROS regulation. PMID:26986211

  10. Nitisinone improves eye and skin pigmentation defects in a mouse model of oculocutaneous albinism.

    Science.gov (United States)

    Onojafe, Ighovie F; Adams, David R; Simeonov, Dimitre R; Zhang, Jun; Chan, Chi-Chao; Bernardini, Isa M; Sergeev, Yuri V; Dolinska, Monika B; Alur, Ramakrishna P; Brilliant, Murray H; Gahl, William A; Brooks, Brian P

    2011-10-01

    Mutation of the tyrosinase gene (TYR) causes oculocutaneous albinism, type 1 (OCA1), a condition characterized by reduced skin and eye melanin pigmentation and by vision loss. The retinal pigment epithelium influences postnatal visual development. Therefore, increasing ocular pigmentation in patients with OCA1 might enhance visual function. There are 2 forms of OCA1, OCA-1A and OCA-1B. Individuals with the former lack functional tyrosinase and therefore lack melanin, while individuals with the latter produce some melanin. We hypothesized that increasing plasma tyrosine concentrations using nitisinone, an FDA-approved inhibitor of tyrosine degradation, could stabilize tyrosinase and improve pigmentation in individuals with OCA1. Here, we tested this hypothesis in mice homozygous for either the Tyrc-2J null allele or the Tyrc-h allele, which model OCA-1A and OCA-1B, respectively. Only nitisinone-treated Tyrc-h/c-h mice manifested increased pigmentation in their fur and irides and had more pigmented melanosomes. High levels of tyrosine improved the stability and enzymatic function of the Tyrc-h protein and also increased overall melanin levels in melanocytes from a human with OCA-1B. These results suggest that the use of nitisinone in OCA-1B patients could improve their pigmentation and potentially ameliorate vision loss. PMID:21968110

  11. Riboflavin as adjuvant with cisplatin: study in mouse skin cancer model.

    Science.gov (United States)

    Salman, Maria; Naseem, Imrana

    2015-01-01

    Cisplatin used in treatment of solid tumor induces oxidative stress which leads to hepatotoxicity and nephrotoxicity. New strategies are therefore needed to combat toxicity and optimize its therapeutic potential. Riboflavin (VitaminB2) under photoillumination works as an anti proliferative agent and induces apoptosis. These properties of riboflavin have been exploited to mitigate cisplatin induced toxicities. 9,10-dimethylbenz(a)anthracene /12-O-tetradecanoylphorbol-13-acetate  were used to induce skin tumor in Swiss albino mice. The tumor induced mice were treated with cisplatin, riboflavin as well as their combination under photo illumination. In comparison to tumor control group the cisplatin and riboflavin treated groups showed a compromised level of antioxidant enzymes, functional markers and a higher degree of lipid peroxidation. However these parameters tended towards normal in the combination treated group. The results from histopathology indicate that apoptosis was favored mode of cell death and that necrosis was reduced in combination treated groups. Our findings indicate that combination of cisplatin with riboflavin under photo illumination synergizes its anti cancer activity towards cancer cells and attenuates the cisplatin induced toxicities.

  12. Overexpression of galectin-7 in mouse epidermis leads to loss of cell junctions and defective skin repair.

    Directory of Open Access Journals (Sweden)

    Gaëlle Gendronneau

    Full Text Available The proteins of the galectin family are implicated in many cellular processes, including cell interactions, polarity, intracellular trafficking, and signal transduction. In human and mouse, galectin-7 is almost exclusively expressed in stratified epithelia, notably in the epidermis. Galectin-7 expression is also altered in several human tumors of epithelial origin. This study aimed at dissecting the consequences of galectin-7 overexpression on epidermis structure and functions in vivo.We established transgenic mice specifically overexpressing galectin-7 in the basal epidermal keratinocytes and analyzed the consequences on untreated skin and after UVB irradiation or mechanical injury.The intercellular cohesion of the epidermis is impaired in transgenic animals, with gaps developing between adjacent keratinocytes, associated with loss of adherens junctions. The epidermal architecture is aberrant with perturbations in the multilayered cellular organisation of the tissue, and structural defects in the basement membrane. These transgenic animals displayed a reduced re-epithelialisation potential following superficial wound, due to a defective collective migration of keratinocytes. Finally, a single mild dose of UVB induced an abnormal apoptotic response in the transgenic epidermis.These results indicate that an excess of galectin-7 leads to a destabilisation of adherens junctions associated with defects in epidermal repair. As this phenotype shares similarities with that of galectin-7 null mutant mice, we conclude that a critical level of this protein is required for maintaining proper epidermal homeostasis. This study brings new insight into the mode of action of galectins in normal and pathological situations.

  13. Assessment of reinforced poly(ethylene glycol) chitosan hydrogels as dressings in a mouse skin wound defect model.

    Science.gov (United States)

    Chen, Szu-Hsien; Tsao, Ching-Ting; Chang, Chih-Hao; Lai, Yi-Ting; Wu, Ming-Fung; Chuang, Ching-Nan; Chou, Hung-Chia; Wang, Chih-Kuang; Hsieh, Kuo-Haung

    2013-07-01

    Wound dressings of chitosan are biocompatible, biodegradable, antibacterial and hemostatic biomaterials. However, applications for chitosan are limited due to its poor mechanical properties. Here, we conducted an in vivo mouse angiogenesis study on reinforced poly(ethylene glycol) (PEG)-chitosan (RPC) hydrogels. RPC hydrogels were formed by cross-linking chitosan with PEGs of different molecular weights at various PEG to chitosan ratios in our previous paper. These dressings can keep the wound moist, had good gas exchange capacity, and was capable of absorbing or removing the wound exudate. We examined the ability of these RPC hydrogels and neat chitosan to heal small cuts and full-thickness skin defects on the backs of male Balb/c mice. Histological examination revealed that chitosan suppressed the infiltration of inflammatory cells and accelerated fibroblast proliferation, while PEG enhanced epithelial migration. The RPC hydrogels promoted wound healing in the small cuts and full layer wounds. The optimal RPC hydrogel had a swelling ratio of 100% and a water vapor transmission rate (WVTR) of about 2000 g/m(2)/day. In addition, they possess good mechanical property and appropriate degradation rates. Thus, the optimal RPC hydrogel formulation functioned effectively as a wound dressing and promoted wound healing.

  14. PPARs Expression in Adult Mouse Neural Stem Cells: Modulation of PPARs during Astroglial Differentiaton of NSC

    Directory of Open Access Journals (Sweden)

    A. Cimini

    2007-01-01

    Full Text Available PPAR isotypes are involved in the regulation of cell proliferation, death, and differentiation, with different roles and mechanisms depending on the specific isotype and ligand and on the differentiated, undifferentiated, or transformed status of the cell. Differentiation stimuli are integrated by key transcription factors which regulate specific sets of specialized genes to allow proliferative cells to exit the cell cycle and acquire specialized functions. The main differentiation programs known to be controlled by PPARs both during development and in the adult are placental differentiation, adipogenesis, osteoblast differentiation, skin differentiation, and gut differentiation. PPARs may also be involved in the differentiation of macrophages, brain, and breast. However, their functions in this cell type and organs still awaits further elucidation. PPARs may be involved in cell proliferation and differentiation processes of neural stem cells (NSC. To this aim, in this work the expression of the three PPAR isotypes and RXRs in NSC has been investigated.

  15. 2,6-Dithiopurine, a nucleophilic scavenger, protects against mutagenesis in mouse skin treated in vivo with 2-(chloroethyl) ethyl sulfide, a mustard gas analog

    Energy Technology Data Exchange (ETDEWEB)

    Boulware, Stephen [Division of Pharmacy and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute, 1400 Barbara Jordan Blvd., Austin, TX 78723 (United States); Fields, Tammy; McIvor, Elizabeth; Powell, K. Leslie; Abel, Erika L. [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957 (United States); Vasquez, Karen M. [Division of Pharmacy and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute, 1400 Barbara Jordan Blvd., Austin, TX 78723 (United States); MacLeod, Michael C., E-mail: mcmacleod@mdanderson.org [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957 (United States)

    2012-09-01

    Sulfur mustard [bis(2-chloroethyl)sulfide, SM] is a well-known DNA-damaging agent that has been used in chemical warfare since World War I, and is a weapon that could potentially be used in a terrorist attack on a civilian population. Dermal exposure to high concentrations of SM produces severe, long-lasting burns. Topical exposure to high concentrations of 2-(chloroethyl) ethyl sulfide (CEES), a monofunctional analog of SM, also produces severe skin lesions in mice. Utilizing a genetically engineered mouse strain, Big Blue, that allows measurement of mutation frequencies in mouse tissues, we now show that topical treatment with much lower concentrations of CEES induces significant dose- and time-dependent increases in mutation frequency in mouse skin; the mutagenic exposures produce minimal toxicity as determined by standard histopathology and immunohistochemical analysis for cytokeratin 6 and the DNA-damage induced phosphorylation of histone H2AX (γ-H2AX). We attempted to develop a therapeutic that would inhibit the CEES-induced increase in mutation frequency in the skin. We observe that multi-dose, topical treatment with 2,6-dithiopurine (DTP), a known chemical scavenger of CEES, beginning 1 h post-exposure to CEES, completely abolishes the CEES-induced increase in mutation frequency. These findings suggest the possibility that DTP, previously shown to be non-toxic in mice, may be useful as a therapeutic agent in accidental or malicious human exposures to SM. -- Highlights: ► 200 mM 2-(chloroethyl) ethyl sulfide (CEES) induces mutations in mouse skin. ► This dose of CEES is not overtly toxic, as assayed by histopathology. ► 2,6-Dithiopurine (DTP), applied after CEES-treatment, abolishes CEES-mutagenesis. ► This supports the idea that sulfur mustards exhibit long biological half-lives.

  16. Assessment of the potential skin irritation of lysine-derivative anionic surfactants using mouse fibroblast and human keratinocytes as an alternative to animal testing

    OpenAIRE

    Sánchez Molina, Lourdes; Mitjans Arnal, Montserrat; Infante Martínez-Pardo, Ma. Rosa; Vinardell Martínez-Hidalgo, Ma. Pilar

    2004-01-01

    Purpose. The aim of this study was to identify new surfactants with low skin irritant properties for use in pharmaceutical and cosmetic formulations, employing cell culture as an alternative method to in vivo testing. In addition, we sought to establish whether potential cytotoxic properties were related to the size of the counterions bound to the surfactants. Methods. Cytotoxicity was assessed in the mouse fibroblast cell line 3T6, and the human keratinocyte cell line NCTC 2544, using the MT...

  17. Effects of type and amount of dietary fat on mouse skin tumor promotion.

    Science.gov (United States)

    Lo, H H; Locniskar, M F; Bechtel, D; Fischer, S M

    1994-01-01

    In a previous study (Cancer Res 51, 907, 1991) in which we found an inverse relationship between quantity of dietary corn oil and saturated fat, in a constant 15% fat diet, on the tumor promotion stage of skin carcinogenesis, it was not clear whether one or both types of fat played a modulatory role. The purpose of the present study therefore was to compare the effect of 1) increasing corn oil in corn oil-only diets and 2) increasing saturated fat, with a constant level of 5% corn oil, on tumor promotion. In the first study, the effects of five levels of dietary corn oil (5%, 10%, 15%, 20%, and 25%) on the incidence and rat of papilloma and carcinoma development were determined in female Sencar mice fed these diets one week after initiation with 7,12-dimethylbenz[a]anthracene and three weeks before the start of promotion with 12-O-tetradecanoylphorbol-13-acetate. A papilloma incidence of 100% was reached first in the 5% corn oil group, at 10 weeks, followed by the 10% group at 13 weeks and the 15% and 20% group at 16 weeks. The highest corn oil group achieved a 90% incidence. There were marked differences in latency of carcinoma development among the diet groups. At Week 29, the cumulative carcinoma incidence was 56% and 32%, respectively, in the 5% and 10% corn oil groups, whereas the incidence in the two highest corn oil (20% and 25%) groups was only 8% and 4%, respectively. In the second study, the effects of diets containing 5% corn oil and increasing levels of coconut oil (5%, 10%, 15%, and 20%) on the incidence and rat of papilloma and carcinoma development were determined, as described above. No significant difference in latency or incidence of papillomas or carcinomas was noted among these saturated fat diet groups. It thus appears that higher levels of dietary corn oil are associated with a reduced cancer incidence in this model system.

  18. The radiation effect on healing of surgical wound in mouse skin

    International Nuclear Information System (INIS)

    Remarkable improvement in control of malignant tumor was achieved by combined surgery and post-operative radiation therapy. In past, radiation therapy had been recommended after 4-6 weeks from operation because of worry about increased complication rate of surgical wound by post-operative irradiation. Nowadays, early surgical extirpation and early post-operative irradiation is recommended for better therapeutic effect. To evaluate the relationship between surgery-radiation interval and healing of surgical wound, an experimental study was undertaken using a total of 132 mice. A single dose of 2000 rads irradiation was delivered immediate after and on 1, 3, 5, 10, 14 days after incision and suture on the skin of hind limbs of mice. Tensile strengths of the wounds were measured after removal of stitches on 1st, 3rd, 5th, 7th, 10th, 14th and 21st post-operative days. The results are summarized as follows: 1. Wound healing was delayed by irradiation delivered within 3 days from operation. 2. No significant delay of wound healing was observed by irradiation on 5 or more days after operation. 3. Normal wound strength was attained at 21st post-operative day in any surgery-radiation interval. 4. More severe delay of wound healing by irradiation at 24 hrs after operation than by immediate post-operative irradiation although statistical significance is not confirmed. In conclusion, early post-operative irradiation delays healing of the surgical wound though ultimately tensile strength reaches the value of non-irradiated wound

  19. A brain-specific gene cluster isolated from the region of the mouse obesity locus is expressed in the adult hypothalamus and during mouse development

    Energy Technology Data Exchange (ETDEWEB)

    Laig-Webster, M.; Lim, M.E.; Chehab, F.F. [Univ. of California, San Francisco, CA (United States)

    1994-09-01

    The molecular defect underlying an autosomal recessive form of genetic obesity in a classical mouse model C57 BL/6J-ob/ob has not yet been elucidated. Whereas metabolic and physiological disturbances such as diabetes and hypertension are associated with obesity, the site of expression and the nature of the primary lesion responsible for this cascade of events remains elusive. Our efforts aimed at the positional cloning of the ob gene by YAC contig mapping and gene identification have resulted in the cloning of a brain-specific gene cluster from the ob critical region. The expression of this gene cluster is remarkably complex owing to the multitude of brain-specific mRNA transcripts detected on Northern blots. cDNA cloning of these transcripts suggests that they are expressed from different genes as well as by alternate splicing mechanisms. Furthermore, the genomic organization of the cluster appears to consist of at least two identical promoters displaying CpG islands characteristic of housekeeping genes, yet clearly involving tissue-specific expression. Sense and anti-sense synthetic RNA probes were derived from a common DNA sequence on 3 cDNA clones and hybridized to 8-16 days mouse embryonic stages and mouse adult brain sections. Expression in development was noticeable as of the 11th day of gestation and confined to the central nervous system mainly in the telencephalon and spinal cord. Coronal and sagittal sections of the adult mouse brain showed expression only in 3 different regions of the brain stem. In situ hybridization to mouse hypothalamus sections revealed the presence of a localized and specialized group of cells expressing high levels of mRNA, suggesting that this gene cluster may also be involved in the regulation of hypothalamic activities. The hypothalamus has long been hypothesized as a primary candidate tissue for the expression of the obesity gene mainly because of its well-established role in the regulation of energy metabolism and food intake.

  20. Skin regeneration in adult axolotls: a blueprint for scar-free healing in vertebrates.

    Directory of Open Access Journals (Sweden)

    Ashley W Seifert

    Full Text Available While considerable progress has been made towards understanding the complex processes and pathways that regulate human wound healing, regenerative medicine has been unable to develop therapies that coax the natural wound environment to heal scar-free. The inability to induce perfect skin regeneration stems partly from our limited understanding of how scar-free healing occurs in a natural setting. Here we have investigated the wound repair process in adult axolotls and demonstrate that they are capable of perfectly repairing full thickness excisional wounds made on the flank. In the context of mammalian wound repair, our findings reveal a substantial reduction in hemostasis, reduced neutrophil infiltration and a relatively long delay in production of new extracellular matrix (ECM during scar-free healing. Additionally, we test the hypothesis that metamorphosis leads to scarring and instead show that terrestrial axolotls also heal scar-free, albeit at a slower rate. Analysis of newly forming dermal ECM suggests that low levels of fibronectin and high levels of tenascin-C promote regeneration in lieu of scarring. Lastly, a genetic analysis during wound healing comparing epidermis between aquatic and terrestrial axolotls suggests that matrix metalloproteinases may regulate the fibrotic response. Our findings outline a blueprint to understand the cellular and molecular mechanisms coordinating scar-free healing that will be useful towards elucidating new regenerative therapies targeting fibrosis and wound repair.

  1. Establishment of a tamoxifen-inducible Cre-driver mouse strain for widespread and temporal genetic modification in adult mice.

    Science.gov (United States)

    Ichise, Hirotake; Hori, Akiko; Shiozawa, Seiji; Kondo, Saki; Kanegae, Yumi; Saito, Izumu; Ichise, Taeko; Yoshida, Nobuaki

    2016-07-29

    Temporal genetic modification of mice using the ligand-inducible Cre/loxP system is an important technique that allows the bypass of embryonic lethal phenotypes and access to adult phenotypes. In this study, we generated a tamoxifen-inducible Cre-driver mouse strain for the purpose of widespread and temporal Cre recombination. The new line, named CM32, expresses the GFPneo-fusion gene in a wide variety of tissues before FLP recombination and tamoxifen-inducible Cre after FLP recombination. Using FLP-recombined CM32 mice (CM32Δ mice) and Cre reporter mouse lines, we evaluated the efficiency of Cre recombination with and without tamoxifen administration to adult mice, and found tamoxifen-dependent induction of Cre recombination in a variety of adult tissues. In addition, we demonstrated that conditional activation of an oncogene could be achieved in adults using CM32Δ mice. CM32Δ;T26 mice, which harbored a Cre recombination-driven, SV40 large T antigen-expressing transgene, were viable and fertile. No overt phenotype was found in the mice up to 3 months after birth. Although they displayed pineoblastomas (pinealoblastomas) and/or thymic enlargement due to background Cre recombination by 6 months after birth, they developed epidermal hyperplasia when administered tamoxifen. Collectively, our results suggest that the CM32Δ transgenic mouse line can be applied to the assessment of adult phenotypes in mice with loxP-flanked transgenes. PMID:26923756

  2. Growth Factors Released from Gelatin Hydrogel Microspheres Increase New Neurons in the Adult Mouse Brain

    Directory of Open Access Journals (Sweden)

    Kanako Nakaguchi

    2012-01-01

    Full Text Available Recent studies have shown that new neurons are continuously generated by endogenous neural stem cells in the subventricular zone (SVZ of the adult mammalian brain. Some of these new neurons migrate to injured brain tissues and differentiate into mature neurons, suggesting that such new neurons may be able to replace neurons lost to degenerative disease or injury and improve or repair neurological deficits. Here, we tested whether delivering growth factors via gelatin hydrogel microspheres would support neurogenesis in the SVZ. Insulin-like growth factor-1 (IGF-1-containing microspheres increased the number of new neurons in the SVZ. Hepatocyte growth factor (HGF-containing microspheres increased the number of new neurons migrating from the SVZ towards the injured striatum in a stroke model in mouse. These results suggest that the strategy of using gelatin hydrogel microspheres to achieve the sustained release of growth factors holds promise for the clinical regeneration of damaged brain tissues from endogenous neural stem cells in the adult SVZ.

  3. Temporal aspects of tumorigenic response to individual and mixed carcinogens. Comprehensive progress report, June 1, 1975--May 31, 1978. [Mouse skin, rats, hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Albert, R.E.; Burns, F.J.; Altshuler, B.

    1978-02-01

    The research proposed here is designed to obtain a better understanding of the temporal kinetics of tumor induction when one or more carcinogens are present simultaneously or sequentially for prolonged periods of time. Studies done to date under this contract have shown that carcinogenesis in mouse skin by polycyclic aromatic hydrocarbon carcinogens is consistent with the induction of dependent and autonomous cell transformations by the carcinogen followed by the conversion of autonomous tumor cells into malignancies at a rate which is determined by the level of carcinogen exposure. Dependent cell transformations remain latent in the skin unless expressed by a promoting agent. Dependent neoplasia appears to follow one-hit kinetics while malignancy is a multihit endpoint. Dose-related and time-related aspects of tumor induction are separable in the initiation-promotion system of mouse skin which along with rat skin and hamster lung is being used as a model for testing hypotheses. Results to date provide the basis for a new interpretation of the linear non-threshold extrapolation model. The broad aim of the study is to provide a basis or rationale for estimating risks associated with prolonged exposures to carcinogens found in the environment and to predict how different tissues and species respond to the same carcinogens.

  4. Temporal profiles of synaptic plasticity-related signals in adult mouse hippocampus with methotrexate treatment

    Institute of Scientific and Technical Information of China (English)

    Miyoung Yang; Juhwan Kim; Sung-Ho Kim; Joong-Sun Kim; Taekyun Shin; Changjong Moon

    2012-01-01

    Methotrexate, which is used to treat many malignancies and autoimmune diseases, affects brain functions including hippocampal-dependent memory function. However, the precise mechanisms underlying methotrexate-induced hippocampal dysfunction are poorly understood. To evaluate temporal changes in synaptic plasticity-related signals, the expression and activity of N-methyl-D-aspartic acid receptor 1, calcium/calmodulin-dependent protein kinase II, extracellular signal-regulated kinase 1/2, cAMP responsive element-binding protein, glutamate receptor 1, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor were examined in the hippocampi of adult C57BL/6 mice after methotrexate (40 mg/kg) intraperitoneal injection. Western blot analysis showed biphasic changes in synaptic plasticity-related signals in adult hippocampi following methotrexate treatment. N-methyl-D-aspartic acid receptor 1, cal-cium/calmodulin-dependent protein kinase II, and glutamate receptor 1 were acutely activated dur-ing the early phase (1 day post-injection), while extracellular signal-regulated kinase 1/2 and cAMP responsive element-binding protein activation showed biphasic increases during the early (1 day post-injection) and late phases (7-14 days post-injection). Brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression increased significantly during the late phase (7-14 days post-injection). Therefore, methotrexate treatment affects synaptic plasticity-related signals in the adult mouse hippocampus, suggesting that changes in synaptic plasticity-related signals may be associated with neuronal survival and plasticity-related cellular remodeling.

  5. Stroke increases neural stem cells and angiogenesis in the neurogenic niche of the adult mouse.

    Directory of Open Access Journals (Sweden)

    Rui Lan Zhang

    Full Text Available The unique cellular and vascular architecture of the adult ventricular-subventricular zone (V/SVZ neurogenic niche plays an important role in regulating neural stem cell function. However, the in vivo identification of neural stem cells and their relationship to blood vessels within this niche in response to stroke remain largely unknown. Using whole-mount preparation of the lateral ventricle wall, we examined the architecture of neural stem cells and blood vessels in the V/SVZ of adult mouse over the course of 3 months after onset of focal cerebral ischemia. Stroke substantially increased the number of glial fibrillary acidic protein (GFAP positive neural stem cells that are in contact with the cerebrospinal fluid (CSF via their apical processes at the center of pinwheel structures formed by ependymal cells residing in the lateral ventricle. Long basal processes of these cells extended to blood vessels beneath the ependymal layer. Moreover, stroke increased V/SVZ endothelial cell proliferation from 2% in non-ischemic mice to 12 and 15% at 7 and 14 days after stroke, respectively. Vascular volume in the V/SVZ was augmented from 3% of the total volume prior to stroke to 6% at 90 days after stroke. Stroke-increased angiogenesis was closely associated with neuroblasts that expanded to nearly encompass the entire lateral ventricular wall in the V/SVZ. These data indicate that stroke induces long-term alterations of the neural stem cell and vascular architecture of the adult V/SVZ neurogenic niche. These post-stroke structural changes may provide insight into neural stem cell mediation of stroke-induced neurogenesis through the interaction of neural stem cells with proteins in the CSF and their sub-ependymal neurovascular interaction.

  6. Multipotent stem cells isolated from the adult mouse retina are capable of producing functional photoreceptor cells

    Institute of Scientific and Technical Information of China (English)

    Tianqing Li; Michelle Lewallen; Shuyi Chen; Wei Yu; Nian Zhang; Ting Xie

    2013-01-01

    Various stem cell types have been tested for their potential application in treating photoreceptor degenerative diseases,such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD).Only embryonic stem cells (ESCs) have so far been shown to generate functional photoreceptor cells restoring light response of photoreceptordeficient mice,but there is still some concern of tumor formation.In this study,we have successfully cultured Nestin+Sox2+Pax6+ multipotent retinal stem cells (RSCs) from the adult mouse retina,which are capable of producing functional photoreceptor cells that restore the light response of photoreceptor-deficient rd1 mutant mice following transplantation.After they have been expanded for over 35 passages in the presence of FGF and EGF,the cultured RSCs still maintain stable proliferation and differentiation potential.Under proper differentiation conditions,they can differentiate into all the major retinal cell types found in the adult retina.More importantly,they can efficiently differentiate into photoreceptor cells under optimized differentiation conditions.Following transplantation into the subretinal space of slowly degenerating rd7 mutant eyes,RSC-derived photoreceptor cells integrate into the retina,morphologically resembling endogenous photoreceptors and forming synapases with resident retinal neurons.When transplanted into eyes of photoreceptor-deficient rd1 mutant mice,a RP model,RSC-derived photoreceptors can partially restore light response,indicating that those RSC-derived photoreceptors are functional.Finally,there is no evidence for tumor formation in the photoreceptor-transplanted eyes.Therefore,this study has demonstrated that RSCs isolated from the adult retina have the potential of producing functional photoreceptor cells that can potentially restore lost vision caused by loss of photoreceptor cells in RP and AMD.

  7. Hyaluronan and Fibrin Biomaterial as Scaffolds for Neuronal Differentiation of Adult Stem Cells Derived from Adipose Tissue and Skin

    Directory of Open Access Journals (Sweden)

    Chiara Gardin

    2011-10-01

    Full Text Available Recently, we have described a simple protocol to obtain an enriched culture of adult stem cells organized in neurospheres from two post-natal tissues: skin and adipose tissue. Due to their possible application in neuronal tissue regeneration, here we tested two kinds of scaffold well known in tissue engineering application: hyaluronan based membranes and fibrin-glue meshes. Neurospheres from skin and adipose tissue were seeded onto two scaffold types: hyaluronan based membrane and fibrin-glue meshes. Neurospheres were then induced to acquire a glial and neuronal-like phenotype. Gene expression, morphological feature and chromosomal imbalance (kariotype were analyzed and compared. Adipose and skin derived neurospheres are able to grow well and to differentiate into glial/neuron cells without any chromosomal imbalance in both scaffolds. Adult cells are able to express typical cell surface markers such as S100; GFAP; nestin; βIII tubulin; CNPase. In summary, we have demonstrated that neurospheres isolated from skin and adipose tissues are able to differentiate in glial/neuron-like cells, without any chromosomal imbalance in two scaffold types, useful for tissue engineering application: hyaluronan based membrane and fibrin-glue meshes.

  8. A comparative study of baby immature and adult shoots of Aloe vera on UVB-induced skin photoaging in vitro.

    Science.gov (United States)

    Hwang, Eunson; Kim, Su Hyeon; Lee, Sarah; Lee, Choong Hwan; Do, Seon-Gil; Kim, Jinwan; Kim, Sun Yeou

    2013-12-01

    Ultraviolet (UV) irradiation induces photo-damage of the skin, which in turn causes depletion of the dermal extracellular matrix and chronic alterations in skin structure. Skin wrinkle formations are associated with collagen synthesis and matrix metalloproteinase (MMP) expression. The production of type I procollagen is regulated by transforming growth factor-β1 (TGF-β1) expression; the activation of MMP is also correlated with an increase of interleukin-6 (IL-6). Aloe barbadensis M. (Aloe vera) is widely used in cosmetic and pharmaceutical products. In this study, we examined whether baby aloe shoot extract (BAE, immature aloe extract), which is from the one-month-old shoots of Aloe vera, and adult aloe shoot extract (AE), which is from the four-month-old shoots of Aloe vera, have a protective effect on UVB-induced skin photoaging in normal human dermal fibroblasts (NHDFs). The effects of BAE and AE on UVB-induced photoaging were tested by measuring the levels of reactive oxygen species, MMP-1, MMP-3, IL-6, type I procollagen, and TGF-β1 after UVB irradiation. We found that NHDF cells treated with BAE after UVB-irradiation suppressed MMP-1, MMP-3, and IL-6 levels compared to the AE-treated cells. Furthermore, BAE treatment elevated type I procollagen and TGF-β1 levels. Our results suggest that BAE may potentially protect the skin from UVB-induced damage more than AE.

  9. Anoctamins support calcium-dependent chloride secretion by facilitating calcium signaling in adult mouse intestine.

    Science.gov (United States)

    Schreiber, Rainer; Faria, Diana; Skryabin, Boris V; Wanitchakool, Podchanart; Rock, Jason R; Kunzelmann, Karl

    2015-06-01

    Intestinal epithelial electrolyte secretion is activated by increase in intracellular cAMP or Ca(2+) and opening of apical Cl(-) channels. In infants and young animals, but not in adults, Ca(2+)-activated chloride channels may cause secretory diarrhea during rotavirus infection. While detailed knowledge exists concerning the contribution of cAMP-activated cystic fibrosis transmembrane conductance regulator (CFTR) channels, analysis of the role of Ca(2+)-dependent Cl(-) channels became possible through identification of the anoctamin (TMEM16) family of proteins. We demonstrate expression of several anoctamin paralogues in mouse small and large intestines. Using intestinal-specific mouse knockout models for anoctamin 1 (Ano1) and anoctamin 10 (Ano10) and a conventional knockout model for anoctamin 6 (Ano6), we demonstrate the role of anoctamins for Ca(2+)-dependent Cl(-) secretion induced by the muscarinic agonist carbachol (CCH). Ano1 is preferentially expressed in the ileum and large intestine, where it supports Ca(2+)-activated Cl(-) secretion. In contrast, Ano10 is essential for Ca(2+)-dependent Cl(-) secretion in jejunum, where expression of Ano1 was not detected. Although broadly expressed, Ano6 has no role in intestinal cholinergic Cl(-) secretion. Ano1 is located in a basolateral compartment/membrane rather than in the apical membrane, where it supports CCH-induced Ca(2+) increase, while the essential and possibly only apical Cl(-) channel is CFTR. These results define a new role of Ano1 for intestinal Ca(2+)-dependent Cl(-) secretion and demonstrate for the first time a contribution of Ano10 to intestinal transport.

  10. Vasoactive intestinal peptide antagonist treatment during mouse embryogenesis impairs social behavior and cognitive function of adult male offspring.

    Science.gov (United States)

    Hill, Joanna M; Cuasay, Katrina; Abebe, Daniel T

    2007-07-01

    Vasoactive intestinal peptide (VIP) is a regulator of rodent embryogenesis during the period of neural tube closure. VIP enhanced growth in whole cultured mouse embryos; treatment with a VIP antagonist during embryogenesis inhibited growth and development. VIP antagonist treatment during embryogenesis also had permanent effects on adult brain chemistry and impaired social recognition behavior in adult male mice. The neurological deficits of autism appear to be initiated during neural tube closure and social behavior deficits are among the key characteristics of this disorder that is more common in males and is frequently accompanied by mental retardation. The current study examined the blockage of VIP during embryogenesis as a model for the behavioral deficits of autism. Treatment of pregnant mice with a VIP antagonist during embryonic days 8 through 10 had no apparent effect on the general health or sensory or motor capabilities of adult offspring. However, male offspring exhibited reduced sociability in the social approach task and deficits in cognitive function, as assessed through cued and contextual fear conditioning. Female offspring did not show these deficiencies. These results suggest that this paradigm has usefulness as a mouse model for aspects of autism as it selectively impairs male offspring who exhibit the reduced social behavior and cognitive dysfunction seen in autism. Furthermore, the study indicates that the foundations of some aspects of social behavior are laid down early in mouse embryogenesis, are regulated in a sex specific manner and that interference with embryonic regulators such as VIP can have permanent effects on adult social behavior.

  11. Transplantation of adult mouse iPS cell-derived photoreceptor precursors restores retinal structure and function in degenerative mice.

    Directory of Open Access Journals (Sweden)

    Budd A Tucker

    Full Text Available This study was designed to determine whether adult mouse induced pluripotent stem cells (iPSCs, could be used to produce retinal precursors and subsequently photoreceptor cells for retinal transplantation to restore retinal function in degenerative hosts. iPSCs were generated using adult dsRed mouse dermal fibroblasts via retroviral induction of the transcription factors Oct4, Sox2, KLF4 and c-Myc. As with normal mouse ES cells, adult dsRed iPSCs expressed the pluripotency genes SSEA1, Oct4, Sox2, KLF4, c-Myc and Nanog. Following transplantation into the eye of immune-compromised retinal degenerative mice these cells proceeded to form teratomas containing tissue comprising all three germ layers. At 33 days post-differentiation a large proportion of the cells expressed the retinal progenitor cell marker Pax6 and went on to express the photoreceptor markers, CRX, recoverin, and rhodopsin. When tested using calcium imaging these cells were shown to exhibit characteristics of normal retinal physiology, responding to delivery of neurotransmitters. Following subretinal transplantation into degenerative hosts differentiated iPSCs took up residence in the retinal outer nuclear layer and gave rise to increased electro retinal function as determined by ERG and functional anatomy. As such, adult fibroblast-derived iPSCs provide a viable source for the production of retinal precursors to be used for transplantation and treatment of retinal degenerative disease.

  12. Prevalence and heritability of skin picking in an adult community sample: a twin study.

    Science.gov (United States)

    Monzani, Benedetta; Rijsdijk, Fruhling; Cherkas, Lynn; Harris, Juliette; Keuthen, Nancy; Mataix-Cols, David

    2012-07-01

    Skin-picking disorder (SPD) is a disabling psychiatric condition that can lead to skin damage and other medical complications. Epidemiological data is scarce and its causes are unknown. The present study examined the prevalence and heritability of skin-picking symptoms in a large sample of twins. A total of 2,518 twins completed a valid and reliable self-report measure of skin-picking behavior. The prevalence of clinically significant skin picking was established using empirically derived cut-offs. Twin modeling methods were employed to decompose the variance in the liability to skin picking into additive genetic and shared and non-shared environmental factors. A total of 1.2% of twins scored above the cut-off, indicative of clinically significant skin picking. All these participants were women. Univariate model-fitting analyses (female twins only, N = 2,191) showed that genetic factors accounted for approximately 40% (95% CI 19-58%) of the variance in skin picking, with non-shared environmental factors and measurement error accounting for the remaining variance (60% [95% CI 42-81%]). Shared environmental factors were negligible. It is concluded that pathological skin picking is relatively prevalent problem, particularly among women, and that it tends to run in families primarily due to genetic factors. Non-shared environmental factors are also likely to play an important role in its etiology. PMID:22619132

  13. Rho kinase inhibitor y-27632 prolongs the life span of adult human keratinocytes, enhances skin equivalent development, and facilitates lentiviral transduction.

    NARCIS (Netherlands)

    Bogaard, E.H.J. van den; Rodijk-Olthuis, D.; Jansen, P.A.M.; Vlijmen-Willems, I.M.J.J. van; Erp, P.E.J. van; Joosten, I.; Zeeuwen, P.L.J.M.; Schalkwijk, J.

    2012-01-01

    The use of tissue-engineered human skin equivalents (HSE) for fundamental research and industrial application requires the expansion of keratinocytes from a limited number of skin biopsies donated by adult healthy volunteers or patients. A pharmacological inhibitor of Rho-associated protein kinases,

  14. Effect of topical application of antioxidants and free radical scavengers on protection of hairless mouse skin exposed to chronic doses of ultraviolet B

    International Nuclear Information System (INIS)

    treatment, respectively. Conclusion: Data from these studies suggest that low level chronic exposures to UV can lead to alteration of the skin, like epidermal thickening and appearance of sunburn cells. The data also indicates that a mix of common antioxidants and free radical scavengers are photoprotective against chronic skin damage in the hairless mouse skin model. (au)

  15. Effect of topical application of antioxidants and free radical scavengers on protection of hairless mouse skin exposed to chronic doses of ultraviolet B

    Energy Technology Data Exchange (ETDEWEB)

    Muizzuddin, N.; Shakoori, A.R. [Univ. of the Punjab, Dept. of Zoology, Cell and Molecular Biology Lab., Lahore (Pakistan); Marenus, K.D. [SUNY at Stonybrook, Stonybrook, NY (United States)

    1998-11-01

    treatment, respectively. Conclusion: Data from these studies suggest that low level chronic exposures to UV can lead to alteration of the skin, like epidermal thickening and appearance of sunburn cells. The data also indicates that a mix of common antioxidants and free radical scavengers are photoprotective against chronic skin damage in the hairless mouse skin model. (au)

  16. Photosensitivity of murine skin greatly depends on the genetic background: clinically relevant dose as a new measure to replace minimal erythema dose in mouse studies.

    Science.gov (United States)

    Gyöngyösi, Nóra; Lőrincz, Kende; Keszeg, András; Haluszka, Dóra; Bánvölgyi, András; Tátrai, Erika; Kárpáti, Sarolta; Wikonkál, Norbert M

    2016-07-01

    Artificial UV irradiation of murine skin is a frequently used method for testing photosensitivity, study carcinogenesis and photoprotective effects of different compounds. However, doses of UV radiation and mouse strains used in experiments vary greatly. The genetic background of mice may influence the photosensitivity as melanin content, pigmentation and hair cycle parameters are dissimilar. Doses of UV are often expressed in relation to the minimal erythema dose (MED) that was not necessarily determined for the given strain. We set out to standardize the method of measuring photosensitivity in three commonly used mouse strains, C57BL/6N, Balb/c and SKH-1. We found that MED may not be determined for some strains as erythema development in mice with diverse genotypes differs greatly. We measured the oedema response in vivo and ex vivo by using OCT. Given the strain-specific variability of erythema, we introduced Clinically Relevant Dose (CRD) as a new term to replace MED in experiments, to describe the lowest dose that triggers a perceptible skin reaction in mice. Not only the CRD but the proportion of erythema and oedema were different in strains examined. C57BL/6N mice display skin reactions at the lowest UVB dose, while SKH-1 hairless mice show changes, mostly oedema, after higher doses of UVB. The cellular composition and skin thickness were examined by histopathology. IL-1beta and IL-6 levels in skin correlated with the increasing doses of UVB. Despite the variations in the degree of erythema and oedema, no major differences in cytokine expressions were seen among various strains of mice. PMID:26910301

  17. Peristomal moisture-associated skin damage in adults with fecal ostomies: a comprehensive review and consensus.

    Science.gov (United States)

    Gray, Mikel; Colwell, Janice C; Doughty, Dorothy; Goldberg, Margaret; Hoeflok, Jo; Manson, Andrea; McNichol, Laurie; Rao, Samara

    2013-01-01

    Approximately 1 million persons living in North America have an ostomy, and approximately 70% will experience stomal or peristomal complications. The most prevalent of these complications is peristomal skin damage, and the most common form of peristomal skin damage occurs when the skin is exposed to effluent from the ostomy, resulting in inflammation and erosion of the skin. Despite its prevalence, research-based evidence related to the assessment, prevention, and management of peristomal moisture-associated skin damage is sparse, and current practice is largely based on expert opinion. In order to address current gaps in clinical evidence and knowledge of this condition, a group of WOC and enterostomal therapy nurses with expertise in ostomy care was convened in 2012. This article summarizes results from the panel's literature review and summarizes consensus-based statements outlining best practices for the assessment, prevention, and management of peristomal moisture-associated dermatitis among patients with fecal ostomies.

  18. The circadian clock in skin: implications for adult stem cells, tissue regeneration, cancer, aging, and immunity.

    Science.gov (United States)

    Plikus, Maksim V; Van Spyk, Elyse N; Pham, Kim; Geyfman, Mikhail; Kumar, Vivek; Takahashi, Joseph S; Andersen, Bogi

    2015-06-01

    Historically, work on peripheral circadian clocks has been focused on organs and tissues that have prominent metabolic functions, such as the liver, fat, and muscle. In recent years, skin has emerged as a model for studying circadian clock regulation of cell proliferation, stem cell functions, tissue regeneration, aging, and carcinogenesis. Morphologically, skin is complex, containing multiple cell types and structures, and there is evidence for a functional circadian clock in most, if not all, of its cell types. Despite the complexity, skin stem cell populations are well defined, experimentally tractable, and exhibit prominent daily cell proliferation cycles. Hair follicle stem cells also participate in recurrent, long-lasting cycles of regeneration: the hair growth cycles. Among other advantages of skin is a broad repertoire of available genetic tools enabling the creation of cell type-specific circadian mutants. Also, due to the accessibility of skin, in vivo imaging techniques can be readily applied to study the circadian clock and its outputs in real time, even at the single-cell level. Skin provides the first line of defense against many environmental and stress factors that exhibit dramatic diurnal variations such as solar ultraviolet (UV) radiation and temperature. Studies have already linked the circadian clock to the control of UVB-induced DNA damage and skin cancers. Due to the important role that skin plays in the defense against microorganisms, it also represents a promising model system to further explore the role of the clock in the regulation of the body's immune functions. To that end, recent studies have already linked the circadian clock to psoriasis, one of the most common immune-mediated skin disorders. Skin also provides opportunities to interrogate the clock regulation of tissue metabolism in the context of stem cells and regeneration. Furthermore, many animal species feature prominent seasonal hair molt cycles, offering an attractive model

  19. Ex vivo infection of human embryonic spinal cord neurons prior to transplantation into adult mouse cord

    Directory of Open Access Journals (Sweden)

    Dénes Ádám

    2010-05-01

    Full Text Available Abstract Background Genetically modified pseudorabies virus (Prv proved suitable for the delivery of foreign genes to rodent embryonic neurons ex vivo and maintaining foreign gene expression after transplantation into spinal cord in our earlier study. The question arose of whether human embryonic neurons, which are known to be more resistant to Prv, could also be infected with a mutant Prv. Specifically, we investigated whether a mutant Prv with deleted ribonucleotide reductase and early protein 0 genes has the potential to deliver marker genes (gfp and β-gal into human embryonic spinal cord neurons and whether the infected neurons maintain expression after transplantation into adult mouse cord. Results The results revealed that the mutant Prv effectively infected human embryonic spinal cord neurons ex vivo and the grafted cells exhibited reporter gene expression for several weeks. Grafting of infected human embryonic cells into the spinal cord of immunodeficient (rnu-/rnu- mice resulted in the infection of some of the host neurons. Discussion These results suggest that Prv is suitable for the delivery of foreign genes into transplantable human cells. This delivery method may offer a new approach to use genetically modified cells for grafting in animal models where spinal cord neuronal loss or axon degeneration occurs.

  20. Neurotoxic effects of ochratoxin A on the subventricular zone of adult mouse brain.

    Science.gov (United States)

    Paradells, Sara; Rocamonde, Brenda; Llinares, Cristina; Herranz-Pérez, Vicente; Jimenez, Misericordia; Garcia-Verdugo, Jose Manuel; Zipancic, Ivan; Soria, Jose Miguel; Garcia-Esparza, Ma Angeles

    2015-07-01

    Ochratoxin A (OTA), a mycotoxin that was discovered as a secondary metabolite of the fungal species Aspergillus and Penicillium, is a common contaminant in food and animal feed. This mycotoxin has been described as teratogenic, carcinogenic, genotoxic, immunotoxic and has been proven a potent neurotoxin. Other authors have previously reported the effects of OTA in different structures of the central nervous system as well as in some neurogenic regions. However, the impact of OTA exposure in the subventricular zone (SVZ) has not been assessed yet. To elucidate whether OTA affects neural precursors of the mouse SVZ we investigated, in vitro and in vivo, the effects of OTA exposure on the SVZ and on the neural precursors obtained from this neurogenic niche. In this work, we prove the cumulative effect of OTA exposure on proliferation, differentiation and depletion of neural stem cells cultured from the SVZ. In addition, we corroborated these results in vivo by immunohistochemistry and electron microscopy. As a result, we found a significant alteration in the proliferation process, which was evidenced by a decrease in the number of 5-bromo-2-deoxyuridine-positive cells and glial cells, as well as, a significant decrease in the number of neuroblasts in the SVZ. To summarize, in this study we demonstrate how OTA could be a threat to the developing and the adult SVZ through its impact in cell viability, proliferation and differentiation in a dose-dependent manner.

  1. Adult pallium transcriptomes surprise in not reflecting predicted homologies across diverse chicken and mouse pallial sectors.

    Science.gov (United States)

    Belgard, T Grant; Montiel, Juan F; Wang, Wei Zhi; García-Moreno, Fernando; Margulies, Elliott H; Ponting, Chris P; Molnár, Zoltán

    2013-08-01

    The thorniest problem in comparative neurobiology is the identification of the particular brain region of birds and reptiles that corresponds to the mammalian neocortex [Butler AB, Reiner A, Karten HJ (2011) Ann N Y Acad Sci 1225:14-27; Wang Y, Brzozowska-Prechtl A, Karten HJ (2010) Proc Natl Acad Sci USA 107(28):12676-12681]. We explored which genes are actively transcribed in the regions of controversial ancestry in a representative bird (chicken) and mammal (mouse) at adult stages. We conducted four analyses comparing the expression patterns of their 5,130 most highly expressed one-to-one orthologous genes that considered global patterns of expression specificity, strong gene markers, and coexpression networks. Our study demonstrates transcriptomic divergence, plausible convergence, and, in two exceptional cases, conservation between specialized avian and mammalian telencephalic regions. This large-scale study potentially resolves the complex relationship between developmental homology and functional characteristics on the molecular level and settles long-standing evolutionary debates.

  2. Neurotoxic effects of ochratoxin A on the subventricular zone of adult mouse brain.

    Science.gov (United States)

    Paradells, Sara; Rocamonde, Brenda; Llinares, Cristina; Herranz-Pérez, Vicente; Jimenez, Misericordia; Garcia-Verdugo, Jose Manuel; Zipancic, Ivan; Soria, Jose Miguel; Garcia-Esparza, Ma Angeles

    2015-07-01

    Ochratoxin A (OTA), a mycotoxin that was discovered as a secondary metabolite of the fungal species Aspergillus and Penicillium, is a common contaminant in food and animal feed. This mycotoxin has been described as teratogenic, carcinogenic, genotoxic, immunotoxic and has been proven a potent neurotoxin. Other authors have previously reported the effects of OTA in different structures of the central nervous system as well as in some neurogenic regions. However, the impact of OTA exposure in the subventricular zone (SVZ) has not been assessed yet. To elucidate whether OTA affects neural precursors of the mouse SVZ we investigated, in vitro and in vivo, the effects of OTA exposure on the SVZ and on the neural precursors obtained from this neurogenic niche. In this work, we prove the cumulative effect of OTA exposure on proliferation, differentiation and depletion of neural stem cells cultured from the SVZ. In addition, we corroborated these results in vivo by immunohistochemistry and electron microscopy. As a result, we found a significant alteration in the proliferation process, which was evidenced by a decrease in the number of 5-bromo-2-deoxyuridine-positive cells and glial cells, as well as, a significant decrease in the number of neuroblasts in the SVZ. To summarize, in this study we demonstrate how OTA could be a threat to the developing and the adult SVZ through its impact in cell viability, proliferation and differentiation in a dose-dependent manner. PMID:25256750

  3. Time-lapse imaging of neuroblast migration in acute slices of the adult mouse forebrain.

    Science.gov (United States)

    Khlghatyan, Jivan; Saghatelyan, Armen

    2012-01-01

    the stationary and migratory phases is crucial for the unambiguous interpretation of results. We also performed multiple z-step acquisitions to monitor neuroblasts migration in 3D. Wide-field fluorescent imaging has been used extensively to visualize neuronal migration. Here, we describe detailed protocol for labeling neuroblasts, performing real-time video-imaging of neuroblast migration in acute slices of the adult mouse forebrain, and analyzing cell migration. While the described protocol exemplified the migration of neuroblasts in the adult RMS, it can also be used to follow cell migration in embryonic and early postnatal brains. PMID:23007608

  4. PAX6 MiniPromoters drive restricted expression from rAAV in the adult mouse retina.

    Science.gov (United States)

    Hickmott, Jack W; Chen, Chih-Yu; Arenillas, David J; Korecki, Andrea J; Lam, Siu Ling; Molday, Laurie L; Bonaguro, Russell J; Zhou, Michelle; Chou, Alice Y; Mathelier, Anthony; Boye, Sanford L; Hauswirth, William W; Molday, Robert S; Wasserman, Wyeth W; Simpson, Elizabeth M

    2016-01-01

    Current gene therapies predominantly use small, strong, and readily available ubiquitous promoters. However, as the field matures, the availability of small, cell-specific promoters would be greatly beneficial. Here we design seven small promoters from the human paired box 6 (PAX6) gene and test them in the adult mouse retina using recombinant adeno-associated virus. We chose the retina due to previous successes in gene therapy for blindness, and the PAX6 gene since it is: well studied; known to be driven by discrete regulatory regions; expressed in therapeutically interesting retinal cell types; and mutated in the vision-loss disorder aniridia, which is in need of improved therapy. At the PAX6 locus, 31 regulatory regions were bioinformatically predicted, and nine regulatory regions were constructed into seven MiniPromoters. Driving Emerald GFP, these MiniPromoters were packaged into recombinant adeno-associated virus, and injected intravitreally into postnatal day 14 mice. Four MiniPromoters drove consistent retinal expression in the adult mouse, driving expression in combinations of cell-types that endogenously express Pax6: ganglion, amacrine, horizontal, and Müller glia. Two PAX6-MiniPromoters drive expression in three of the four cell types that express PAX6 in the adult mouse retina. Combined, they capture all four cell types, making them potential tools for research, and PAX6-gene therapy for aniridia. PMID:27556059

  5. PAX6 MiniPromoters drive restricted expression from rAAV in the adult mouse retina

    Science.gov (United States)

    Hickmott, Jack W; Chen, Chih-yu; Arenillas, David J; Korecki, Andrea J; Lam, Siu Ling; Molday, Laurie L; Bonaguro, Russell J; Zhou, Michelle; Chou, Alice Y; Mathelier, Anthony; Boye, Sanford L; Hauswirth, William W; Molday, Robert S; Wasserman, Wyeth W; Simpson, Elizabeth M

    2016-01-01

    Current gene therapies predominantly use small, strong, and readily available ubiquitous promoters. However, as the field matures, the availability of small, cell-specific promoters would be greatly beneficial. Here we design seven small promoters from the human paired box 6 (PAX6) gene and test them in the adult mouse retina using recombinant adeno-associated virus. We chose the retina due to previous successes in gene therapy for blindness, and the PAX6 gene since it is: well studied; known to be driven by discrete regulatory regions; expressed in therapeutically interesting retinal cell types; and mutated in the vision-loss disorder aniridia, which is in need of improved therapy. At the PAX6 locus, 31 regulatory regions were bioinformatically predicted, and nine regulatory regions were constructed into seven MiniPromoters. Driving Emerald GFP, these MiniPromoters were packaged into recombinant adeno-associated virus, and injected intravitreally into postnatal day 14 mice. Four MiniPromoters drove consistent retinal expression in the adult mouse, driving expression in combinations of cell-types that endogenously express Pax6: ganglion, amacrine, horizontal, and Müller glia. Two PAX6-MiniPromoters drive expression in three of the four cell types that express PAX6 in the adult mouse retina. Combined, they capture all four cell types, making them potential tools for research, and PAX6-gene therapy for aniridia. PMID:27556059

  6. Odorous and non-fatal skin secretion of adult wrinkled frog (Rana rugosa is effective in avoiding predation by snakes.

    Directory of Open Access Journals (Sweden)

    Yuri Yoshimura

    Full Text Available The roles played by nonfatal secretions of adult anurans in the avoidance of predation remain unknown. The adult Wrinkled frog (Rana rugosa has warty skin with the odorous mucus secretion that is not fatal to the snake Elaphe quadrivirgata. We fed R. rugosa or Fejervarya limnocharis, which resembles R. rugosa in appearance and has mucus secretion, to snakes and compared the snakes' responses to the frogs. Compared to F. limnocharis, R. rugosa was less frequently bitten or swallowed by snakes. The snakes that bit R. rugosa spat out the frogs and showed mouth opening (gaping behavior, while the snakes that bit F. limnocharis did not show gaping behavior. We also compared the responses of the snakes to R. rugosa and F. limnocharis secretions. We coated palatable R. japonica with secretions from R. rugosa or F. limnocharis. The frogs coated by R. rugosa secretion were less frequently bitten or swallowed than those coated by F. limnocharis secretion. We concluded that compared to different frog species of similar sizes, the adult R. rugosa was less frequently preyed upon by, and that its skin secretion was effective in avoiding predation by snakes.

  7. Odorous and non-fatal skin secretion of adult wrinkled frog (Rana rugosa) is effective in avoiding predation by snakes.

    Science.gov (United States)

    Yoshimura, Yuri; Kasuya, Eiiti

    2013-01-01

    The roles played by nonfatal secretions of adult anurans in the avoidance of predation remain unknown. The adult Wrinkled frog (Rana rugosa) has warty skin with the odorous mucus secretion that is not fatal to the snake Elaphe quadrivirgata. We fed R. rugosa or Fejervarya limnocharis, which resembles R. rugosa in appearance and has mucus secretion, to snakes and compared the snakes' responses to the frogs. Compared to F. limnocharis, R. rugosa was less frequently bitten or swallowed by snakes. The snakes that bit R. rugosa spat out the frogs and showed mouth opening (gaping) behavior, while the snakes that bit F. limnocharis did not show gaping behavior. We also compared the responses of the snakes to R. rugosa and F. limnocharis secretions. We coated palatable R. japonica with secretions from R. rugosa or F. limnocharis. The frogs coated by R. rugosa secretion were less frequently bitten or swallowed than those coated by F. limnocharis secretion. We concluded that compared to different frog species of similar sizes, the adult R. rugosa was less frequently preyed upon by, and that its skin secretion was effective in avoiding predation by snakes.

  8. New Wine in Old Skins: Changing Patterns in the Governing of the Adult Learner in Sweden

    Science.gov (United States)

    Fejes, Andreas

    2005-01-01

    This paper explores the ways in which the adult learner has been governed in recent years and whether the techniques for doing this have changed over the last 50 years. The focus is first on which adult subject (adult learner) is constructed in the material analysed. What kinds of subjects are governed? This is followed by an analysis of what…

  9. Ultrasonic stimulation of mouse skin reverses the healing delays in diabetes and aging by activation of Rac1

    OpenAIRE

    Roper, James A.; Williamson, Rosalind C.; Bally, Blandine; Cowell, Christopher AM; Brooks, Rebecca; Stephens, Phil; Harrison, Andrew J; Bass, Mark D.

    2015-01-01

    Chronic skin healing defects are one of the leading challenges to lifelong wellbeing, affecting 2-5% of populations. Chronic wound formation is linked to age and diabetes and frequently leads to major limb amputation. Here we identify a strategy to reverse fibroblast senescence and improve healing rates. In healthy skin, fibronectin activates Rac1 in fibroblasts, causing migration into the wound bed and driving wound contraction. We discover that mechanical stimulation of skin with ultrasound...

  10. Gross and microscopic lesions in the female SENCAR mouse skin and lung in tumor initiation and promotion studies.

    OpenAIRE

    Knutsen, G L; Kovatch, R M; Robinson, M.

    1986-01-01

    The skin and lung tissues from SENCAR mice used as part of the Environmental Protection Agency's (EPA's) Carcinogenesis Testing Matrix were examined. This study included SENCAR mice used in three different short-term bioassay protocols in which the skin papilloma assay was used to identify initiators, promoters, and complete carcinogens. Also included were the pathology findings from SENCAR mice used in the combined bioassay in which the skin assay and the lung adenoma assay were conducted si...

  11. Asymptomatic skin sensitization to birch predicts later development of birch pollen allergy in adults

    DEFF Research Database (Denmark)

    Bødtger, Uffe; Poulsen, Lars K; Malling, Hans-Jørgen

    2003-01-01

    birch skin prick test weal diameter of > or =4 mm, a positive conjunctival provocation test result, and specific IgE of > or =CAP class 2, as well as with the presence of other allergies. Specific IgE of > or =CAP class 2 was 87.5% predictive for allergy development, whereas a negative conjunctival...... risk is any subject with target organ sensitivity, an elevated specific IgE level, and/or a skin prick test weal diameter of >4 mm....

  12. Skin incision induces expression of axonal regeneration-related genes in adult rat spinal sensory neurons

    OpenAIRE

    Hill, Caitlin E.; Harrison, Benjamin J; Rau, Kris K.; Hougland, M. Tyler; Bunge, Mary Bartlett; Lorne M. Mendell; Petruska, Jeffrey C.

    2010-01-01

    Skin incision and nerve injury both induce painful conditions. Incisional and post-surgical pain is believed to arise primarily from inflammation of tissue and the subsequent sensitization of peripheral and central neurons. The role of axonal regeneration-related processes in development of pain has only been considered when there has been injury to the peripheral nerve itself, even though tissue damage likely induces injury of resident axons. We sought to determine if skin incision would aff...

  13. Angiotensin-converting enzyme inhibitor (enalapril maleate) accelerates recovery of mouse skin from UVB-induced wrinkles

    Energy Technology Data Exchange (ETDEWEB)

    Matsuura-Hachiya, Yuko; Arai, Koji Y.; Ozeki, Rieko; Kikuta, Ayako; Nishiyama, Toshio, E-mail: toshio_n@cc.tuat.ac.jp

    2013-12-06

    Highlights: •Angiotensin converting enzyme (ACE) increases in UVB-irradiated skin. •Administration of an ACE inhibitor improved UVB-induced skin wrinkle. •ACE inhibitor improved UVB-induced epidermal hypertrophy. •ACE inhibitor improved transepidermal water loss in the UVB-irradiated skin. -- Abstract: Angiotensin-converting enzyme (ACE) activity and angiotensin II signaling regulate cell proliferation, differentiation, and tissue remodeling, as well as blood pressure, while in skin, angiotensin II signaling is involved in wound healing, inflammation, and pathological scar formation. Therefore, we hypothesized that angiotensin II is also involved in photoaging of skin. In this study, we examined the effect of enalapril maleate, an ACE inhibitor, on recovery of wrinkled skin of hairless mice exposed to long-term UVB irradiation. Immunohistochemical observation revealed that expression of ACE, angiotensin II, and angiotensin II type 1 (AT1) and type 2 (AT2) receptors in the skin was increased after UVB irradiation (3 times/week at increasing intensities for 8 weeks). Administration of enalapril maleate (5 times/week for 6 weeks, starting 1 week after 10-week irradiation) accelerated recovery from UVB-induced wrinkles, epidermal hyperplasia and epidermal barrier dysfunction, as compared with the vehicle control. Our results indicate that ACE and angiotensin II activity are involved in skin photoaging, and suggest that ACE inhibitor such as enalapril maleate may have potential for improvement of photoaged skin.

  14. Nordihydroguaiaretic Acid from Creosote Bush (Larrea tridentata Mitigates 12-O-Tetradecanoylphorbol-13-Acetate-Induced Inflammatory and Oxidative Stress Responses of Tumor Promotion Cascade in Mouse Skin

    Directory of Open Access Journals (Sweden)

    Shakilur Rahman

    2011-01-01

    Full Text Available Nordihydroguaiaretic acid (NDGA is a phenolic antioxidant found in the leaves and twigs of the evergreen desert shrub, Larrea tridentata (Sesse and Moc. ex DC Coville (creosote bush. It has a long history of traditional medicinal use by the Native Americans and Mexicans. The modulatory effects of topically applied NDGA was studied on acute inflammatory and oxidative stress responses in mouse skin induced by stage I tumor promoting agent, 12-O-tetradecanoylphorbol-13-acetate (TPA. Double TPA treatment adversely altered many of the marker responses of stage I skin tumor promotion cascade. Pretreatment of NDGA in TPA-treated mice mitigated cutaneous lipid peroxidation and inhibited production of hydrogen peroxide. NDGA treatment also restored reduced glutathione level and activities of antioxidant enzymes. Elevated activities of myeloperoxidase, xanthine oxidase and skin edema formation in TPA-treated mice were also lowered by NDGA indicating a restrained inflammatory response. Furthermore, results of histological study demonstrated inhibitory effect of NDGA on cellular inflammatory responses. This study provides a direct evidence of antioxidative and anti-inflammatory properties of NDGA against TPA-induced cutaneous inflammation and oxidative stress corroborating its chemopreventive potential against skin cancer.

  15. Hepatocyte nuclear factor 4α is required for cell differentiation and homeostasis in the adult mouse gastric epithelium.

    Science.gov (United States)

    Moore, Benjamin D; Khurana, Shradha S; Huh, Won Jae; Mills, Jason C

    2016-08-01

    We have previously shown that the sequential transcription factors Xbp1→Mist1 (Bhlha15) govern the ultrastructural maturation of the secretory apparatus in enzyme-secreting zymogenic chief cells (ZCs) in the gastric unit. Here we sought to identify transcriptional regulators upstream of X-box binding protein 1 (XBP1) and MIST1. We used immunohistochemistry to characterize Hnf4α(flox/flox) adult mouse stomachs after tamoxifen-induced deletion of Hnf4α We used qRT-PCR, Western blotting, and chromatin immunoprecipitation to define the molecular interaction between hepatocyte nuclear factor 4 alpha (HNF4α) and Xbp1 in mouse stomach and human gastric cells. We show that HNF4α protein is expressed in pit (foveolar) cells, mucous neck cells, and zymogenic chief cells (ZCs) of the corpus gastric unit. Loss of HNF4α in adult mouse stomach led to reduced ZC size and ER content, phenocopying previously characterized effects of Xbp1 deletion. However, HNF4α(Δ/Δ) stomachs also exhibited additional phenotypes including increased proliferation in the isthmal stem cell zone and altered mucous neck cell migration, indicating a role of HNF4α in progenitor cells as well as in ZCs. HNF4α directly occupies the Xbp1 promoter locus in mouse stomach, and forced HNF4α expression increased abundance of XBP1 mRNA in human gastric cancer cells. Finally, as expected, loss of HNF4α caused decreased Xbp1 and Mist1 expression in mouse stomachs. We show that HNF4α regulates homeostatic proliferation in the gastric epithelium and is both necessary and sufficient for the upstream regulation of the Xbp1→Mist1 axis in maintenance of ZC secretory architecture. PMID:27340127

  16. Skin-piercing blood-sucking moths II: Studies on a further 3 adult Calyptra [Calpe] sp. (Lepid., Noctuidae).

    Science.gov (United States)

    Bänziger, H

    1979-03-01

    1. Of the scarce Calyptra minuticornis, C. orthograpta and C. labilis, 51, 24, and 7 adults, respectively, were observed during some 600 night inspections at over 100 sites in 1965--1967 and 1971--1977. 2. Hitherto biologically completely unknown, and not recorded before in S.E. Asia, the latter two species flew in or near tropical monsoon forests in hilly regions (300--600 m) of N. Thailand (C. orthograpta also N. Laos). C. minuticornis was found in these and in tropical evergreen and semi-evergreen rain forests of S. Thailand and N.W. Malaysia. 3. In N. Thailand the three species were more common at the end of the cool season/start of the hot season and at the start of the rainy season. They were active mainly during the first half of the night 4. Flight and piercing behaviour, alighting, resting, enemies, and the lack of females, were similar to virtually identical with the "classical" skin-piercing blood-sucking C. eustrigata. 5. C. labilis was seen attacking elephant, C. orthograpta also water buffalo and sambar, C. minuticornis also zebu and tapir but not sambar. C. minuticornis settled on man also but did not pierce. 6. Through no piercing of hosts' skin has actually been seen in nature, indirect evidence suggests that the 3 moths are likely to be occasional blood-suckers. They pierced and sucked blood from the author's skin in experiments. 7. Reasons for lack of direct evidence may be: less developed hematophagy, less favoured hosts, lack of easy-to-pierce injured skin (which also trigger the piercing response), different climatic and phytoecological environment, fewer specimens than in the case of C. eustrigata. 8. Field observations and experiments indicate that the closely related, fruit-piercing Oraesia emarginata is not skin-piercing blood-sucking--a habit likely to be exhibited mainly in humid equatorial regions by a few Calyptra only. PMID:35931

  17. Effects of age, gender, BMI, and anatomical site on skin thickness in children and adults with diabetes.

    Directory of Open Access Journals (Sweden)

    José G B Derraik

    Full Text Available OBJECTIVE: We aimed to assess the effects of age, sex, body mass index (BMI, and anatomical site on skin thickness in children and adults with diabetes. METHODS: We studied 103 otherwise healthy children and adolescents with type 1 diabetes aged 5-19 years, and 140 adults with type 1 and type 2 diabetes aged 20-85 years. The thicknesses of both the dermis and subcutis were assessed using ultrasound with a linear array transducer, on abdominal and thigh skin. RESULTS: There was an age-related thickening of both dermis (p<0.0001 and subcutis (p = 0.013 in children and adolescents. Girls displayed a substantial pubertal increase in subcutis of the thigh (+54%; p = 0.048 and abdomen (+68%; p = 0.009. Adults showed an age-related decrease in dermal (p = 0.021 and subcutis (p = 0.009 thicknesses. Pubertal girls had a thicker subcutis than pubertal boys in both thigh (16.7 vs 7.5 mm; p<0.0001 and abdomen (16.7 vs 8.8 mm; p<0.0001. Men had greater thigh dermal thickness than women (1.89 vs 1.65 mm; p = 0.003, while the subcutis was thicker in women in thigh (21.3 vs 17.9 mm; p = 0.012 and abdomen (17.7 vs 9.8 mm; p<0.0001. In boys, men, and women, both dermis and subcutis were thicker on the abdomen compared to thigh; in girls this was only so for dermal thickness. In both children and adults, the skin (dermis and subcutis became steadily thicker with increasing BMI (p<0.0001. CONCLUSIONS: Skin thickness is affected by age, pubertal status, gender, BMI, and anatomical site. Such differences may be important when considering appropriate sites for dermal/subcutaneous injections and other transdermal delivery systems.

  18. Brief Isoflurane Anesthesia Produces Prominent Phosphoproteomic Changes in the Adult Mouse Hippocampus.

    Science.gov (United States)

    Kohtala, Samuel; Theilmann, Wiebke; Suomi, Tomi; Wigren, Henna-Kaisa; Porkka-Heiskanen, Tarja; Elo, Laura L; Rokka, Anne; Rantamäki, Tomi

    2016-06-15

    Anesthetics are widely used in medical practice and experimental research, yet the neurobiological basis governing their effects remains obscure. We have here used quantitative phosphoproteomics to investigate the protein phosphorylation changes produced by a 30 min isoflurane anesthesia in the adult mouse hippocampus. Altogether 318 phosphorylation alterations in total of 237 proteins between sham and isoflurane anesthesia were identified. Many of the hit proteins represent primary pharmacological targets of anesthetics. However, findings also enlighten the role of several other proteins-implicated in various biological processes including neuronal excitability, brain energy homeostasis, synaptic plasticity and transmission, and microtubule function-as putative (secondary) targets of anesthetics. In particular, isoflurane increases glycogen synthase kinase-3β (GSK3β) phosphorylation at the inhibitory Ser(9) residue and regulates the phosphorylation of multiple proteins downstream and upstream of this promiscuous kinase that regulate diverse biological functions. Along with confirmatory Western blot data for GSK3β and p44/42-MAPK (mitogen-activated protein kinase; reduced phosphorylation of the activation loop), we observed increased phosphorylation of microtubule-associated protein 2 (MAP2) on residues (Thr(1620,1623)) that have been shown to render its dissociation from microtubules and alterations in microtubule stability. We further demonstrate that diverse anesthetics (sevoflurane, urethane, ketamine) produce essentially similar phosphorylation changes on GSK3β, p44/p42-MAPK, and MAP2 as observed with isoflurane. Altogether our study demonstrates the potential of quantitative phosphoproteomics to study the mechanisms of anesthetics (and other drugs) in the mammalian brain and reveals how already a relatively brief anesthesia produces pronounced phosphorylation changes in multiple proteins in the central nervous system. PMID:27074656

  19. Effect of cyanotoxins on the hypothalamic-pituitary-gonadal axis in male adult mouse.

    Directory of Open Access Journals (Sweden)

    Xiaolu Xiong

    Full Text Available BACKGROUND: Microcystins LR (MC-LR are hepatotoxic cyanotoxins that have been shown to induce reproductive toxicity, and Hypothalamic-Pituitary-Gonadal Axis (HPG is responsible for the control of reproductive functions. However, few studies have been performed to evaluate the effects of MC-LR on HPG axis. This study aimed to investigate the MC-LR-induced toxicity in the reproductive system of mouse and focus on the HPG axis. METHODS: Adult male C57BL/6 mice were exposed to various concentrations of MC-LR (0, 3.75, 7.50, 15.00 and 30.00 µg/kg body weight per day for 1 to 14 days, and it was found that exposure to different concentrations of MC-LR significantly disturbed sperm production in the mice testes in a dose- and time-dependent manner. To elucidate the associated possible mechanisms, the serum levels of testosterone, follicle-stimulating hormone (FSH and luteinizing hormone (LH were assessed. Meanwhile, PCR assays were employed to detect alterations in a series of genes involved in HPG axis, such as FSH, LH, gonadotropin-releasing hormone (GnRH and their complement receptors. Furthermore, the effect of MC-LR on the viability and testosterone production of Leydig cells were tested in vitro. RESULTS: MC-LR significantly impaired the spermatogenesis of mice possibly through the direct or indirect inhibition of GnRH synthesis at the hypothalamic level, which resulted in reduction of serum levels of LH that lead to suppression of testosterone production in the testis of mice. CONCLUSIONS: MC-LR may be a GnRH toxin that would disrupt the reproductive system of mice.

  20. Human atopic dermatitis skin-derived T cells can induce a reaction in mouse keratinocytes in vivo

    DEFF Research Database (Denmark)

    Martel, Britta C; Blom, Lars; Dyring-Andersen, Beatrice;

    2015-01-01

    through keratinocyte activation and consequently cause development of eczematous lesions. Punch biopsies of lesional skin from AD patients were used to establish skin-derived T cell cultures and which were transferred into NOD.Cg-Prkd(scid) Il2rg(tm1Sug) /JicTac (NOG) mice. We found that subcutaneous...

  1. Overexpression of constitutively active BMP-receptor-IB in mouse skin causes an ichthyosis-vulgaris-like disease.

    Science.gov (United States)

    Yu, Xueyan; Espinoza-Lewis, Ramón A; Sun, Cheng; Lin, Lisong; He, Fenglei; Xiong, Wei; Yang, Jing; Wang, Alun; Chen, Yiping

    2010-12-01

    The skin is the outer layer of protection against the environment. The development and formation of the skin is regulated by several genetic cascades including the bone morphogenetic protein (BMP) signaling pathway, which has been suggested to play an important role during embryonic organ development. Several skin defects and diseases are caused by genetic mutations or disorders. Ichthyosis is a common genetic skin disorder characterized by dry scaly skin. Loss-of-function mutations in the filaggrin (FLG) gene have been identified as the cause of the ichthyosis vulgaris (IV) phenotype; however, the direct regulation of filaggrin expression in vivo is unknown. We present evidence that BMP signaling regulates filaggrin expression in the epidermis. Mice expressing a constitutively active form of BMP-receptor-IB in the developing epidermis exhibit a phenotype resembling IV in humans, including dry flaky skin, compact hyperkeratosis, and an attenuated granular layer associated with a significantly downregulated expression of filaggrin. Regulation of filaggrin expression by BMP signaling has been further confirmed by the application of exogenous BMP2 in skin explants and by a transgenic model overexpressing Noggin in the epidermis. Our results demonstrate that aberrant BMP signaling in the epidermis causes overproliferation and hyperkeratinization, leading to an IV-like skin disease.

  2. The impact of maternal separation on adult mouse behaviour and on the total neuron number in the mouse hippocampus

    DEFF Research Database (Denmark)

    Fabricius, K.; Wörtwein, Gitta; Pakkenberg, B.

    2008-01-01

    The maternal separation paradigm has been applied to C57BL/6J mice as an animal developmental model for understanding structural deficits leading to abnormal behaviour. A maternal separation (MS) model was used on postnatal day (PND) 9, where the pups were removed from their mother for 24 h (MS24......). When the pups were 10 weeks old, the level of anxiety and fear was measured with two behavioural tests; an open field test and an elevated plus maze test. The Barnes platform maze was used to test spatial learning, and memory by using acquisition trials followed by reverse trial sessions. The MS24 mice...... to controls. Apparently a single maternal separation can impact the number of neurons in mouse hippocampus either by a decrease of neurogenesis or as an increase in neuron apoptosis. This study is the first to assess the result of maternal separation combining behaviour and stereology Udgivelsesdato: 2008/2...

  3. Disruption of Ah Receptor Signaling during Mouse Development Leads to Abnormal Cardiac Structure and Function in the Adult.

    Directory of Open Access Journals (Sweden)

    Vinicius S Carreira

    Full Text Available The Developmental Origins of Health and Disease (DOHaD Theory proposes that the environment encountered during fetal life and infancy permanently shapes tissue physiology and homeostasis such that damage resulting from maternal stress, poor nutrition or exposure to environmental agents may be at the heart of adult onset disease. Interference with endogenous developmental functions of the aryl hydrocarbon receptor (AHR, either by gene ablation or by exposure in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, a potent AHR ligand, causes structural, molecular and functional cardiac abnormalities and altered heart physiology in mouse embryos. To test if embryonic effects progress into an adult phenotype, we investigated whether Ahr ablation or TCDD exposure in utero resulted in cardiac abnormalities in adult mice long after removal of the agent. Ten-months old adult Ahr-/- and in utero TCDD-exposed Ahr+/+ mice showed sexually dimorphic abnormal cardiovascular phenotypes characterized by echocardiographic findings of hypertrophy, ventricular dilation and increased heart weight, resting heart rate and systolic and mean blood pressure, and decreased exercise tolerance. Underlying these effects, genes in signaling networks related to cardiac hypertrophy and mitochondrial function were differentially expressed. Cardiac dysfunction in mouse embryos resulting from AHR signaling disruption seems to progress into abnormal cardiac structure and function that predispose adults to cardiac disease, but while embryonic dysfunction is equally robust in males and females, the adult abnormalities are more prevalent in females, with the highest severity in Ahr-/- females. The findings reported here underscore the conclusion that AHR signaling in the developing heart is one potential target of environmental factors associated with cardiovascular disease.

  4. Sarcophine-diol, a skin cancer chemopreventive agent, inhibits proliferation and stimulates apoptosis in mouse melanoma B₁₆F₁₀ cell line.

    Science.gov (United States)

    Szymanski, Pawel T; Kuppast, Bhimanna; Ahmed, Safwat A; Khalifa, Sherief; Fahmy, Hesham

    2012-01-01

    Sarcodiol (SD) is a semi-synthetic derivative of sarcophine, a marine natural product. In our previous work, we reported the significant chemopreventive effects of SD against non-melanoma skin cancer both in vitro and in vivo mouse models. In this investigation, we extended this work to study the effect of sarcodiol on melanoma development, the more deadly form of skin cancer, using the mouse melanoma B₁₆F₁₀ cell line. In this study we report that SD inhibits the de novo DNA synthesis and enhances fragmentation of DNA. We also evaluated the antitumor effect of SD on melanoma cell viability using several biomarkers for cell proliferation and apoptosis. SD inhibits the expression levels of signal transducers and activators of transcription protein (STAT-3) and cyclin D1, an activator of cyclin-dependent kinase 4 (Cdk4). SD treatment also enhances cellular level of tumor suppressor protein 53 (p53) and stimulates cleavage of the nuclear poly (ADP-ribose) polymerase (cleaved-PARP). SD also enhances cellular levels of cleaved Caspase-3, -8, -9 and stimulates enzymatic activities of Caspase-3, -8 and -9. These results, in addition to inhibition of cell viability, suggest that SD inhibits melanoma cell proliferation by arresting the cell-division cycle in a Go quiescent phase and activates programmed cell death (apoptosis) via extrinsic and intrinsic pathways. Finally, these studies demonstrate that SD shows a very promising chemopreventive effect in melanoma B₁₆F₁₀ tumor cells. PMID:22363217

  5. Sarcophine-Diol, a Skin Cancer Chemopreventive Agent, Inhibits Proliferation and Stimulates Apoptosis in Mouse Melanoma B16F10 Cell Line

    Directory of Open Access Journals (Sweden)

    Hesham Fahmy

    2011-12-01

    Full Text Available Sarcodiol (SD is a semi-synthetic derivative of sarcophine, a marine natural product. In our previous work, we reported the significant chemopreventive effects of SD against non-melanoma skin cancer both in vitro and in vivo mouse models. In this investigation, we extended this work to study the effect of sarcodiol on melanoma development, the more deadly form of skin cancer, using the mouse melanoma B16F10 cell line. In this study we report that SD inhibits the de novo DNA synthesis and enhances fragmentation of DNA. We also evaluated the antitumor effect of SD on melanoma cell viability using several biomarkers for cell proliferation and apoptosis. SD inhibits the expression levels of signal transducers and activators of transcription protein (STAT-3 and cyclin D1, an activator of cyclin-dependent kinase 4 (Cdk4. SD treatment also enhances cellular level of tumor suppressor protein 53 (p53 and stimulates cleavage of the nuclear poly (ADP-ribose polymerase (cleaved-PARP. SD also enhances cellular levels of cleaved Caspase-3, -8, -9 and stimulates enzymatic activities of Caspase-3, -8 and -9. These results, in addition to inhibition of cell viability, suggest that SD inhibits melanoma cell proliferation by arresting the cell-division cycle in a Go quiescent phase and activates programmed cell death (apoptosis via extrinsic and intrinsic pathways. Finally, these studies demonstrate that SD shows a very promising chemopreventive effect in melanoma B16F10 tumor cells.

  6. Sarcophine-diol, a skin cancer chemopreventive agent, inhibits proliferation and stimulates apoptosis in mouse melanoma B₁₆F₁₀ cell line.

    Science.gov (United States)

    Szymanski, Pawel T; Kuppast, Bhimanna; Ahmed, Safwat A; Khalifa, Sherief; Fahmy, Hesham

    2012-01-01

    Sarcodiol (SD) is a semi-synthetic derivative of sarcophine, a marine natural product. In our previous work, we reported the significant chemopreventive effects of SD against non-melanoma skin cancer both in vitro and in vivo mouse models. In this investigation, we extended this work to study the effect of sarcodiol on melanoma development, the more deadly form of skin cancer, using the mouse melanoma B₁₆F₁₀ cell line. In this study we report that SD inhibits the de novo DNA synthesis and enhances fragmentation of DNA. We also evaluated the antitumor effect of SD on melanoma cell viability using several biomarkers for cell proliferation and apoptosis. SD inhibits the expression levels of signal transducers and activators of transcription protein (STAT-3) and cyclin D1, an activator of cyclin-dependent kinase 4 (Cdk4). SD treatment also enhances cellular level of tumor suppressor protein 53 (p53) and stimulates cleavage of the nuclear poly (ADP-ribose) polymerase (cleaved-PARP). SD also enhances cellular levels of cleaved Caspase-3, -8, -9 and stimulates enzymatic activities of Caspase-3, -8 and -9. These results, in addition to inhibition of cell viability, suggest that SD inhibits melanoma cell proliferation by arresting the cell-division cycle in a Go quiescent phase and activates programmed cell death (apoptosis) via extrinsic and intrinsic pathways. Finally, these studies demonstrate that SD shows a very promising chemopreventive effect in melanoma B₁₆F₁₀ tumor cells.

  7. miR-206-3p在小鼠皮肤中的表达及其作用%Expression and distribution of miR-206-3p in mouse skin and its potential roles

    Institute of Scientific and Technical Information of China (English)

    穆原; 周红; 李文艳; 李耀武

    2013-01-01

    Objective To investigate the expression and distribution of miR-206-3p and its target gene Bdnf (brain-derived neurotrophic factor) in mouse skin and the potential roles during the development of skin.Methods The full-thickness back skins of BALB/c mice on the 13.5 dpc (day post coition),15.5 dpc,17.5 dpc,1 dpp (day post partum),4 dpp and 16 weeks were collected respectively.The expression levels of miR-206-3p and BdnfmRNA were measured by real time RT-PCR,and BDNF protein was detected by western blot.The distributions of miR-206-3p and BDNF in tissue were profiled by in situ hybridization (ISH) and immunohistochemistry (IHC) respectively.Results The expression level of miR-206-3p increased gradually until 17.5 dpc and subsequently receded to the similar level of the 13.5 dpc during adult stage.The expression of BDNF protein exhibited in the opposite manner of miR-206-3p but BdnfmRNA remained stable from the 17.5 dpc until adult stage.ISH results showed that the distribution of miR-206-3p was gradually regionalized during the development of skin in the postnatal days and mainly located in the suprabasal layer and periphery of hair follicles,which was adjacent to the regions of BDNF expression at the same stage in a nonoverlapping manner.Conclusion The miR-206-3p may be involved in neurodevelopment of mouse skin through the post-transcriptional regulation of Bdnf.%目的 对小鼠皮肤中miR-206-3p及其靶基因脑源性神经营养因子(Bdnf)进行表达与定位检测,以探讨其在皮肤发育过程中的可能作用.方法 手术剪取13.5 dpc(交配后天数)、15.5 dpc、17.5 dpc胎鼠,1 dpp(出生后天数)、4 dpp乳鼠及16周龄雄鼠的背部全层皮肤,用实时荧光定量RT-PCR检测miR-206-3p与Bdnf mRNA的表达水平,western blot检测BDNF蛋白质表达水平,原位杂交与免疫组化分别检测miR-206-3p与BDNF的组织定位.结果 皮肤中miR-206-3p在胚胎期持续升高,到17.5 dpc后逐渐降低,于成年鼠时回复至13.5 dpc时

  8. Chemopreventive effect of resveratrol, sesamol, sesame oil and sunflower oil in the Epstein-Barr virus early antigen activation assay and the mouse skin two-stage carcinogenesis.

    Science.gov (United States)

    Kapadia, Govind J; Azuine, Magnus A; Tokuda, Harukuni; Takasaki, Midori; Mukainaka, Teruo; Konoshima, Takao; Nishino, Hoyoku

    2002-06-01

    Resveratrol, sesamol, sesame oil and sunflower oil are known natural dietary components with intrinsic cancer chemopreventive potentials. As a part of our study of dietary constituents as potential cancer chemopreventive agents, we have assessed the anti-cancer potentials of these products in the promotion stage of cancer development employing the in vitro Epstein-Barr virus early antigen activation assay induced by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). Further, we studied the activities of these compounds in the brine shrimp cytotoxicity assay as well as on the stable 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging bioassay with a view to comparing some of the mechanisms of their anti-cancer activity. Finally, we compared the observed chemoprotective capabilities of the four products in the in vivo 7,12 dimethylbenz(a)anthracene initiated and TPA-promoted mouse skin two-stage carcinogenesis protocols. All the products tested showed a profound inhibitory effect on the Epstein-Barr virus early antigen induction using Raji cells. Comparatively, sesame oil was the most potent followed by sesamol and then resveratrol. Only sesamol and resveratrol showed a remarkable cytotoxic activity in the brine shrimp lethality assays as well as profound free radical scavenging activity in the DPPH bioassay. In both test systems, sesamol exhibited a more remarkable activity than resveratrol while sesame oil and sunflower oil did not exhibit any appreciable activity even at the highest concentrations tested (4000 microg ml(-1) ). In our in vivo assay at a 50-fold molar ratio to TPA, sesamol offered 50% reduction in mouse skin papillomas at 20 weeks after promotion with TPA. Under an identical molar ratio to TPA, resveratrol offered a 60% reduction in the papillomas in mouse at 20 weeks. Thus sesamol seems to be an almost equally potent chemopreventive agent. Sesame oil and sunflower oil offered 20 and 40% protection, respectively, in the mouse

  9. The risk of hydroquinone and sunscreen over-absorption via photodamaged skin is not greater in senescent skin as compared to young skin: nude mouse as an animal model.

    Science.gov (United States)

    Hung, Chi-Feng; Chen, Wei-Yu; Aljuffali, Ibrahim A; Shih, Hui-Chi; Fang, Jia-You

    2014-08-25

    Intrinsic aging and photoaging modify skin structure and components, which subsequently change percutaneous absorption of topically applied permeants. The purpose of this study was to systematically evaluate drug/sunscreen permeation via young and senescent skin irradiated by ultraviolet (UV) light. Both young and senescent nude mice were subjected to UVA (10 J/cm(2)) and/or UVB radiation (175 mJ/cm(2)). Physiological parameters, immunohistology, and immunoblotting were employed to examine the aged skin. Hydroquinone and sunscreen permeation was determined by in vitro Franz cell. In vivo skin absorption was documented using a hydrophilic dye, rhodamine 123 (log P=-0.4), as a permeant. UVA exposure induced cyclooxygenase (COX)-2 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) upregulation. Epidermal tight junction (TJ) were degraded by UVA. UVB increased transepidermal water loss (TEWL) from 13 to 24 g/m(2)/h. Hyperplasia and inflammation, but not loss of TJ, were also observed in UVB-treated skin. UVA+UVB- and UVA-irradiated skin demonstrated similar changes in histology and biomarkers. UVA+UVB or UVA exposure increased hydroquinone flux five-fold. A negligible alteration of hydroquinone permeation was shown with UVB exposure. Hydroquinone exhibited a lower penetration through senescent skin than young skin. Both UVA and UVB produced enhancement of oxybenzone flux and skin uptake. However, the amount of increase was less than that of hydroquinone delivery. Photoaging did not augment skin absorption of sunscreens with higher lipophilicity, including avobenzone and ZnO. Exposure to UVA generally increased follicular entrance of these permeants, which showed two- to three-fold greater follicular uptake compared to the untreated group. Photoaging had less impact on drug/sunscreen absorption with more lipophilic permeants. Percutaneous absorption did not increase in skin subjected to both intrinsic and extrinsic aging. PMID:24858384

  10. Changes in skin test reactivity among adults with atopic disease: a 3-year prospective study

    DEFF Research Database (Denmark)

    Aslund, N.; Thomsen, S.F.; Molgaard, E.;

    2008-01-01

    , 186 candidates, ranging in age from 14 to 44 years, who in a screening questionnaire reported symptoms suggestive of respiratory allergic disease, 344 individuals with a positive skin prick test (SPT) result concomitantly with asthma and/or rhinitis were clinically studied on 2 occasions, 3 years...

  11. Prevention and treatment of intertrigo in large skin folds of adults: a systematic review.

    NARCIS (Netherlands)

    Mistiaen, P.; Halm-Walters, M. van

    2010-01-01

    Background: Intertrigo in the large skin folds is a common problem. There is a plethora of treatments, but a lack of evidence about their efficacy. A nursing guideline on this matter had to be updated and broadened in scope to other health care professionals. Methods: A systematic review was perform

  12. Huntingtin acts non cell-autonomously on hippocampal neurogenesis and controls anxiety-related behaviors in adult mouse.

    Directory of Open Access Journals (Sweden)

    Patrick Pla

    Full Text Available Huntington's disease (HD is a fatal neurodegenerative disease, characterized by motor defects and psychiatric symptoms, including mood disorders such as anxiety and depression. HD is caused by an abnormal polyglutamine (polyQ expansion in the huntingtin (HTT protein. The development and analysis of various mouse models that express pathogenic polyQ-HTT revealed a link between mutant HTT and the development of anxio-depressive behaviors and various hippocampal neurogenesis defects. However, it is unclear whether such phenotype is linked to alteration of HTT wild-type function in adults. Here, we report the analysis of a new mouse model in which HTT is inducibly deleted from adult mature cortical and hippocampal neurons using the CreER(T2/Lox system. These mice present defects in both the survival and the dendritic arborization of hippocampal newborn neurons. Our data suggest that these non-cell autonomous effects are linked to defects in both BDNF transport and release upon HTT silencing in hippocampal neurons, and in BDNF/TrkB signaling. The controlled deletion of HTT also had anxiogenic-like effects. Our results implicate endogenous wild-type HTT in adult hippocampal neurogenesis and in the control of mood disorders.

  13. Multipotential stem cells from the adult mouse brain proliferate and self-renew in response to basic fibroblast growth factor.

    Science.gov (United States)

    Gritti, A; Parati, E A; Cova, L; Frolichsthal, P; Galli, R; Wanke, E; Faravelli, L; Morassutti, D J; Roisen, F; Nickel, D D; Vescovi, A L

    1996-02-01

    It has been established that the adult mouse forebrain contains multipotential (neuronal/glial) progenitor cells that can be induced to proliferate in vitro when epidermal growth factor is provided. These cells are found within the subventricular zone of the lateral ventricles, together with other progenitor cell populations, whose requirements for proliferation remain undefined. Using basic fibroblast growth factor (bFGF), we have isolated multipotential progenitors from adult mouse striatum. These progenitors proliferate and can differentiate into cells displaying the antigenic properties of astrocytes, oligodendrocytes, and neurons. The neuron-like cells possess neuronal features, exhibit neuronal electrophysiological properties, and are immunoreactive for GABA, substance P, choline acetyl-transferase, and glutamate. Clonal analysis confirmed the multipotency of these bFGF-dependent cells. Most significantly, subcloning experiments demonstrated that they were capable of self-renewal, which led to a progressive increase in population size over serial passaging. These results demonstrate that bFGF is mitogenic for multipotential cells from adult mammalian forebrain that possess stem cell properties. PMID:8558238

  14. Fibroblast growth factor 10 alters the balance between goblet and Paneth cells in the adult mouse small intestine.

    Science.gov (United States)

    Al Alam, Denise; Danopoulos, Soula; Schall, Kathy; Sala, Frederic G; Almohazey, Dana; Fernandez, G Esteban; Georgia, Senta; Frey, Mark R; Ford, Henri R; Grikscheit, Tracy; Bellusci, Saverio

    2015-04-15

    Intestinal epithelial cell renewal relies on the right balance of epithelial cell migration, proliferation, differentiation, and apoptosis. Intestinal epithelial cells consist of absorptive and secretory lineage. The latter is comprised of goblet, Paneth, and enteroendocrine cells. Fibroblast growth factor 10 (FGF10) plays a central role in epithelial cell proliferation, survival, and differentiation in several organs. The expression pattern of FGF10 and its receptors in both human and mouse intestine and their role in small intestine have yet to be investigated. First, we analyzed the expression of FGF10, FGFR1, and FGFR2, in the human ileum and throughout the adult mouse small intestine. We found that FGF10, FGFR1b, and FGFR2b are expressed in the human ileum as well as in the mouse small intestine. We then used transgenic mouse models to overexpress Fgf10 and a soluble form of Fgfr2b, to study the impact of gain or loss of Fgf signaling in the adult small intestine. We demonstrated that overexpression of Fgf10 in vivo and in vitro induces goblet cell differentiation while decreasing Paneth cells. Moreover, FGF10 decreases stem cell markers such as Lgr5, Lrig1, Hopx, Ascl2, and Sox9. FGF10 inhibited Hes1 expression in vitro, suggesting that FGF10 induces goblet cell differentiation likely through the inhibition of Notch signaling. Interestingly, Fgf10 overexpression for 3 days in vivo and in vitro increased the number of Mmp7/Muc2 double-positive cells, suggesting that goblet cells replace Paneth cells. Further studies are needed to determine the mechanism by which Fgf10 alters cell differentiation in the small intestine.

  15. Hesperidin methyl chalcone inhibits oxidative stress and inflammation in a mouse model of ultraviolet B irradiation-induced skin damage.

    Science.gov (United States)

    Martinez, Renata M; Pinho-Ribeiro, Felipe A; Steffen, Vinicius S; Caviglione, Carla V; Vignoli, Josiane A; Baracat, Marcela M; Georgetti, Sandra R; Verri, Waldiceu A; Casagrande, Rubia

    2015-07-01

    Hesperidin methyl chalcone (HMC) is a safe flavonoid used to treat chronic venous diseases, but its effects and mechanisms on UVB irradiation-induced inflammation and oxidative stress have never been described in vivo. Thus, the purpose of this study was to evaluate the effects of systemic administration of HMC in skin oxidative stress and inflammation induced by UVB irradiation. To induce skin damage, hairless mice were exposed to an acute UVB irradiation dose of 4.14 J/cm(2), and the dorsal skin samples were collected to evaluate oxidative stress and inflammatory response. The intraperitoneal treatment with HMC at the dose of 300 mg/kg inhibited UVB irradiation-induced skin edema, neutrophil recruitment, and matrix metalloproteinase-9 activity. HMC also protected the skin from UVB irradiation-induced oxidative stress by maintaining ferric reducing antioxidant power (FRAP), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS) scavenging ability and antioxidant levels (reduced glutathione and catalase). Corroborating, HMC inhibited UVB irradiation-induced superoxide anion generation and gp91phox (NADPH oxidase subunit) mRNA expression. Furthermore, the antioxidant effect of HMC resulted in lower production of inflammatory mediators, including lipid hydroperoxides and a wide range of cytokines. Taken together, these results unveil a novel applicability of HMC in the treatment of UVB irradiation-induced skin inflammation and oxidative stress.

  16. In Vivo Spectrum of UVC-induced Mutation in Mouse Skin Epidermis May Reflect the Cytosine Deamination Propensity of Cyclobutane Pyrimidine Dimers.

    Science.gov (United States)

    Ikehata, Hironobu; Mori, Toshio; Yamamoto, Masayuki

    2015-11-01

    Although ultraviolet radiation (UVR) has a genotoxicity for inducing skin cancers, the skin may tolerate UVC component because the epidermal layer prevents this short wavelength range from passing through. Here, UVC genotoxicity for mouse skin was evaluated in terms of DNA damage formation and mutagenicity. UVC induced UVR photolesions and mutations remarkably in the epidermis but poorly in the dermis, confirming the barrier ability of the epidermis against shorter UVR wavelengths. Moreover, the epidermis itself responded to UVC mutagenicity with mutation induction suppression, which suppressed the mutant frequencies to a remarkably low, constant level regardless of UVC dose. The mutation spectrum observed in UVC-exposed epidermis showed a predominance of UV-signature mutation, which occurred frequently in 5'-TCG-3', 5'-TCA-3' and 5'-CCA-3' contexts. Especially, for the former two contexts, the mutations recurred at several sites with more remarkable recurrences at the 5'-TCG-3' sites. Comparison of the UVC mutation spectrum with those observed in longer UVR wavelength ranges led us to a mechanism that explains why the sequence context preference of UV-signature mutation changes according to the wavelength, which is based on the difference in the mCpG preference of cyclobutane pyrimidine dimer (CPD) formation among UVR ranges and the sequence context-dependent cytosine deamination propensity of CPD.

  17. In Vivo Spectrum of UVC-induced Mutation in Mouse Skin Epidermis May Reflect the Cytosine Deamination Propensity of Cyclobutane Pyrimidine Dimers.

    Science.gov (United States)

    Ikehata, Hironobu; Mori, Toshio; Yamamoto, Masayuki

    2015-11-01

    Although ultraviolet radiation (UVR) has a genotoxicity for inducing skin cancers, the skin may tolerate UVC component because the epidermal layer prevents this short wavelength range from passing through. Here, UVC genotoxicity for mouse skin was evaluated in terms of DNA damage formation and mutagenicity. UVC induced UVR photolesions and mutations remarkably in the epidermis but poorly in the dermis, confirming the barrier ability of the epidermis against shorter UVR wavelengths. Moreover, the epidermis itself responded to UVC mutagenicity with mutation induction suppression, which suppressed the mutant frequencies to a remarkably low, constant level regardless of UVC dose. The mutation spectrum observed in UVC-exposed epidermis showed a predominance of UV-signature mutation, which occurred frequently in 5'-TCG-3', 5'-TCA-3' and 5'-CCA-3' contexts. Especially, for the former two contexts, the mutations recurred at several sites with more remarkable recurrences at the 5'-TCG-3' sites. Comparison of the UVC mutation spectrum with those observed in longer UVR wavelength ranges led us to a mechanism that explains why the sequence context preference of UV-signature mutation changes according to the wavelength, which is based on the difference in the mCpG preference of cyclobutane pyrimidine dimer (CPD) formation among UVR ranges and the sequence context-dependent cytosine deamination propensity of CPD. PMID:26335024

  18. Induced Neural Stem Cells Achieve Long-Term Survival and Functional Integration in the Adult Mouse Brain

    OpenAIRE

    Kathrin Hemmer; Mingyue Zhang; Thea van Wüllen; Marna Sakalem; Natalia Tapia; Aidos Baumuratov; Christian Kaltschmidt; Barbara Kaltschmidt; Hans R. Schöler; Weiqi Zhang; Jens C. Schwamborn

    2014-01-01

    Summary Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]). iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC) technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear ...

  19. "The preadipocyte factor" DLK1 marks adult mouse adipose tissue residing vascular cells that lack in vitro adipogenic differentiation potential

    DEFF Research Database (Denmark)

    Andersen, Ditte Caroline; Jensen, Line; Schrøder, Henrik Daa;

    2009-01-01

    Delta-like 1 (Dlk1) is expressed in 3T3-L1 preadipocytes and has frequently been referred to as "the" preadipocyte marker, yet the phenotype of DLK1(+) cells in adipose tissue remains undetermined. Herein, we demonstrate that DLK1(+) cells encompass around 1-2% of the adult mouse adipose stromal......, generation of tube-like structures on matrigel, and uptake of Acetylated Low Density-Lipoprotein, all characteristics of endothelial cells. We therefore suggest that DLK1(+)SVF cells are of a vascular origin and not them-selves committed preadipocytes as assumed hitherto....

  20. Isolation and Assessment of Single Long-Term Reconstituting Hematopoietic Stem Cells from Adult Mouse Bone Marrow.

    Science.gov (United States)

    Kent, David G; Dykstra, Brad J; Eaves, Connie J

    2016-01-01

    Hematopoietic stem cells with long-term repopulating activity can now be routinely obtained at purities of 40% to 50% from suspensions of adult mouse bone marrow. Here we describe robust protocols for both their isolation as CD45(+) EPCR(+) CD150(+) CD48(-) (ESLAM) cells using multiparameter cell sorting and for tracking their clonal growth and differentiation activity in irradiated mice transplanted with single ESLAM cells. The simplicity of these procedures makes them attractive for characterizing the molecular and biological properties of individual hematopoietic stem cells with unprecedented power and precision. © 2016 by John Wiley & Sons, Inc. PMID:27532815

  1. A Herbal Formula, Atofreellage, Ameliorates Atopic Dermatitis-Like Skin Lesions in an NC/Nga Mouse Model.

    Science.gov (United States)

    Kim, Won-Yong; Kim, Hyeong-Geug; Lee, Hye-Won; Lee, Jin-Seok; Im, Hwi-Jin; Kim, Hyo-Seon; Lee, Sung-Bae; Son, Chang-Gue

    2015-01-01

    We evaluated the anti-atopic dermatitis (AD) effect of Atofreellage (AF), a herbal formula composed of 10 medicinal plants. AD was induced on the dorsal skin areas of NC/Nga mice (male, seven weeks old) by daily application of 2,4-dinitrochlorobenzene (DNCB) for five weeks. After three weeks of DNCB application, 200 μL of AF (0, 25, 50 or 100 mg/mL) was applied to the skin lesions. Histological findings, blood cell populations, serum levels of immunoglobulin E (IgE), histamine, pro-inflammatory cytokines, and inflammatory signaling in the skin tissue, and T-helper cell type 2 (Th₂)-related cytokines in splenocytes were analyzed. Histopathological findings showed AF treatment notably attenuated the thickness of dorsal skin, and eosinophil infiltration. AF treatment (especially 100 mg/mL) also demonstrably ameliorated the blood cell population abnormalities, as the notable elevation of serum concentrations of IgE, histamine, TNF-α, IL-6 and IL-1β were remarkably normalized by AF treatment. Western blot analysis evidenced the apparent normalization of inflammatory signals (ERK, p38 MAP kinase, JNK, and NF-κB) in the skin tissue. Additionally, AF treatment notably attenuated the activation of Th₂-dominant cytokines (IL-13, IL-4, and IL-5) in Con A-treated splenocytes in an ex vivo assay. In conclusion, this study provides experimental evidence for the clinical relevance of Atofreellage. PMID:26712731

  2. Tumor initiating activities of various derivatives of benz(a)anthracene and 7, 12-dimethyl-benz(a)anthracene in mouse skin

    Energy Technology Data Exchange (ETDEWEB)

    Slaga, T.J.; Gleason, G.L.; DiGiovanni, J.; Berry, D.L.; Juchau, M.R.; Harvey, R.G.

    1978-01-01

    Current information indicates that polycyclic aromatic hydrocarbons (PAH) exert their toxic, mutagenic, and carcinogenic activities after they have been metabolically activated by target cells to reactive epoxides. The results obtained from IN VIVO and IN VITRO binding, mutagenicity, metabolism, and carcinogenicity studies have led to the conclusion that BP-7, 8-diol is a proximate carcinogenic metabolite of BP, and the BP-diol-epoxide is an ultimate carcinogenic metabolite of BP. Recent results concerning the strong carcinogenicity of BP-7..beta.., 8..cap alpha..-diol-9..cap alpha..,10..cap alpha..-epoxide in newborn mice and in mouse skin strongly indicate that it is the ultimate carcinogenic metabolite of BP. Since diol-epoxides may be responsible for the carcinogenicity of PAH other than BP, diols and diol-epoxides as well as other derivatives of PAH were tested for skin tumor-initiation in a two-stage system of tumorigenesis. In addition, since activation of methylated PAH may involve the side-chain methyl group, the skin tumor-initiating activity of various side-chain derivatives of methylated PA were determined. In this report, the skin tumor initiation of various derivatives of a nonmethylated PAH, BA as well as a methylated PAH, DMBA are compared. The data suggest that bay region diol-epoxides may be important in BA and DMBA carcinogenicity in mice which is supportive of the theory proposed by Jerina and co-workers which predicts that diol-epoxides in the bay region are the major determinants of PAH carcinogenicity.

  3. Anti-aging effect of adipose-derived stem cells in a mouse model of skin aging induced by D-galactose.

    Directory of Open Access Journals (Sweden)

    Shengchang Zhang

    Full Text Available INTRODUCTION: Glycation products accumulate during aging of slowly renewing tissue, including skin, and are suggested as an important mechanism underlying the skin aging process. Adipose-derived cells are widely used in the clinic to treat ischemic diseases and enhance wound healing. Interestingly, adipose-derived stem cells (ASCs are also effective in anti-aging therapy, although the mechanism underlying their effects remains unknown. The purpose of the present study was to examine the anti-aging effect of ASCs in a D-galactose-induced aging animal model and to clarify the underlying mechanism. MATERIALS AND METHODS: Six-week-old nude mice were subcutaneously injected with D-gal daily for 8 weeks. Two weeks after completion of treatment, mice were randomized to receive subcutaneous injections of 106 green fluorescent protein (GFP-expressing ASCs, aminoguanidine (AG or phosphate-buffered saline (PBS. Control mice received no treatment. We examined tissue histology and determined the activity of senescence-associated molecular markers such as superoxide dismutase (SOD and malondialdehyde (MDA. RESULTS: Transplanted ASCs were detectable for 14 days and their GFP signal disappeared at day 28 after injection. ASCs inhibited advanced glycation end product (AGE levels in our animal model as well as increased the SOD level and decreased the MDA level, all of which act to reverse the aging phenotype in a similar way to AG, an inhibitor of AGE formation. Furthermore, ASCs released angiogenic factors in vivo such as vascular endothelial growth factor, suggesting a skin trophic effect. CONCLUSIONS: These results demonstrate that ASCs may contribute to the regeneration of skin during aging. In addition, the data shows that ASCs provide a functional benefit by glycation suppression, antioxidation, and trophic effects in a mouse model of aging.

  4. 小鼠对量子点的透皮吸收和代谢%Transdermal Delivery Through in vivo Mouse Skin and Metabolic Path of Quantum Dots

    Institute of Scientific and Technical Information of China (English)

    唐蕾; 张春玲; 宋光明; 徐忠伟; 金迅

    2012-01-01

    皮肤是身体的最大器官,能够直接与含纳米材料的防晒霜、化妆品等接触,但是人们对纳米材料的皮肤渗透性却了解不多.本文研究了水溶性硫硒化镉(CdSeS)量子点纳米颗粒的皮肤渗透性和在体内的代谢情况.将雄性ICR鼠背部脱毛,在脱毛部位涂抹直径约为5nm、发光波长为620 nm的量子点0.32 nmol,然后检测皮肤和心、肝、脾、肺、肾中量子点沉积量随时间的变化情况.荧光显微像显示,量子点能够堆积在皮肤的表皮层中和真皮层的毛囊和腺体中,电感耦合等离子体质谱(inductively coupled plasma-mass spectrometry,ICP-MS)结果表明,透皮吸收的量子点能够沉积在器官中,并且肝和肾中沉积的量子点代谢缓慢,涂抹量子点5天之后,肾脏中残存的镉离子浓度仍超过14 ng/g.这些结果表明,量子点能够被小鼠透皮吸收,而且对肝和肾产生严重影响.%Skin is the largest organ of the body and is a potential route of exposure to sunscreens and cosmetics containing nanoparticles, but the permeability of the skin to these nanoparticles is unknown. In this paper, we studied the transdermal delivery capacity through mouse skin of water-soluble CdSeS quantum dots (QDs) and the deposition of these QDs in the body. QD solution was coated on the dorsal hairless skin of male ICR mice. Fluorescence microscope was used to observe the deposition of QDs in mouse skin and heart, liver, spleen, lung and kidney. Inductively coupled plasma-mass spectrometry (ICP-MS) was used to measure the mCd concentration to indicate the concentration of QDs in plasma and organs. The fluorescence images show that QDs can penetrate into the dermal layer and deposit in the organs through blood circulation. ICP-MS result indicates that QDs deposit seriously in liver and kidney, and they are difficult to clear. 111Cd concentration is still more than 14 ng/g in kidney after 5 days. These results suggest that QDs has in vivo

  5. Blockage of VIP during mouse embryogenesis modifies adult behavior and results in permanent changes in brain chemistry.

    Science.gov (United States)

    Hill, Joanna M; Hauser, Janet M; Sheppard, Lia M; Abebe, Daniel; Spivak-Pohis, Irit; Kushnir, Michal; Deitch, Iris; Gozes, Illana

    2007-01-01

    Vasoactive intestinal peptide (VIP) regulates growth and development during the early postimplantation period of mouse embryogenesis. Blockage of VIP with a VIP antagonist during this period results in growth restriction, microcephaly, and developmental delays. Similar treatment of neonatal rodents also causes developmental delays and impaired diurnal rhythms, and the adult brains of these animals exhibit neuronal dystrophy and increased VIP binding. These data suggest that blockage of VIP during the development of the nervous system can result in permanent changes to the brain. In the current study, pregnant mice were treated with a VIP antagonist during embryonic days 8 through 10. The adult male offspring were examined in tests of novelty, paired activity, and social recognition. Brain tissue was examined for several measures of chemistry and gene expression of VIP and related compounds. Glial cells from the cortex of treated newborn mice were plated with neurons and examined for VIP binding and their ability to enhance neuronal survival. Treated adult male mice exhibited increased anxiety-like behavior and deficits in social behavior. Brain tissue exhibited regionally specific changes in VIP chemistry and a trend toward increased gene expression of VIP and related compounds that reached statistical significance in the VIP receptor, VPAC-1, in the female cortex. When compared to control astrocytes, astrocytes from treated cerebral cortex produced further increases in neuronal survival with excess synaptic connections and reduced VIP binding. In conclusion, impaired VIP activity during mouse embryogenesis resulted in permanent changes to both adult brain chemistry/cell biology and behavior with aspects of autism-like social deficits. PMID:17726225

  6. Diminution of acute radiation reaction of mouse skin with low-intensity infrared laser/red diodes-emitted light

    International Nuclear Information System (INIS)

    Efficiency of the application of different regimes of laser treatment of radiation-induced skin reactions in mice feet is compared. Posterior limb feet of mice were exposed to acute X radiation at 30-36 Gy dose or fractionated radiation at 45 Gy dose. In the day of primary irradiation or different time later the feet were treated using magnetic infrared laser therapeutic MILTA-01 apparatus. Magnetic and light components of the MILTA-01 apparatus reduce the effect of radiation on mice skin corresponding two time decrease in X-radiation dose

  7. The expression characteristics and biological significance of bFGF, EGF,TGF-β isoforms and their receptors in skins from fetus and adult

    Institute of Scientific and Technical Information of China (English)

    Chen Wei; Fu Xiaobing; Sun Xiaoqing; Sun Tongzhu; Zhao Zhili; Sheng Zhiyong

    2002-01-01

    To observe the localization and expression characteristics of alpha-smooth muscle actin (AS-MA), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), transforming growth factor-β(TGF-β) isoforms, and their receptors in fetal and adult skins in order to explore their potential biological significance.Methods: The expression and the distribution of ASMA, bFGF, EGF, TGF-βisoforms, and their receptors were detected with immunohistochemistry and histopathology methods in 36 skin specimens. Among them, 30 specimens belonged to fetuses at different developmental stages and 6 were from adults. Results:Positive immunohistochemical signals of ASMA, bFGF, EGF, and TGF-βisoforms and their receptors could be found in fetal and postnatal skins.These factors were mainly distributed in the cytoplasm and extracellular matrix of epidermal cells, endothelial cells,hair follicle epithelial cells and some fibroblasts. Receptors of these factors were mostly located in the cellular membrane of the above mentioned cells, while protein particles of ASMA could be observed in myofibroblasts and sweat gland cells. Along with ascent in gestational age, the positive cellular rates of bFGF, EGF, TGF-βisoforms, their receptors, and ASMA in skin were elevated progressively. In skins specimens obtained from fetuses of late-trimester (29-31 week gestation) and adult, the positive rates of these proteins were significantly raised in comparison with skin of fetuses of early-trimester. Conclusion: The endogenous bFGF, EGF, three TGF-βisoforms and their receptors might be involved in the development of the skin in embryonic stage and in the cutaneous structure and function,and also wound healing in adult stage. The relative lack of these factors and their receptors might be one reason why the wound of fetus heal by regeneration rather than by scarring.

  8. Activation of CB1 inhibits NGF-induced sensitization of TRPV1 in adult mouse afferent neurons.

    Science.gov (United States)

    Wang, Z-Y; McDowell, T; Wang, P; Alvarez, R; Gomez, T; Bjorling, D E

    2014-09-26

    Transient receptor potential vanilloid 1 (TRPV1)-containing afferent neurons convey nociceptive signals and play an essential role in pain sensation. Exposure to nerve growth factor (NGF) rapidly increases TRPV1 activity (sensitization). In the present study, we investigated whether treatment with the selective cannabinoid receptor 1 (CB1) agonist arachidonyl-2'-chloroethylamide (ACEA) affects NGF-induced sensitization of TRPV1 in adult mouse dorsal root ganglion (DRG) afferent neurons. We found that CB1, NGF receptor tyrosine kinase A (trkA), and TRPV1 are present in cultured adult mouse small- to medium-sized afferent neurons and treatment with NGF (100ng/ml) for 30 min significantly increased the number of neurons that responded to capsaicin (as indicated by increased intracellular Ca(2 +) concentration). Pretreatment with the CB1 agonist ACEA (10nM) inhibited the NGF-induced response, and this effect of ACEA was reversed by a selective CB1 antagonist. Further, pretreatment with ACEA inhibited NGF-induced phosphorylation of AKT. Blocking PI3 kinase activity also attenuated the NGF-induced increase in the number of neurons that responded to capsaicin. Our results indicate that the analgesic effect of CB1 activation may in part be due to inhibition of NGF-induced sensitization of TRPV1 and also that the effect of CB1 activation is at least partly mediated by attenuation of NGF-induced increased PI3 signaling.

  9. Genetic manipulation of adult-born hippocampal neurons rescues memory in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Richetin, Kevin; Leclerc, Clémence; Toni, Nicolas; Gallopin, Thierry; Pech, Stéphane; Roybon, Laurent; Rampon, Claire

    2015-02-01

    In adult mammals, neural progenitors located in the dentate gyrus retain their ability to generate neurons and glia throughout lifetime. In rodents, increased production of new granule neurons is associated with improved memory capacities, while decreased hippocampal neurogenesis results in impaired memory performance in several memory tasks. In mouse models of Alzheimer's disease, neurogenesis is impaired and the granule neurons that are generated fail to integrate existing networks. Thus, enhancing neurogenesis should improve functional plasticity in the hippocampus and restore cognitive deficits in these mice. Here, we performed a screen of transcription factors that could potentially enhance adult hippocampal neurogenesis. We identified Neurod1 as a robust neuronal determinant with the capability to direct hippocampal progenitors towards an exclusive granule neuron fate. Importantly, Neurod1 also accelerated neuronal maturation and functional integration of new neurons during the period of their maturation when they contribute to memory processes. When tested in an APPxPS1 mouse model of Alzheimer's disease, directed expression of Neurod1 in cycling hippocampal progenitors conspicuously reduced dendritic spine density deficits on new hippocampal neurons, to the same level as that observed in healthy age-matched control animals. Remarkably, this population of highly connected new neurons was sufficient to restore spatial memory in these diseased mice. Collectively our findings demonstrate that endogenous neural stem cells of the diseased brain can be manipulated to become new neurons that could allow cognitive improvement. PMID:25518958

  10. Modifications of hippocampal circuits and early disruption of adult neurogenesis in the tg2576 mouse model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Alice Krezymon

    Full Text Available At advanced stages of Alzheimer's disease, cognitive dysfunction is accompanied by severe alterations of hippocampal circuits that may largely underlie memory impairments. However, it is likely that anatomical remodeling in the hippocampus may start long before any cognitive alteration is detected. Using the well-described Tg2576 mouse model of Alzheimer's disease that develops progressive age-dependent amyloidosis and cognitive deficits, we examined whether specific stages of the disease were associated with the expression of anatomical markers of hippocampal dysfunction. We found that these mice develop a complex pattern of changes in their dentate gyrus with aging. Those include aberrant expression of neuropeptide Y and reduced levels of calbindin, reflecting a profound remodeling of inhibitory and excitatory circuits in the dentate gyrus. Preceding these changes, we identified severe alterations of adult hippocampal neurogenesis in Tg2576 mice. We gathered converging data in Tg2576 mice at young age, indicating impaired maturation of new neurons that may compromise their functional integration into hippocampal circuits. Thus, disruption of adult hippocampal neurogenesis occurred before network remodeling in this mouse model and therefore may account as an early event in the etiology of Alzheimer's pathology. Ultimately, both events may constitute key components of hippocampal dysfunction and associated cognitive deficits occurring in Alzheimer's disease.

  11. A Novel Procedure for Rapid Imaging of Adult Mouse Brains with MicroCT Using Iodine-Based Contrast.

    Directory of Open Access Journals (Sweden)

    Ryan Anderson

    Full Text Available High-resolution Magnetic Resonance Imaging (MRI has been the primary modality for obtaining 3D cross-sectional anatomical information in animals for soft tissue, particularly brain. However, costs associated with MRI can be considerably high for large phenotypic screens for gross differences in the structure of the brain due to pathology and/or experimental manipulations. MicroCT (mCT, especially benchtop mCT, is becoming a common laboratory equipment with throughput rates equal or faster than any form of high-resolution MRI at lower costs. Here we explore adapting previously developed contrast based mCT to image adult mouse brains in-situ. We show that 2% weight per volume (w/v iodine-potassium iodide solution can be successfully used to image adult mouse brains within 48 hours post-mortem when a structural support matrix is used. We demonstrate that hydrogel can be effectively used as a perfusant which limits the tissue shrinkage due to iodine.

  12. Ultrastructural localization of the core protein of a basement membrane-specific chondroitin sulfate proteoglycan in adult rat skin

    DEFF Research Database (Denmark)

    McCarthy, K J; Horiguchi, Y; Couchman, J R;

    1990-01-01

    Basement membranes are complex extracellular matrices present at epithelial/mesenchymal interfaces of tissues. The dermal-epidermal junction has been shown to contain numerous components, some of the most well known being laminin, types IV and VII collagens, heparan sulfate proteoglycan, fibronec......Basement membranes are complex extracellular matrices present at epithelial/mesenchymal interfaces of tissues. The dermal-epidermal junction has been shown to contain numerous components, some of the most well known being laminin, types IV and VII collagens, heparan sulfate proteoglycan......, fibronectin, and entactin/nidogen. IN this paper we show, using core protein-specific antibodies, the presence of a newly described basement membrane-specific chondroitin sulfate proteoglycan at the epithelial/mesenchymal interface of adult rat skin. Ultrastructurally, this antigen was proven to reside...... primarily within the basal lamina, apparently concentrated in the lamina densa. In addition, some of the proteoglycan was also present beneath the lamina densa, associated with the reticular lamina collagen fibrils....

  13. Loss of hepatocyte-nuclear-factor-1alpha impacts on adult mouse intestinal epithelial cell growth and cell lineages differentiation.

    Directory of Open Access Journals (Sweden)

    Carine R Lussier

    Full Text Available BACKGROUND AND AIMS: Although Hnf1alpha is crucial for pancreas and liver functions, it is believed to play a limited functional role for intestinal epithelial functions. The aim of this study was to assess the consequences of abrogating Hnf1alpha on the maintenance of adult small intestinal epithelial functions. METHODOLOGY/PRINCIPAL FINDINGS: An Hnf1alpha knockout mouse model was used. Assessment of histological abnormalities, crypt epithelial cell proliferation, epithelial barrier, glucose transport and signalling pathways were measured in these animals. Changes in global gene expression were also analyzed. Mice lacking Hnf1alpha displayed increased crypt proliferation and intestinalomegaly as well as a disturbance of intestinal epithelial cell lineages production during adult life. This phenotype was associated with a decrease of the mucosal barrier function and lumen-to-blood glucose delivery. The mammalian target of rapamycin (mTOR signalling pathway was found to be overly activated in the small intestine of adult Hnf1alpha mutant mice. The intestinal epithelium of Hnf1alpha null mice displayed a reduction of the enteroendocrine cell population. An impact was also observed on proper Paneth cell differentiation with abnormalities in the granule exocytosis pathway. CONCLUSIONS/SIGNIFICANCE: Together, these results unravel a functional role for Hnf1alpha in regulating adult intestinal growth and sustaining the functions of intestinal epithelial cell lineages.

  14. Roughness threshold for cell attachment and proliferation on plasma micro-nanotextured polymeric surfaces: the case of primary human skin fibroblasts and mouse immortalized 3T3 fibroblasts

    Science.gov (United States)

    Bourkoula, A.; Constantoudis, V.; Kontziampasis, D.; Petrou, P. S.; Kakabakos, S. E.; Tserepi, A.; Gogolides, E.

    2016-08-01

    Poly(methyl methacrylate) surfaces have been micro-nanotextured in oxygen plasmas with increasing ion energy, leading to micro-nanotopography characterized by increased root mean square roughness, correlation length and fractal dimension. Primary human skin fibroblasts and mouse immortalized 3T3 fibroblasts were cultured on these surfaces and the number of adhering cells, their proliferation rate and morphology (cytoplasm and nucleus area) were evaluated as a function of roughness height, correlation length, and fractal dimension. A roughness threshold behavior was observed for both types of cells leading to dramatic cell number decrease above this threshold, which is almost similar for the two types of cells, despite their differences in size and stiffness. The results are discussed based on two theoretical models, which are reconciled and unified when the elastic moduli and the size of the cells are taken into account.

  15. Isolation and Culture of Adult Epithelial Stem Cells from Human Skin

    OpenAIRE

    Guo, Zhiru; Draheim, Kyle; Lyle, Stephen

    2011-01-01

    The homeostasis of all self-renewing tissues is dependent on adult stem cells. As undifferentiated stem cells undergo asymmetric divisions, they generate daughter cells that retain the stem cell phenotype and transit-amplifying cells (TA cells) that migrate from the stem cell niche, undergo rapid proliferation and terminally differentiate to repopulate the tissue.

  16. A lacZ reporter gene expression atlas for 313 adult KOMP mutant mouse lines

    OpenAIRE

    West, David B.; Pasumarthi, Ravi K.; Baridon, Brian; Djan, Esi; Trainor, Amanda; Stephen M Griffey; Engelhard, Eric K.; Rapp, Jared; LI, BOWEN; de Jong, Pieter J.; Lloyd, K. C. Kent

    2015-01-01

    Expression of the bacterial beta-galactosidase reporter gene (lacZ) in the vector used for the Knockout Mouse Project (KOMP) is driven by the endogenous promoter of the target gene. In tissues from KOMP mice, histochemical staining for LacZ enzyme activity can be used to determine gene expression patterns. With this technique, we have produced a comprehensive resource of gene expression using both whole mount (WM) and frozen section (FS) LacZ staining in 313 unique KOMP mutant mouse lines. Of...

  17. Myogenin Regulates Exercise Capacity and Skeletal Muscle Metabolism in the Adult Mouse

    OpenAIRE

    Flynn, Jesse M.; Eric Meadows; Marta Fiorotto; Klein, William H.

    2010-01-01

    Although skeletal muscle metabolism is a well-studied physiological process, little is known about how it is regulated at the transcriptional level. The myogenic transcription factor myogenin is required for skeletal muscle development during embryonic and fetal life, but myogenin's role in adult skeletal muscle is unclear. We sought to determine myogenin's function in adult muscle metabolism. A Myog conditional allele and Cre-ER transgene were used to delete Myog in adult mice. Mice were ana...

  18. MicroRNA-21a-5p Functions on the Regulation of Melanogenesis by Targeting Sox5 in Mouse Skin Melanocytes.

    Science.gov (United States)

    Wang, Pengchao; Zhao, Yuanyuan; Fan, Ruiwen; Chen, Tianzhi; Dong, Changsheng

    2016-01-01

    MicroRNAs (miRNAs) play an important role in regulating almost all biological processes. miRNAs bind to the 3' untranslated region (UTR) of mRNAs by sequence matching. In a previous study, we demonstrated that miR-21 was differently expressed in alpaca skin with different hair color. However, the molecular and cellular mechanisms for miR-21 to regulate the coat color are not yet completely understood. In this study, we transfected miR-21a-5p into mouse melanocytes and demonstrated its function on melanogenesis of miR-21a-5p by targeting Sox5, which inhibits melanogenesis in mouse melanocytes. The results suggested that miR-21a-5p targeted Sox5 gene based on the binding site in 3' UTR of Sox5 and overexpression of miR-21a-5p significantly down-regulated Sox5 mRNA and protein expression. Meanwhile, mRNA and protein expression of microphthalmia transcription factor (MITF) and Tyrosinase (TYR) were up-regulated, which subsequently make the melanin production in melanocytes increased. The results suggest that miR-21a-5p regulates melanogenesis via MITF by targeting Sox5. PMID:27347933

  19. MicroRNA-21a-5p Functions on the Regulation of Melanogenesis by Targeting Sox5 in Mouse Skin Melanocytes

    Directory of Open Access Journals (Sweden)

    Pengchao Wang

    2016-06-01

    Full Text Available MicroRNAs (miRNAs play an important role in regulating almost all biological processes. miRNAs bind to the 3′ untranslated region (UTR of mRNAs by sequence matching. In a previous study, we demonstrated that miR-21 was differently expressed in alpaca skin with different hair color. However, the molecular and cellular mechanisms for miR-21 to regulate the coat color are not yet completely understood. In this study, we transfected miR-21a-5p into mouse melanocytes and demonstrated its function on melanogenesis of miR-21a-5p by targeting Sox5, which inhibits melanogenesis in mouse melanocytes. The results suggested that miR-21a-5p targeted Sox5 gene based on the binding site in 3′ UTR of Sox5 and overexpression of miR-21a-5p significantly down-regulated Sox5 mRNA and protein expression. Meanwhile, mRNA and protein expression of microphthalmia transcription factor (MITF and Tyrosinase (TYR were up-regulated, which subsequently make the melanin production in melanocytes increased. The results suggest that miR-21a-5p regulates melanogenesis via MITF by targeting Sox5.

  20. Dual Effects of Bisphosphonates on Ectopic Skin and Vascular Soft Tissue Mineralization versus Bone Microarchitecture in a Mouse Model of Generalized Arterial Calcification of Infancy.

    Science.gov (United States)

    Li, Qiaoli; Kingman, Joshua; Sundberg, John P; Levine, Michael A; Uitto, Jouni

    2016-01-01

    Generalized arterial calcification of infancy is an intractable ectopic mineralization disorder caused by mutations in the ENPP1 gene, resulting in reduced plasma inorganic pyrophosphate (PPi) levels. We previously characterized the Enpp1(asj) mutant mouse as a model of generalized arterial calcification of infancy, and we have now explored the potential efficacy of bisphosphonates, nonhydrolyzable PPi analogs, in preventing ectopic mineralization in these mice. The mice were maintained on either basic diet (control) or diets containing etidronate or alendronate in three different concentrations (experimental). Considering low bioavailability of bisphosphonates when administered orally, subsequent studies tested the mice with subcutaneous injections of etidronate. The treatments were initiated at 4 weeks of age, and the degree of mineralization was assessed at 12 weeks of age by quantitation of calcium deposits in the muzzle skin containing dermal sheath of vibrissae and in aorta. We found that bisphosphonate treatments significantly reduced mineralization in skin and aorta. These changes in treated mice were accompanied with restoration of their bone microarchitecture, determined by microcomputed tomography. The inhibitory capacity of bisphosphonates, with mechanistic implications, was confirmed in a cell-based mineralization assay in vitro. Collectively, these results suggest that bisphosphonate treatment may be beneficial by a dual effect for preventing ectopic soft tissue mineralization while correcting decreased bone mineralization in generalized arterial calcification of infancy caused by ENPP1 mutations. PMID:26763447

  1. Designing a ridge filter based on a mouse foot skin reaction to spread out Bragg-peaks for carbon-ion radiotherapy

    International Nuclear Information System (INIS)

    Background and purpose: Carbon-ion radiotherapy uses spread-out Bragg peaks (SOBP) to produce uniform biological effects within a target volume. The relative biological effectiveness is determined by the in vitro cell kill after a single dose is employed to design the SOBP. A question remains as to whether biological effects for in vivo tissues after fractionated doses are also uniform within the SOBP. Material and methods: Mouse foot skin was irradiated with fractionated doses of carbon ions at various linear energy transfer (LET) values. A new ridge filter was designed based on alpha and beta values for each LET to cause moderate skin reaction, and was studied concerning its uniformity. Results: The reciprocal total doses of intermediate-LET carbon ions and of reference gamma rays linearly increased with an increase of a dose per fraction in Fe-plots. As the single total dose of higher LET run off linearity, data obtained from 2 to 6 fractions were used to design a new ridge filter. The physical dose distribution of the new ridge filter was almost identical to, and indistinguishable from, the ridge filter designed based on the in vitro cell kill. Conclusions: The LET dependence of alpha is a principle of the biological factor to be used for designing spread-out Bragg peaks of carbon-ion radiotherapy

  2. Autofluorescence imaging device for real-time detection and tracking of pathogenic bacteria in a mouse skin wound model: preclinical feasibility studies

    Science.gov (United States)

    Wu, Yichao Charlie; Kulbatski, Iris; Medeiros, Philip J.; Maeda, Azusa; Bu, Jiachuan; Xu, Lizhen; Chen, Yonghong; DaCosta, Ralph S.

    2014-08-01

    Bacterial infection significantly impedes wound healing. Clinical diagnosis of wound infections is subjective and suboptimal, in part because bacteria are invisible to the naked eye during clinical examination. Moreover, bacterial infection can be present in asymptomatic patients, leading to missed opportunities for diagnosis and treatment. We developed a prototype handheld autofluorescence (AF) imaging device (Portable Real-time Optical Detection, Identification and Guidance for Intervention-PRODIGI) to noninvasively visualize and measure bacterial load in wounds in real time. We conducted preclinical pilot studies in an established nude mouse skin wound model inoculated with bioluminescent Staphylococcus aureus bacteria. We tested the feasibility of longitudinal AF imaging for in vivo visualization of bacterial load in skin wounds, validated by bioluminescence imaging. We showed that bacteria (S. aureus), occult to standard examination, can be visualized in wounds using PRODIGI. We also detected quantitative changes in wound bacterial load over time based on the antibiotic treatment and the correlation of bacterial AF intensity with bacterial load. AF imaging of wounds offers a safe, noninvasive method for visualizing the presence, location, and extent of bacteria as well as measuring relative changes in bacterial load in wounds in real time.

  3. The Immune Response to Skin Trauma Is Dependent on the Etiology of Injury in a Mouse Model of Burn and Excision.

    Science.gov (United States)

    Valvis, Samantha M; Waithman, Jason; Wood, Fiona M; Fear, Mark W; Fear, Vanessa S

    2015-08-01

    Skin trauma has many different causes including incision, blunt force, and burn. All of these traumas trigger an immune response. However, it is currently unclear whether the immune response is specific to the etiology of the injury. This study was established to determine whether the immune response to excision and burn injury of equivalent extent was the same. Using a mouse model of a full-thickness 19 mm diameter excision or 19 mm diameter full-thickness burn injury, we examined the innate immune response at the level of serum cytokine induction, whole-blood lymphocyte populations, dendritic cell function/phenotype, and the ensuing adaptive immune responses of CD4 and CD8 T-cell populations. Strikingly, both the innate and adaptive immune system responses differed between the burn and excision injuries. Acute cytokine induction was faster and different in profile to that of excision injury, leading to changes in systemic monocyte and neutrophil levels. Differences in the immune profile between burn and excision were also noted up to day 84 post injury, suggesting that the etiology of injury leads to sustained changes in the response. This may in part underlie clinical observations of differences in patient morbidity and mortality in response to different skin injury types. PMID:25826422

  4. IgE Sensitization Patterns to Commonly Consumed Foods Determined by Skin Prick Test in Korean Adults.

    Science.gov (United States)

    Kim, Sung Ryeol; Park, Hye Jung; Park, Kyung Hee; Lee, Jae-Hyun; Park, Jung-Won

    2016-08-01

    Offending food allergens can vary with regional preferences in food consumption. In this study, we analysed sensitization rates to commonly consumed foods in Korean adults suspected of having food allergy. One hundred and thirty four subjects underwent a skin prick test (SPT) with 55 food allergens, of which 13 were made by our laboratory and the rest were commercially purchased. Of the 134 patients, 73 (54.5%) were sensitized to one or more food allergens. Sensitization to chrysalis was detected most frequently, at a rate of 25.4%. Sensitization rates to other food allergens were as follows: maize grain (13.4%), shrimp (11.9%), almond (11.1%), wheat flour (8.2%), lobster (8.2%), buckwheat (8.2%), mackerel (5.2%), pollack (5.2%), halibut (4.5%), peanut (4.5%), anchovy (4.4%), squid (3.7%), saury (3.0%), common eel (3.0%), yellow corvina (3.0%), hairtail (2.2%), octopus (2.2%), and others. In addition to well-known food allergens, sensitivity to mackerel, chrysalis, pollack, and halibut, which are popular foods in Korea, was observed at high rates in Korean adults. We suggest that the SPT panel for food allergy in Korea should include these allergens. PMID:27478328

  5. IgE Sensitization Patterns to Commonly Consumed Foods Determined by Skin Prick Test in Korean Adults

    Science.gov (United States)

    2016-01-01

    Offending food allergens can vary with regional preferences in food consumption. In this study, we analysed sensitization rates to commonly consumed foods in Korean adults suspected of having food allergy. One hundred and thirty four subjects underwent a skin prick test (SPT) with 55 food allergens, of which 13 were made by our laboratory and the rest were commercially purchased. Of the 134 patients, 73 (54.5%) were sensitized to one or more food allergens. Sensitization to chrysalis was detected most frequently, at a rate of 25.4%. Sensitization rates to other food allergens were as follows: maize grain (13.4%), shrimp (11.9%), almond (11.1%), wheat flour (8.2%), lobster (8.2%), buckwheat (8.2%), mackerel (5.2%), pollack (5.2%), halibut (4.5%), peanut (4.5%), anchovy (4.4%), squid (3.7%), saury (3.0%), common eel (3.0%), yellow corvina (3.0%), hairtail (2.2%), octopus (2.2%), and others. In addition to well-known food allergens, sensitivity to mackerel, chrysalis, pollack, and halibut, which are popular foods in Korea, was observed at high rates in Korean adults. We suggest that the SPT panel for food allergy in Korea should include these allergens. PMID:27478328

  6. Mouse skin tumor initiation-promotion and complete carcinogenesis bioassays: mechanisms and biological activities of emission samples.

    OpenAIRE

    Nesnow, S; Triplett, L L; Slaga, T J

    1983-01-01

    Extracts of soots obtained from various sources were applied to the skin of mice in an effort to identify carcinogens in these mixtures and to link these materials to the etiology of human cancer. Samples of coal chimney soot, coke oven materials, industrial carbon black, oil shale soot, and gasoline vehicle exhaust materials have been examined by this method. The studies reported here have been constructed to compare the carcinogenic and tumorigenic potency of extracts from various particula...

  7. Flat Mount Imaging of Mouse Skin and Its Application to the Analysis of Hair Follicle Patterning and Sensory Axon Morphology

    OpenAIRE

    Chang, Hao; Wang, Yanshu; Wu, Hao; Nathans, Jeremy

    2014-01-01

    Skin is a highly heterogeneous tissue. Intra-dermal structures include hair follicles, arrector pili muscles, epidermal specializations (such as Merkel cell clusters), sebaceous glands, nerves and nerve endings, and capillaries. The spatial arrangement of these structures is tightly controlled on a microscopic scale - as seen, for example, in the orderly arrangement of cell types within a single hair follicle - and on a macroscopic scale - as seen by the nearly identical orientations of thous...

  8. A highly enriched niche of precursor cells with neuronal and glial potential within the hair follicle dermal papilla of adult skin.

    Science.gov (United States)

    Hunt, David P J; Morris, Paul N; Sterling, Jane; Anderson, Jane A; Joannides, Alexis; Jahoda, Colin; Compston, Alastair; Chandran, Siddharthan

    2008-01-01

    Skin-derived precursor cells (SKPs) are multipotent neural crest-related stem cells that grow as self-renewing spheres and are capable of generating neurons and myelinating glial cells. SKPs are of clinical interest because they are accessible and potentially autologous. However, although spheres can be readily isolated from embryonic and neonatal skin, SKP frequency falls away sharply in adulthood, and primary sphere generation from adult human skin is more problematic. In addition, the culture-initiating cell population is undefined and heterogeneous, limiting experimental studies addressing important aspects of these cells such as the behavior of endogenous precursors in vivo and the molecular mechanisms of neural generation. Using a combined fate-mapping and microdissection approach, we identified and characterized a highly enriched niche of neural crest-derived sphere-forming cells within the dermal papilla of the hair follicle of adult skin. We demonstrated that the dermal papilla of the rodent vibrissal follicle is 1,000-fold enriched for sphere-forming neural crest-derived cells compared with whole facial skin. These "papillaspheres" share a phenotypic and developmental profile similar to that of SKPs, can be readily expanded in vitro, and are able to generate both neuronal and glial cells in response to appropriate cues. We demonstrate that papillaspheres can be efficiently generated and expanded from adult human facial skin by microdissection of a single hair follicle. This strategy of targeting a highly enriched niche of sphere-forming cells provides a novel and efficient method for generating neuronal and glial cells from an accessible adult somatic source that is both defined and minimally invasive.

  9. A highly enriched niche of precursor cells with neuronal and glial potential within the hair follicle dermal papilla of adult skin.

    Science.gov (United States)

    Hunt, David P J; Morris, Paul N; Sterling, Jane; Anderson, Jane A; Joannides, Alexis; Jahoda, Colin; Compston, Alastair; Chandran, Siddharthan

    2008-01-01

    Skin-derived precursor cells (SKPs) are multipotent neural crest-related stem cells that grow as self-renewing spheres and are capable of generating neurons and myelinating glial cells. SKPs are of clinical interest because they are accessible and potentially autologous. However, although spheres can be readily isolated from embryonic and neonatal skin, SKP frequency falls away sharply in adulthood, and primary sphere generation from adult human skin is more problematic. In addition, the culture-initiating cell population is undefined and heterogeneous, limiting experimental studies addressing important aspects of these cells such as the behavior of endogenous precursors in vivo and the molecular mechanisms of neural generation. Using a combined fate-mapping and microdissection approach, we identified and characterized a highly enriched niche of neural crest-derived sphere-forming cells within the dermal papilla of the hair follicle of adult skin. We demonstrated that the dermal papilla of the rodent vibrissal follicle is 1,000-fold enriched for sphere-forming neural crest-derived cells compared with whole facial skin. These "papillaspheres" share a phenotypic and developmental profile similar to that of SKPs, can be readily expanded in vitro, and are able to generate both neuronal and glial cells in response to appropriate cues. We demonstrate that papillaspheres can be efficiently generated and expanded from adult human facial skin by microdissection of a single hair follicle. This strategy of targeting a highly enriched niche of sphere-forming cells provides a novel and efficient method for generating neuronal and glial cells from an accessible adult somatic source that is both defined and minimally invasive. PMID:17901404

  10. An EPR method for estimating activity of antioxidants in mouse skin using an anthralin-derived radical model.

    Science.gov (United States)

    Kawai, Sayo; Matsumoto, Ken-Ichiro; Utsumi, Hideo

    2010-03-01

    Inhibitory effects of intravenously or orally administered antioxidants on the anthralin-derived radical generated in skin (mainly in the epidermis) of living mice by ultraviolet-A (UVA) irradiation were estimated. Anthralin was applied to the dorsal skin of living mice and the mice were then exposed to UVA. The EPR signal intensity in skin tissue strips obtained from mice after anthralin-UVA treatment was measured by an X-band EPR spectrometer. Several common antioxidants such as ascorbate, glutathione and Trolox (a vitamin E analogue) intravenously administered to mice reduced anthralin-derived radical generation. Trolox showed the most prolonged and powerful effect. Intravenous injection of a clinically used cerebral neuroprotective drug, Edarabone (Radicut), also showed depletion for the anthralin-derived radical. Oral administration of a commercialized nutritional supplement (a cocktail of 17 herbals and vitamins) also attenuated the anthralin-derived radical. The anthralin-UVA treatment model for antioxidant activity in the epidermis is a potentially feasible method to estimate activity of antioxidants in the body.

  11. CLARITY and PACT-based imaging of adult zebrafish and mouse for whole-animal analysis of infections.

    Science.gov (United States)

    Cronan, Mark R; Rosenberg, Allison F; Oehlers, Stefan H; Saelens, Joseph W; Sisk, Dana M; Jurcic Smith, Kristen L; Lee, Sunhee; Tobin, David M

    2015-12-01

    Visualization of infection and the associated host response has been challenging in adult vertebrates. Owing to their transparency, zebrafish larvae have been used to directly observe infection in vivo; however, such larvae have not yet developed a functional adaptive immune system. Cells involved in adaptive immunity mature later and have therefore been difficult to access optically in intact animals. Thus, the study of many aspects of vertebrate infection requires dissection of adult organs or ex vivo isolation of immune cells. Recently, CLARITY and PACT (passive clarity technique) methodologies have enabled clearing and direct visualization of dissected organs. Here, we show that these techniques can be applied to image host-pathogen interactions directly in whole animals. CLARITY and PACT-based clearing of whole adult zebrafish and Mycobacterium tuberculosis-infected mouse lungs enables imaging of mycobacterial granulomas deep within tissue to a depth of more than 1 mm. Using established transgenic lines, we were able to image normal and pathogenic structures and their surrounding host context at high resolution. We identified the three-dimensional organization of granuloma-associated angiogenesis, an important feature of mycobacterial infection, and characterized the induction of the cytokine tumor necrosis factor (TNF) within the granuloma using an established fluorescent reporter line. We observed heterogeneity in TNF induction within granuloma macrophages, consistent with an evolving view of the tuberculous granuloma as a non-uniform, heterogeneous structure. Broad application of this technique will enable new understanding of host-pathogen interactions in situ. PMID:26449262

  12. CLARITY and PACT-based imaging of adult zebrafish and mouse for whole-animal analysis of infections

    Directory of Open Access Journals (Sweden)

    Mark R. Cronan

    2015-12-01

    Full Text Available Visualization of infection and the associated host response has been challenging in adult vertebrates. Owing to their transparency, zebrafish larvae have been used to directly observe infection in vivo; however, such larvae have not yet developed a functional adaptive immune system. Cells involved in adaptive immunity mature later and have therefore been difficult to access optically in intact animals. Thus, the study of many aspects of vertebrate infection requires dissection of adult organs or ex vivo isolation of immune cells. Recently, CLARITY and PACT (passive clarity technique methodologies have enabled clearing and direct visualization of dissected organs. Here, we show that these techniques can be applied to image host-pathogen interactions directly in whole animals. CLARITY and PACT-based clearing of whole adult zebrafish and Mycobacterium tuberculosis-infected mouse lungs enables imaging of mycobacterial granulomas deep within tissue to a depth of more than 1 mm. Using established transgenic lines, we were able to image normal and pathogenic structures and their surrounding host context at high resolution. We identified the three-dimensional organization of granuloma-associated angiogenesis, an important feature of mycobacterial infection, and characterized the induction of the cytokine tumor necrosis factor (TNF within the granuloma using an established fluorescent reporter line. We observed heterogeneity in TNF induction within granuloma macrophages, consistent with an evolving view of the tuberculous granuloma as a non-uniform, heterogeneous structure. Broad application of this technique will enable new understanding of host-pathogen interactions in situ.

  13. Status epilepticus stimulates NDEL1 expression via the CREB/CRE pathway in the adult mouse brain.

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    Choi, Yun-Sik; Lee, Boyoung; Hansen, Katelin F; Aten, Sydney; Horning, Paul; Wheaton, Kelin L; Impey, Soren; Hoyt, Kari R; Obrietan, Karl

    2016-09-01

    Nuclear distribution element-like 1 (NDEL1/NUDEL) is a mammalian homolog of the Aspergillus nidulans nuclear distribution molecule NudE. NDEL1 plays a critical role in neuronal migration, neurite outgrowth and neuronal positioning during brain development; however within the adult central nervous system, limited information is available regarding NDEL1 expression and functions. Here, the goal was to examine inducible NDEL1 expression in the adult mouse forebrain. Immunolabeling revealed NDEL1 within the forebrain, including the cortex and hippocampus, as well as the midbrain and hypothalamus. Expression was principally localized to perikarya. Using a combination of immunolabeling and RNA seq profiling, we detected a marked and long-lasting upregulation of NDEL1 expression within the hippocampus following a pilocarpine-evoked repetitive seizure paradigm. Chromatin immunoprecipitation (ChIP) analysis identified a cAMP response element-binding protein (CREB) binding site within the CpG island proximal to the NDEL1 gene, and in vivo transgenic repression of CREB led to a marked downregulation of seizure-evoked NDEL1 expression. Together these data indicate that NDEL1 is inducibly expressed in the adult nervous system, and that signaling via the CREB/CRE transcriptional pathway is likely involved. The role of NDEL1 in neuronal migration and neurite outgrowth during development raises the interesting prospect that inducible NDEL1 in the mature nervous system could contribute to the well-characterized structural and functional plasticity resulting from repetitive seizure activity. PMID:27298008

  14. Low skin carotenoid concentration measured by resonance Raman spectroscopy is associated with metabolic syndrome in adults.

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    Holt, Edward W; Wei, Esther K; Bennett, Nancy; Zhang, Laura M

    2014-10-01

    Oxidative stress is increased in patients with metabolic syndrome (MS). Antioxidants, including carotenoids, are decreased in MS. We hypothesized that a low skin carotenoid score (SCS), calculated using resonance Raman spectroscopy, would correlate with the presence of MS. We retrospectively reviewed consecutive patients referred for dietary assessment between 2010 and 2012. For each patient, a nutrition history, medical history, and SCS were recorded. χ(2) and Student t test were used to determine factors associated with MS. Multivariate logistic regression was used to identify factors associated with MS. One hundred fifty-five patients were included. The mean age was 54.1 ± 13.1 years, and the mean body mass index was 28.3 ± 6.1 kg/m(2). Metabolic syndrome was present in 43.9% of patients. The mean SCS was 28 084 ± 14 006 Raman counts (RC), including 23 058 ± 9812 RC for patients with MS and 32 011 ± 15 514 RC for patients without MS (P = .0001). In a multivariate analysis, SCS less than 25 000 RC (odds ratio, 3.71; 95% confidence interval, 1.36-10.7; P = .01) was independently associated with MS. A higher number of MS components was associated with a progressively lower SCS (P = .004). In a consecutive sample of patients referred for dietary assessment, a noninvasively measured SCS was lower among patients with MS.

  15. Ex vivo differentiation of multipotent adult progenitor cells to skin epidermal cells

    Institute of Scientific and Technical Information of China (English)

    Ji Kaihong; Xiong Jun; Fan Lixing; Hu Kaimeng; Liu Houqi

    2009-01-01

    Objective: By establishing the indirect contact co-culture system, we studied the in vitro condition for MAPCs differentiating into epidermal cells and the transformation of MAPCs into epidermal cell phenotype. Methods: Cell culture insert membrane was used for substitute basal membrane and MAPCs, fibroblast cells (FCs) and mixture of MAPCs and epidermal cells and FCs were separately implanted into 2 sides of it. PKH26 was used to label cloned MAPCs; type Ⅳ collagen rapid adhering method was used to isolate and culture the skin epidermal cells from 1-day-old SD rat. Results: Part of the MAPCs transformed into cells expressing keratin in the presence of peripheral epithelia and FCs. Type Ⅳ collagen rapid adhering method successfully selected rats' epidermal stem cells. The mixture of the 2 kinds of cells or indirect culture might promote the differentiation through mesenchymal factors secreted by dermis FC. Conclusion: We were the first to have established the in vitro model of MAPCs differentiation into epidermal cells, in which MAPCs were transformed into epithelium-like cells.

  16. Fluorescent peptide biosensor for monitoring CDK4/cyclin D kinase activity in melanoma cell extracts, mouse xenografts and skin biopsies.

    Science.gov (United States)

    Prével, Camille; Pellerano, Morgan; González-Vera, Juan A; Henri, Pauline; Meunier, Laurent; Vollaire, Julien; Josserand, Véronique; Morris, May C

    2016-11-15

    Melanoma constitutes the most aggressive form of skin cancer, which further metastasizes into a deadly form of cancer. The p16(INK4a)-Cyclin D-CDK4/6-pRb pathway is dysregulated in 90% of melanomas. CDK4/Cyclin D kinase hyperactivation, associated with mutation of CDK4, amplification of Cyclin D or loss of p16(INK4a) leads to increased risk of developing melanoma. This kinase therefore constitutes a key biomarker in melanoma and an emerging pharmacological target, however there are no tools enabling direct detection or quantification of its activity. Here we report on the design and application of a fluorescent peptide biosensor to quantify CDK4 activity in melanoma cell extracts, skin biopsies and melanoma xenografts. This biosensor provides sensitive means of comparing CDK4 activity between different melanoma cell lines and further responds to CDK4 downregulation by siRNA or small-molecule inhibitors. By affording means of monitoring CDK4 hyperactivity consequent to cancer-associated molecular alterations in upstream signaling pathways that converge upon this kinase, this biosensor offers an alternative to immunological identification of melanoma-specific biomarkers, thereby constituting an attractive tool for diagnostic purposes, providing complementary functional information to histological analysis, of particular utility for detection of melanoma onset in precancerous lesions. This is indeed the first fluorescent peptide biosensor which has been successfully implemented to monitor kinase activity in skin samples and melanoma tumour xenografts. Moreover by enabling to monitor response to CDK4 inhibitors, this biosensor constitutes an attractive companion assay to identify compounds of therapeutic relevance for melanoma. PMID:27203461

  17. Fluorescent peptide biosensor for monitoring CDK4/cyclin D kinase activity in melanoma cell extracts, mouse xenografts and skin biopsies.

    Science.gov (United States)

    Prével, Camille; Pellerano, Morgan; González-Vera, Juan A; Henri, Pauline; Meunier, Laurent; Vollaire, Julien; Josserand, Véronique; Morris, May C

    2016-11-15

    Melanoma constitutes the most aggressive form of skin cancer, which further metastasizes into a deadly form of cancer. The p16(INK4a)-Cyclin D-CDK4/6-pRb pathway is dysregulated in 90% of melanomas. CDK4/Cyclin D kinase hyperactivation, associated with mutation of CDK4, amplification of Cyclin D or loss of p16(INK4a) leads to increased risk of developing melanoma. This kinase therefore constitutes a key biomarker in melanoma and an emerging pharmacological target, however there are no tools enabling direct detection or quantification of its activity. Here we report on the design and application of a fluorescent peptide biosensor to quantify CDK4 activity in melanoma cell extracts, skin biopsies and melanoma xenografts. This biosensor provides sensitive means of comparing CDK4 activity between different melanoma cell lines and further responds to CDK4 downregulation by siRNA or small-molecule inhibitors. By affording means of monitoring CDK4 hyperactivity consequent to cancer-associated molecular alterations in upstream signaling pathways that converge upon this kinase, this biosensor offers an alternative to immunological identification of melanoma-specific biomarkers, thereby constituting an attractive tool for diagnostic purposes, providing complementary functional information to histological analysis, of particular utility for detection of melanoma onset in precancerous lesions. This is indeed the first fluorescent peptide biosensor which has been successfully implemented to monitor kinase activity in skin samples and melanoma tumour xenografts. Moreover by enabling to monitor response to CDK4 inhibitors, this biosensor constitutes an attractive companion assay to identify compounds of therapeutic relevance for melanoma.

  18. Mutation spectrum in sunlight-exposed mouse skin epidermis: small but appreciable contribution of oxidative stress-mediated mutagenesis

    Energy Technology Data Exchange (ETDEWEB)

    Ikehata, Hironobu [Department of Cell Biology, Graduate School of Medicine, Tohoku University, Sendai 980-8575 (Japan)]. E-mail: ikehata@mail.tains.tohoku.ac.jp; Nakamura, Shingo [Department of Cell Biology, Graduate School of Medicine, Tohoku University, Sendai 980-8575 (Japan); Department of Radiobiology, Institute for Environmental Sciences, Aomori 039-3212 (Japan); Asamura, Takaaki [Department of Cell Biology, Graduate School of Medicine, Tohoku University, Sendai 980-8575 (Japan); Ono, Tetsuya [Department of Cell Biology, Graduate School of Medicine, Tohoku University, Sendai 980-8575 (Japan)

    2004-11-22

    We studied the mutations induced in skin by sunlight using transgenic Muta{sup TM} mice. Noon sunlight during summer at Sendai, Japan induced mutations efficiently in both epidermis and dermis. The mutant frequency (MF) in epidermis reached nearly 0.5% during the first 40 min irradiation but became saturated at this level with the appearance of skin inflammation after further irradiation. At the equivalent inflammatory dose, sunlight was twice as genotoxic as 313 nm-peak UVB. The 81 mutations detected in 80 lacZ transgene mutants isolated from the sunlight-exposed epidermis were dominated by C {yields} T transitions (89%), occurring exclusively at dipyrimidine sites, and also included a CC {yields} TT tandem substitution. Thus, the sunlight-induced mutation spectrum is highly UV-specific, quite similar to that induced by UVB but significantly different from that induced by UVA. Although oxidative damage-related C {yields} A transversions were detected only in five mutants (6%), their frequency was elevated to at least 15 times the background level, suggesting that the contribution of UVA-mediated oxidative stress is comparatively small but considerable. An analysis of bases adjacent to the mutated cytosines revealed that the sunlight-induced mutations prefer 5'-TC-3' dipyrimidine sites to 5'-CC-3' and 5'-CT-3'. The distribution of the frequent C {yields} T transition sites in the transgene was well associated with the CpG motif, which is known to be completely methylated in the gene, and quite similar to that induced by UVB rather than that by UVA. Thus, the UVB component contributes to the sunlight-induced mutations in the mammalian skin much more than the UVA component, whose influence through reactive oxygen species (ROS)-mediated mutagenesis is still appreciable.

  19. Photoprotective Potential of Penta-O-Galloyl-β-DGlucose by Targeting NF-κB and MAPK Signaling in UVB Radiation-Induced Human Dermal Fibroblasts and Mouse Skin.

    Science.gov (United States)

    Kim, Byung-Hak; Choi, Mi Sun; Lee, Hyun Gyu; Lee, Song-Hee; Noh, Kum Hee; Kwon, Sunho; Jeong, Ae Jin; Lee, Haeri; Yi, Eun Hee; Park, Jung Youl; Lee, Jintae; Joo, Eun Young; Ye, Sang-Kyu

    2015-11-01

    Exposure of the skin to ultraviolet radiation can cause skin damage with various pathological changes including inflammation. In the present study, we identified the skin-protective activity of 1,2,3,4,6-penta-O-galloyl-β-D-glucose (pentagalloyl glucose, PGG) in ultraviolet B (UVB) radiation-induced human dermal fibroblasts and mouse skin. PGG exhibited antioxidant activity with regard to intracellular reactive oxygen species (ROS) generation as well as ROS and reactive nitrogen species (RNS) scavenging. Furthermore, PGG exhibited anti-inflammatory activity, inhibiting the activation of nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling, resulting in inhibition of the expression of pro-inflammatory mediators. Topical application of PGG followed by chronic exposure to UVB radiation in the dorsal skin of hairless mice resulted in a significant decrease in the progression of inflammatory skin damages, leading to inhibited activation of NF-κB signaling and expression of pro-inflammatory mediators. The present study demonstrated that PGG protected from skin damage induced by UVB radiation, and thus, may be a potential candidate for the prevention of environmental stimuli-induced inflammatory skin damage.

  20. Distribution and densitometry mapping of L1-CAM Immunoreactivity in the adult mouse brain – light microscopic observation

    Directory of Open Access Journals (Sweden)

    Yamasaki Hironobu

    2003-04-01

    Full Text Available Abstract Background The importance of L1 expression in the matured brain is suggested by physiological and behavioral studies showing that L1 is related to hippocampal plasticity and fear conditioning. The distribution of L1 in mouse brain might provide a basis for understanding its role in the brain. Results We examined the overall distribution of L1 in the adult mouse brain by immunohistochemistry using two polyclonal antibodies against different epitopes for L1. Immunoreactive L1 was widely but unevenly distributed from the olfactory bulb to the upper cervical cord. The accumulation of immunoreactive L1 was greatest in a non-neuronal element of the major fibre bundles, i.e. the lateral olfactory tract, olfactory and temporal limb of the anterior commissure, corpus callosum, stria terminalis, globus pallidus, fornix, mammillothalamic tract, solitary tract, and spinal tract of the trigeminal nerve. High to highest levels of non-neuronal and neuronal L1 were found in the grey matter; i.e. the piriform and entorhinal cortices, hypothalamus, reticular part of the substantia nigra, periaqueductal grey, trigeminal spinal nucleus etc. High to moderate density of neuronal L1 was found in the olfactory bulb, layer V of the cerebral cortex, amygdala, pontine grey, superior colliculi, cerebellar cortex, solitary tract nucleus etc. Only low to lowest levels of neuronal L1 were found in the hippocampus, grey matter in the caudate-putamen, thalamus, cerebellar nuclei etc. Conclusion L1 is widely and unevenly distributed in the matured mouse brain, where immunoreactivity was present not only in neuronal elements; axons, synapses and cell soma, but also in non-neuronal elements.

  1. DNA microarray-based experimental strategy for trustworthy expression profiling of the hippocampal genes by astaxanthin supplementation in adult mouse

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    Jang Soo Yook

    2016-03-01

    Full Text Available Naturally occurring astaxantin (ASX is one of the noticeable carotenoid and dietary supplement, which has strong antioxidant and anti-inflammatory properties, and neuroprotective effects in the brain through crossing the blood–brain barrier. Specially, we are interested in the role of ASX as a brain food. Although ASX has been suggested to have potential benefit to the brain function, the underlying molecular mechanisms and events mediating such effect remain unknown. Here we examined molecular factors in the hippocampus of adult mouse fed ASX diets (0.1% and 0.5% doses using DNA microarray (Agilent 4 × 44 K whole mouse genome chip analysis. In this study, we described in detail our experimental workflow and protocol, and validated quality controls with the housekeeping gene expression (Gapdh and Beta-actin on the dye-swap based approach to advocate our microarray data, which have been uploaded to Gene Expression Omnibus (accession number GSE62197 as a gene resource for the scientific community. This data will also form an important basis for further detailed experiments and bioinformatics analysis with an aim to unravel the potential molecular pathways or mechanisms underlying the positive effects of ASX supplementation on the brain, in particular the hippocampus.

  2. The Phospholipase D2 Knock Out Mouse Has Ectopic Purkinje Cells and Suffers from Early Adult-Onset Anosmia

    Science.gov (United States)

    Zhang, Qifeng; Smethurst, Elizabeth; Segonds-Pichon, Anne; Schrewe, Heinrich; Wakelam, Michael J. O.

    2016-01-01

    Phospholipase D2 (PLD2) is an enzyme that produces phosphatidic acid (PA), a lipid messenger molecule involved in a number of cellular events including, through its membrane curvature properties, endocytosis. The PLD2 knock out (PLD2KO) mouse has been previously reported to be protected from insult in a model of Alzheimer's disease. We have further analysed a PLD2KO mouse using mass spectrophotometry of its lipids and found significant differences in PA species throughout its brain. We have examined the expression pattern of PLD2 which allowed us to define which region of the brain to analyse for defect, notably PLD2 was not detected in glial-rich regions. The expression pattern lead us to specifically examine the mitral cells of olfactory bulbs, the Cornus Amonis (CA) regions of the hippocampus and the Purkinje cells of the cerebellum. We find that the change to longer PA species correlates with subtle architectural defect in the cerebellum, exemplified by ectopic Purkinje cells and an adult-onset deficit of olfaction. These observations draw parallels to defects in the reelin heterozygote as well as the effect of high fat diet on olfaction. PMID:27658289

  3. Taurine in drinking water recovers learning and memory in the adult APP/PS1 mouse model of Alzheimer's disease.

    Science.gov (United States)

    Kim, Hye Yun; Kim, Hyunjin V; Yoon, Jin H; Kang, Bo Ram; Cho, Soo Min; Lee, Sejin; Kim, Ji Yoon; Kim, Joo Won; Cho, Yakdol; Woo, Jiwan; Kim, YoungSoo

    2014-12-12

    Alzheimer's disease (AD) is a lethal progressive neurological disorder affecting the memory. Recently, US Food and Drug Administration mitigated the standard for drug approval, allowing symptomatic drugs that only improve cognitive deficits to be allowed to accelerate on to clinical trials. Our study focuses on taurine, an endogenous amino acid found in high concentrations in humans. It has demonstrated neuroprotective properties against many forms of dementia. In this study, we assessed cognitively enhancing property of taurine in transgenic mouse model of AD. We orally administered taurine via drinking water to adult APP/PS1 transgenic mouse model for 6 weeks. Taurine treatment rescued cognitive deficits in APP/PS1 mice up to the age-matching wild-type mice in Y-maze and passive avoidance tests without modifying the behaviours of cognitively normal mice. In the cortex of APP/PS1 mice, taurine slightly decreased insoluble fraction of Aβ. While the exact mechanism of taurine in AD has not yet been ascertained, our results suggest that taurine can aid cognitive impairment and may inhibit Aβ-related damages.

  4. Wnt5a exhibits layer-specific expression in adult skin, is upregulated in psoriasis, and synergizes with type 1 interferon.

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    Malgorzata Romanowska

    Full Text Available BACKGROUND: Wnt5a is a member of the wingless-type patterning regulators important in pre-natal development. The expression and distribution of Wnt5a and its receptors frizzled (fzd 3 and fzd 5 in adult human skin have not been comprehensively studied to date. METHODOLOGY/PRINCIPAL FINDINGS: We here show that Wnt5a, fzd3, fzd5, as well as fzd6 are restricted to specific layers in normal epidermis, analogous to their zonal distribution in hair follicles, suggesting a role in adult skin differentiation. In line, Wnt5a and fzd5 are both overexpressed and re-distributed in the epidermis of psoriasis which involves disturbed keratinocyte differentiation. Functionally, Wnt5a lowers the concentration of IFN required to induce target genes, and increases the magnitude of IFN target gene induction, suggesting a molecular mechanism underlying IFN hypersensitivity in psoriasis. Finally, we identify nedd8 and the amyloid precursor APP, previously shown to be upregulated in psoriasis, as targets of synergistic IFNalpha/Wnt5a induction. CONCLUSIONS/SIGNIFICANCE: The present data (i suggest that Wnt5a regulates epidermal differentiation even in adult skin and (ii identify synergistic induction of type 1 IFN target genes as a novel mode of Wnt5a action. Targeting Wnt5a in the skin may reduce IFN hypersensitivity and be of therapeutical value.

  5. The excimer lamp induces cutaneous nerve degeneration and reduces scratching in a dry-skin mouse model.

    Science.gov (United States)

    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.

  6. Identification of an mtDNA mutation hot spot in UV-induced mouse skin tumors producing altered cellular biochemistry.

    Science.gov (United States)

    Jandova, Jana; Eshaghian, Alex; Shi, Mingjian; Li, Meiling; King, Lloyd E; Janda, Jaroslav; Sligh, James E

    2012-02-01

    There is increasing awareness of the role of mtDNA alterations in the development of cancer, as mtDNA point mutations are found at high frequency in a variety of human tumors. To determine the biological effects of mtDNA mutations in UV-induced skin tumors, hairless mice were irradiated to produce tumors, and the tumor mtDNAs were screened for single-nucleotide changes using temperature gradient capillary electrophoresis (TGCE), followed by direct sequencing. A mutation hot spot (9821insA) in the mitochondrially encoded tRNA arginine (mt-Tr) locus (tRNA(Arg)) was discovered in approximately one-third of premalignant and malignant skin tumors. To determine the functional relevance of this particular mutation in vitro, cybrid cell lines containing different mt-Tr (tRNA(Arg)) alleles were generated. The resulting cybrid cell lines contained the same nuclear genotype and differed only in their mtDNAs. The biochemical analysis of the cybrids revealed that the mutant haplotype is associated with diminished levels of complex I protein (CI), resulting in lower levels of baseline oxygen consumption and lower cellular adenosine triphosphate (ATP) production. We hypothesize that this specific mtDNA mutation alters cellular biochemistry, supporting the development of keratinocyte neoplasia.

  7. The excimer lamp induces cutaneous nerve degeneration and reduces scratching in a dry-skin mouse model.

    Science.gov (United States)

    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. PMID:24940652

  8. PPARβ/δ and PPARγ maintain undifferentiated phenotypes of mouse adult neural precursor cells from the subventricular zone.

    Science.gov (United States)

    Bernal, Carolina; Araya, Claudia; Palma, Verónica; Bronfman, Miguel

    2015-01-01

    The subventricular zone (SVZ) is one of the main niches of neural stem cells in the adult mammalian brain. Stem and precursor cells in this region are the source for neurogenesis and oligodendrogesis, mainly in the olfactory bulb and corpus callosum, respectively. The identification of the molecular components regulating the decision of these cells to differentiate or maintain an undifferentiated state is important in order to understand the modulation of neurogenic processes in physiological and pathological conditions. PPARs are a group of transcription factors, activated by lipid ligands, with important functions in cellular differentiation and proliferation in several tissues. In this work, we demonstrate that mouse adult neural precursor cells (NPCs), in situ and in vitro, express PPARβ/δ and PPARγ. Pharmacological activation of both PPARs isoforms induces proliferation and maintenance of the undifferentiated phenotype. Congruently, inhibition of PPARβ/δ and PPARγ results in a decrease of proliferation and loss of the undifferentiated phenotype. Interestingly, PPARγ regulates the level of EGFR in adult NPCs, concurrent with it is function described in embryonic NPCs. Furthermore, we describe for the first time that PPARβ/δ regulates SOX2 level in adult NPCs, probably through a direct transcriptional regulation, as we identified two putative PPAR response elements in the promoter region of Sox2. EGFR and SOX2 are key players in neural stem/precursor cells self-renewal. Finally, rosiglitazone, a PPARγ ligand, increases PPARβ/δ level, suggesting a possible cooperation between these two PPARs in the control of cell fate behavior. Our work contributes to the understanding of the molecular mechanisms associated to neural cell fate decision and places PPARβ/δ and PPARγ as interesting new targets of modulation of mammalian brain homeostasis. PMID:25852474

  9. Crowdsourced Data Indicate Widespread Multidrug Resistance in Skin Flora of Healthy Young Adults

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    Scott Freeman

    2015-10-01

    Full Text Available In a laboratory exercise for undergraduate biology majors, students plated bacteria from swabs of their facial skin under conditions that selected for coagulase-negative Staphylococcus; added disks containing the antibiotics penicillin, oxacillin, tetracycline, and erythromycin; and measured zones of inhibition. Students also recorded demographic and lifestyle variables and merged this information with similar data collected from 9,000 other students who had contributed to the database from 2003 to 2011. Minimum inhibitory concentration (MIC testing performed at the Harborview Medical Center Microbiology Laboratory (Seattle, WA indicated a high degree of accuracy for student-generated data; species identification with a matrix-assisted laser desorption ionization (MALDI Biotyper revealed that over 88% of the cells analyzed by students were S. epidermidis or S. capitus. The overall frequency of resistant cells was high, ranging from 13.2% of sampled bacteria resistant to oxacillin to 61.7% resistant to penicillin. Stepwise logistic regressions suggested that recent antibiotic use was strongly associated with resistance to three of the four antibiotics tested (p = 0.0003 for penicillin, p << 0.0001 for erythromycin and tetracycline, and that age, gender, use of acne medication, use of antibacterial soaps, or makeup use were associated with resistance to at least one of the four antibiotics. Furthermore, drug resistance to one antibiotic was closely linked to resistance to the other three antibiotics in every case (all p values << 0.0001, suggesting the involvement of multidrug–resistant strains. The data reported here suggest that citizen science could not only provide an important educational experience for undergraduates, but potentially play a role in efforts to expand antibiotic resistance (ABR surveillance.

  10. Crowdsourced Data Indicate Widespread Multidrug Resistance in Skin Flora of Healthy Young Adults.

    Science.gov (United States)

    Freeman, Scott; Okoroafor, Nnadozie O; Gast, Christopher M; Koval, Mikhail; Nowowiejski, David; O'Connor, Eileen; Harrington, Robert D; Parks, John W; Fang, Ferric C

    2016-03-01

    In a laboratory exercise for undergraduate biology majors, students plated bacteria from swabs of their facial skin under conditions that selected for coagulase-negative Staphylococcus; added disks containing the antibiotics penicillin, oxacillin, tetracycline, and erythromycin; and measured zones of inhibition. Students also recorded demographic and lifestyle variables and merged this information with similar data collected from 9,000 other students who had contributed to the database from 2003 to 2011. Minimum inhibitory concentration (MIC) testing performed at the Harborview Medical Center Microbiology Laboratory (Seattle, WA) indicated a high degree of accuracy for student-generated data; species identification with a matrix-assisted laser desorption ionization (MALDI) Biotyper revealed that over 88% of the cells analyzed by students were S. epidermidis or S. capitus. The overall frequency of resistant cells was high, ranging from 13.2% of sampled bacteria resistant to oxacillin to 61.7% resistant to penicillin. Stepwise logistic regressions suggested that recent antibiotic use was strongly associated with resistance to three of the four antibiotics tested (p = 0.0003 for penicillin, p antibacterial soaps, or makeup use were associated with resistance to at least one of the four antibiotics. Furthermore, drug resistance to one antibiotic was closely linked to resistance to the other three antibiotics in every case (all p values < 0.0001), suggesting the involvement of multidrug-resistant strains. The data reported here suggest that citizen science could not only provide an important educational experience for undergraduates, but potentially play a role in efforts to expand antibiotic resistance (ABR) surveillance. PMID:27047615

  11. The heparan sulphate deficient Hspg2 exon 3 null mouse displays reduced deposition of TGF-β1 in skin compared to C57BL/6 wild type mice.

    Science.gov (United States)

    Shu, Cindy; Smith, Susan M; Melrose, James

    2016-06-01

    This was an observational study where we examined the role of perlecan HS on the deposition of TGF-β1 in C57BL/6 and Hspg2(∆3-/∆3-) perlecan exon 3 null mouse skin. Despite its obvious importance in skin repair and tissue homeostasis no definitive studies have immunolocalised TGF-β1 in skin in WT or Hspg2(∆3-/∆3-) perlecan exon 3 null mice. Vertical parasagittal murine dorsal skin from 3, 6 and 12 week old C57BL/6 and Hspg2(∆3-/∆3-) mice were fixed in neutral buffered formalin, paraffin embedded and 4 μm sections stained with Mayers haematoxylin and eosin (H & E). TGF-β1 was immunolocalised using a rabbit polyclonal antibody, heat retrieval and the Envision NovaRED detection system. Immunolocalisation of TGF-β1 differed markedly in C57BL/6 and Hspg2(∆3-/∆3-) mouse skin, ablation of exon 3 of Hspg2 resulted in a very severe reduction in the deposition of TGF-β1 in skin 3-12 weeks postnatally. The reduced deposition of TGF-β1 observed in the present study would be expected to impact detrimentally on the remodelling and healing capacity of skin in mutant mice compounding on the poor wound-healing properties already reported for perlecan exon 3 null mice due to an inability to signal with FGF-2 and promote angiogenic repair processes. TGF-β1 also has cell mediated effects in tissue homeostasis and matrix stabilisation a reduction in TGF-β1 deposition would therefore be expected to detrimentally impact on skin homeostasis in the perlecan mutant mice.

  12. Myogenin regulates exercise capacity and skeletal muscle metabolism in the adult mouse.

    Directory of Open Access Journals (Sweden)

    Jesse M Flynn

    Full Text Available Although skeletal muscle metabolism is a well-studied physiological process, little is known about how it is regulated at the transcriptional level. The myogenic transcription factor myogenin is required for skeletal muscle development during embryonic and fetal life, but myogenin's role in adult skeletal muscle is unclear. We sought to determine myogenin's function in adult muscle metabolism. A Myog conditional allele and Cre-ER transgene were used to delete Myog in adult mice. Mice were analyzed for exercise capacity by involuntary treadmill running. To assess oxidative and glycolytic metabolism, we performed indirect calorimetry, monitored blood glucose and lactate levels, and performed histochemical analyses on muscle fibers. Surprisingly, we found that Myog-deleted mice performed significantly better than controls in high- and low-intensity treadmill running. This enhanced exercise capacity was due to more efficient oxidative metabolism during low- and high-intensity exercise and more efficient glycolytic metabolism during high-intensity exercise. Furthermore, Myog-deleted mice had an enhanced response to long-term voluntary exercise training on running wheels. We identified several candidate genes whose expression was altered in exercise-stressed muscle of mice lacking myogenin. The results suggest that myogenin plays a critical role as a high-level transcriptional regulator to control the energy balance between aerobic and anaerobic metabolism in adult skeletal muscle.

  13. Cardiomyocyte proliferation and progenitor cell recruitment underlie therapeutic regeneration after myocardial infarction in the adult mouse heart.

    Science.gov (United States)

    Malliaras, Konstantinos; Zhang, Yiqiang; Seinfeld, Jeffrey; Galang, Giselle; Tseliou, Eleni; Cheng, Ke; Sun, Baiming; Aminzadeh, Mohammad; Marbán, Eduardo

    2013-02-01

    Cardiosphere-derived cells (CDCs) have been shown to regenerate infarcted myocardium in patients after myocardial infarction (MI). However, whether the cells of the newly formed myocardium originate from the proliferation of adult cardiomyocytes or from the differentiation of endogenous stem cells remains unknown. Using genetic fate mapping to mark resident myocytes in combination with long-term BrdU pulsing, we investigated the origins of postnatal cardiomyogenesis in the normal, infarcted and cell-treated adult mammalian heart. In the normal mouse heart, cardiomyocyte turnover occurs predominantly through proliferation of resident cardiomyocytes at a rate of ∼1.3-4%/year. After MI, new cardiomyocytes arise from both progenitors as well as pre-existing cardiomyocytes. Transplantation of CDCs upregulates host cardiomyocyte cycling and recruitment of endogenous progenitors, while boosting heart function and increasing viable myocardium. The observed phenomena cannot be explained by cardiomyocyte polyploidization, bi/multinucleation, cell fusion or DNA repair. Thus, CDCs induce myocardial regeneration by differentially upregulating two mechanisms of endogenous cell proliferation.

  14. Expression of tryptophan 2,3-dioxygenase in mature granule cells of the adult mouse dentate gyrus

    Directory of Open Access Journals (Sweden)

    Ohira, Koji

    2010-09-01

    Full Text Available Abstract New granule cells are continuously generated in the dentate gyrus of the adult hippocampus. During granule cell maturation, the mechanisms that differentiate new cells not only describe the degree of cell differentiation, but also crucially regulate the progression of cell differentiation. Here, we describe a gene, tryptophan 2,3-dioxygenase (TDO, whose expression distinguishes stem cells from more differentiated cells among the granule cells of the adult mouse dentate gyrus. The use of markers for proliferation, neural progenitors, and immature and mature granule cells indicated that TDO was expressed in mature cells and in some immature cells. In mice heterozygous for the alpha-isoform of calcium/calmodulin-dependent protein kinase II, in which dentate gyrus granule cells fail to mature normally, TDO immunoreactivity was substantially downregulated in the dentate gyrus granule cells. Moreover, a 5-bromo-2'-deoxyuridine labeling experiment revealed that new neurons began to express TDO between 2 and 4 wk after the neurons were generated, when the axons and dendrites of the granule cells developed and synaptogenesis occurred. These findings indicate that TDO might be required at a late-stage of granule cell development, such as during axonal and dendritic growth, synaptogenesis and its maturation.

  15. The developmental regulator Pax6 is essential for maintenance of islet cell function in the adult mouse pancreas.

    Directory of Open Access Journals (Sweden)

    Alan W Hart

    Full Text Available The transcription factor Pax6 is a developmental regulator with a crucial role in development of the eye, brain, and olfactory system. Pax6 is also required for correct development of the endocrine pancreas and specification of hormone producing endocrine cell types. Glucagon-producing cells are almost completely lost in Pax6-null embryos, and insulin-expressing beta and somatostatin-expressing delta cells are reduced. While the developmental role of Pax6 is well-established, investigation of a further role for Pax6 in the maintenance of adult pancreatic function is normally precluded due to neonatal lethality of Pax6-null mice. Here a tamoxifen-inducible ubiquitous Cre transgene was used to inactivate Pax6 at 6 months of age in a conditional mouse model to assess the effect of losing Pax6 function in adulthood. The effect on glucose homeostasis and the expression of key islet cell markers was measured. Homozygous Pax6 deletion mice, but not controls, presented with all the symptoms of classical diabetes leading to severe weight loss requiring termination of the experiment five weeks after first tamoxifen administration. Immunohistochemical analysis of the pancreata revealed almost complete loss of Pax6 and much reduced expression of insulin, glucagon, and somatostatin. Several other markers of islet cell function were also affected. Notably, strong upregulation in the number of ghrelin-expressing endocrine cells was observed. These findings demonstrate that Pax6 is essential for adult maintenance of glucose homeostasis and function of the endocrine pancreas.

  16. Expression of the Argonaute protein PiwiL2 and piRNAs in adult mouse mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Qiuling; Ma, Qi; Shehadeh, Lina A.; Wilson, Amber; Xia, Linghui; Yu, Hong [Department of Molecular and Cellular Pharmacology, Vascular Biology Institute, University of Miami Miller School of Medicine, Miami, FL 33136 (United States); Webster, Keith A., E-mail: kwebster@med.miami.edu [Department of Molecular and Cellular Pharmacology, Vascular Biology Institute, University of Miami Miller School of Medicine, Miami, FL 33136 (United States)

    2010-06-11

    Piwi (P-element-induced wimpy testis) first discovered in Drosophila is a member of the Argonaute family of micro-RNA binding proteins with essential roles in germ-cell development. The murine homologue of PiwiL2, also known as Mili is selectively expressed in the testes, and mice bearing targeted mutations of the PiwiL2 gene are male-sterile. PiwiL2 proteins are thought to protect the germ line genome by suppressing retrotransposons, stabilizing heterochromatin structure, and regulating target genes during meiosis and mitosis. Here, we report that PiwiL2 and associated piRNAs (piRs) may play similar roles in adult mouse mesenchymal stem cells. We found that PiwiL2 is expressed in the cytoplasm of metaphase mesenchymal stem cells from the bone marrow of adult and aged mice. Knockdown of PiwiL2 with a specific siRNA enhanced cell proliferation, significantly increased the number of cells in G1/S and G2/M cell cycle phases and was associated with increased expression of cell cycle genes CCND1, CDK8, microtubule regulation genes, and decreased expression of tumor suppressors Cables 1, LATS, and Cxxc4. The results suggest broader roles for Piwi in genome surveillance beyond the germ line and a possible role in regulating the cell cycle of mesenchymal stem cells.

  17. Vitamin D for combination photodynamic therapy of skin cancer in individuals with vitamin D deficiency: Insights from a preclinical study in a mouse model of squamous cell carcinoma

    Science.gov (United States)

    Anand, Sanjay; Thomas, Erik; Hasan, Tayyaba; Maytin, Edward V.

    2016-03-01

    Combination photodynamic therapy (cPDT) in which vitamin D (VD) is given prior to aminolevulinate, a precursor (pro-drug) for protoporphyrin IX (PpIX), is an approach developed in our laboratory. We previously showed that 1α,25- dihydroxyvitamin D3 (calcitriol), given prior to PDT, enhances accumulation of PpIX and improves cell death post-PDT in a mouse skin cancer model. However, since calcitriol poses a risk for hypercalcemia, we replaced systemic calcitriol with oral cholecalciferol (D3), administered as a high (tenfold, "10K") diet over a ten-day period. Here, we ask whether VD deficiency might alter the response to cPDT. Nude mice were fed a VD-deficient diet for at least 4 weeks ("deficient"); controls were fed a normal 1,000 IU/kg diet ("1K"). Human A431 cells were implanted subcutaneously and mice were switched to the 10K diet or continued on their baseline diets (controls). In other experiments, mice received a human equivalent dose of 50,000 IU D3 by oral gavage, to simulate administration of a single, high-dose VD pill. At various times, tumors were harvested and serum was collected to measure levels of VD metabolic intermediates. A significant increase in PpIX levels and in the expression of differentiation and proliferation markers in tumor tissue was observed after VD supplementation of both the deficient and 1K mice. Further results describing mechanistic details of PpIX enhancement through alteration of heme- and VD-metabolic enzyme levels will be presented. Based on these results, a clinical study using oral vitamin D prior to PDT for human skin cancer should be performed.

  18. [Adult-onset Hartnup disease presenting with neuropsychiatric symptoms but without skin lesions].

    Science.gov (United States)

    Mori, E; Yamadori, A; Tsutsumi, A; Kyotani, Y

    1989-06-01

    Hartnup disease is an inborn abnormality of renal and intestinal transport involving the neutral amino acids. Intermittent pellagra-like rash, attacks of cerebellar ataxia and psychiatric disturbance are characteristic symptoms of this disease. We described here a patient with adult-onset Hartnup disease who presented unique neuropsychiatric symptoms but no dermatologic symptoms, and reported features of amino acids transport in this patient and his family. The patient, a man aged 37 years, was referred to us because of lasting daytime bruxism. He is the second child of healthy parents who are first cousin; his elder brother who has been mentally retarded became bed-ridden and died at 32 years of age. His younger brother is completely healthy. Although the patient's development in infancy has been slightly retarded, he completed compulsory 9-year education. At 29 years of age, he experienced episodes of diplopia, ataxic gait and insomnia, and at 33 years of age, of transient stupor. There had been no history of photosensitivity or dermatitis. On neurological examination, there were trunkal ataxia, increased muscular tone and decreased mental activity besides bruxism. These symptoms remained unchanged despite of several medications including trihexyphenidyl, diazepam, halloperidol, tiapride and sulpiride. Two months later, the patient became stuporous; bruxism and hypertonicity became exaggerated. Myerson's sign, sucking reflex and grasp reflex in both hand appeared. There was no dermal lesion. A cranial computed tomography revealed a small calcification in the right frontal subcortical region and a single photon emission tomography indicated possible bifrontal hypoperfusion. Electroencephalograms demonstrated non-specific slowing. Somatosensory evoked potentials and nerve conduction velocities were normal. There were constant indicanuria and amino-aciduria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2582682

  19. Variable partial unilateral ureteral obstruction and its release in the neonatal and adult mouse.

    Science.gov (United States)

    Thornhill, Barbara A; Chevalier, Robert L

    2012-01-01

    Obstructive nephropathy is the most important cause of renal failure in children. Unilateral ureteral obstruction (UUO) in the neonatal mouse provides a useful model to investigate the response of the developing kidney to urine flow obstruction. Creation of reversible variable partial UUO (compared to complete UUO) more closely approximates congenital lesions, and permits the study of recovery following release of the obstruction. Implementation of this technique requires the appropriate optical, surgical, and anesthetic equipment, as well as adaptations appropriate to the very small animals undergoing surgical procedures. Care of the pups must include minimizing trauma to delicate tissues, close monitoring of anesthesia and body temperature, and ensuring acceptance of the pups by the mother. It is important to document the severity and patency of the partial UUO by ureteral measurement and pelvic injection of India ink. Finally, removal of kidneys for histologic examination should be accomplished with gentle handling and processing. PMID:22639278

  20. Genistein exposure inhibits growth and alters steroidogenesis in adult mouse antral follicles.

    Science.gov (United States)

    Patel, Shreya; Peretz, Jackye; Pan, Yuan-Xiang; Helferich, William G; Flaws, Jodi A

    2016-02-15

    Genistein is a naturally occurring isoflavone phytoestrogen commonly found in plant products such as soybeans, lentils, and chickpeas. Genistein, like other phytoestrogens, has the potential to mimic, enhance, or impair the estradiol biosynthesis pathway, thereby potentially altering ovarian follicle growth. Previous studies have inconsistently indicated that genistein exposure may alter granulosa cell proliferation and hormone production, but no studies have examined the effects of genistein on intact antral follicles. Thus, this study was designed to test the hypothesis that genistein exposure inhibits follicle growth and steroidogenesis in intact antral follicles. To test this hypothesis, antral follicles isolated from CD-1 mice were cultured with vehicle (dimethyl sulfoxide; DMSO) or genistein (6.0 and 36μM) for 18-96h. Every 24h, follicle diameters were measured to assess growth. At the end of each culture period, the media were pooled to measure hormone levels, and the cultured follicles were collected to measure expression of cell cycle regulators and steroidogenic enzymes. The results indicate that genistein (36μM) inhibits growth of mouse antral follicles. Additionally, genistein (6.0 and 36μM) increases progesterone, testosterone, and dehydroepiandrosterone (DHEA) levels, but decreases estrone and estradiol levels. The results also indicate that genistein alters the expression of steroidogenic enzymes at 24, 72 and 96h, and the expression of cell cycle regulators at 18h. These data indicate that genistein exposure inhibits antral follicle growth by inhibiting the cell cycle, alters sex steroid hormone levels, and dysregulates steroidogenic enzymes in cultured mouse antral follicles. PMID:26792615

  1. Roles of Wnt Signaling in the Neurogenic Niche of the Adult Mouse Ventricular-Subventricular Zone.

    Science.gov (United States)

    Hirota, Yuki; Sawada, Masato; Huang, Shih-Hui; Ogino, Takashi; Ohata, Shinya; Kubo, Akiharu; Sawamoto, Kazunobu

    2016-02-01

    In many animal species, the production of new neurons (neurogenesis) occurs throughout life, in a specialized germinal region called the ventricular-subventricular zone (V-SVZ). In this region, neural stem cells undergo self-renewal and generate neural progenitor cells and new neurons. In the olfactory system, the new neurons migrate rostrally toward the olfactory bulb, where they differentiate into mature interneurons. V-SVZ-derived new neurons can also migrate toward sites of brain injury, where they contribute to neural regeneration. Recent studies indicate that two major branches of the Wnt signaling pathway, the Wnt/β-catenin and Wnt/planar cell polarity pathways, play essential roles in various facets of adult neurogenesis. Here, we review the Wnt signaling-mediated regulation of adult neurogenesis in the V-SVZ under physiological and pathological conditions. PMID:26572545

  2. Functional correction of adult mdx mouse muscle using gutted adenoviral vectors expressing full-length dystrophin

    OpenAIRE

    DelloRusso, Christiana; Scott, Jeannine M.; Hartigan-O'Connor, Dennis; Salvatori, Giovanni; Barjot, Catherine; Robinson, Ann S.; Robert W Crawford; Brooks, Susan V; Jeffrey S. Chamberlain

    2002-01-01

    Duchenne muscular dystrophy is a lethal X-linked recessive disorder caused by mutations in the dystrophin gene. Delivery of functionally effective levels of dystrophin to immunocompetent, adult mdx (dystrophin-deficient) mice has been challenging because of the size of the gene, immune responses against viral vectors, and inefficient infection of mature muscle. Here we show that high titer stocks of three different gutted adenoviral vectors carrying full-length, muscle-specific, dystrophin ex...

  3. Mitochondrial DNA deletion mutations in adult mouse cardiac side population cells

    Energy Technology Data Exchange (ETDEWEB)

    Lushaj, Entela B., E-mail: lushaj@surgery.wisc.edu [Division of Cardiothoracic Surgery, Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53792 (United States); Lozonschi, Lucian; Barnes, Maria; Anstadt, Emily; Kohmoto, Takushi [Division of Cardiothoracic Surgery, Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53792 (United States)

    2012-06-01

    We investigated the presence and potential role of mitochondrial DNA (mtDNA) deletion mutations in adult cardiac stem cells. Cardiac side population (SP) cells were isolated from 12-week-old mice. Standard polymerase chain reaction (PCR) was used to screen for the presence of mtDNA deletion mutations in (a) freshly isolated SP cells and (b) SP cells cultured to passage 10. When present, the abundance of mtDNA deletion mutation was analyzed in single cell colonies. The effect of different levels of deletion mutations on SP cell growth and differentiation was determined. MtDNA deletion mutations were found in both freshly isolated and cultured cells from 12-week-old mice. While there was no significant difference in the number of single cell colonies with mtDNA deletion mutations from any of the groups mentioned above, the abundance of mtDNA deletion mutations was significantly higher in the cultured cells, as determined by quantitative PCR. Within a single clonal cell population, the detectable mtDNA deletion mutations were the same in all cells and unique when compared to deletions of other colonies. We also found that cells harboring high levels of mtDNA deletion mutations (i.e. where deleted mtDNA comprised more than 60% of total mtDNA) had slower proliferation rates and decreased differentiation capacities. Screening cultured adult stem cells for mtDNA deletion mutations as a routine assessment will benefit the biomedical application of adult stem cells.

  4. Promotion of Cortical Neurogenesis from the Neural Stem Cells in the Adult Mouse Subcallosal Zone.

    Science.gov (United States)

    Kim, Joo Yeon; Choi, Kyuhyun; Shaker, Mohammed R; Lee, Ju-Hyun; Lee, Boram; Lee, Eunsoo; Park, Jae-Yong; Lim, Mi-Sun; Park, Chang-Hwan; Shin, Ki Soon; Kim, Hyun; Geum, Dongho; Sun, Woong

    2016-04-01

    Neurogenesis occurs spontaneously in the subventricular zone (SVZ) of the lateral ventricle in adult rodent brain, but it has long been debated whether there is sufficient adult neurogenesis in human SVZ. Subcallosal zone (SCZ), a posterior continuum of SVZ closely associated with posterior regions of cortical white matter, has also been reported to contain adult neural stem cells (aNSCs) in both rodents and humans. However, little is known whether SCZ-derived aNSC (SCZ-aNSCs) can produce cortical neurons following brain injury. We found that SCZ-aNSCs exhibited limited neuronal differentiation potential in culture and after transplantation in mice. Neuroblasts derived from SCZ initially migrated toward injured cortex regions following brain injury, but later exhibited apoptosis. Overexpression of anti-apoptotic bcl-xL in the SCZ by retroviral infection rescued neuroblasts from cell death in the injured cortex, but neuronal maturation was still limited, resulting in atrophy. In combination with Bcl-xL, infusion of brain-derived neurotropic factor rescued atrophy, and importantly, a subset of such SCZ-aNSCs differentiated and attained morphological and physiological characteristics of mature, excitatory neurons. These results suggest that the combination of anti-apoptotic and neurotrophic factors might enable the use of aNSCs derived from the SCZ in cortical neurogenesis for neural replacement therapy. Stem Cells 2016;34:888-901. PMID:26701067

  5. Adult neurogenesis and specific replacement of interneuron subtypes in the mouse main olfactory bulb

    Directory of Open Access Journals (Sweden)

    LaRocca Greg

    2007-11-01

    Full Text Available Abstract Background New neurons are generated in the adult brain from stem cells found in the subventricular zone (SVZ. These cells proliferate in the SVZ, generating neuroblasts which then migrate to the main olfactory bulb (MOB, ending their migration in the glomerular layer (GLL and the granule cell layer (GCL of the MOB. Neuronal populations in these layers undergo turnover throughout life, but whether all neuronal subtypes found in these areas are replaced and when neurons begin to express subtype-specific markers is not known. Results Here we use BrdU injections and immunohistochemistry against (calretinin, calbindin, N-copein, tyrosine hydroxylase and GABA and show that adult-generated neurons express markers of all major subtypes of neurons in the GLL and GCL. Moreover, the fractions of new neurons that express subtype-specific markers at 40 and 75 days post BrdU injection are very similar to the fractions of all neurons expressing these markers. We also show that many neurons in the glomerular layer do not express NeuN, but are readily and specifically labeled by the fluorescent nissl stain Neurotrace. Conclusion The expression of neuronal subtype-specific markers by new neurons in the GLL and GCL changes rapidly during the period from 14–40 days after BrdU injection before reaching adult levels. This period may represent a critical window for cell fate specification similar to that observed for neuronal survival.

  6. Curcumin Protects against UVB-Induced Skin Cancers in SKH-1 Hairless Mouse: Analysis of Early Molecular Markers in Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Kuen-Daw Tsai

    2012-01-01

    Full Text Available Curcumin (CUR has been shown to possess a preventive effect against various cancers and interfere with multiple-cell signaling pathways. We evaluated the protective effects of CUR in regression of UVB-induced skin tumor formation in SKH-1 hairless mice and its underlying early molecular biomarkers associated with carcinogenesis. Mice irradiated with UVB at 180 mJ/cm2 twice per week elicited 100% tumor incidence at 20 weeks. Topical application of CUR prior to UVB irradiation caused delay in tumor appearance, multiplicity, and size. Topical application of CUR prior to and immediately after a single UVB irradiation (180 mJ/cm2 resulted in a significant decrease in UVB-induced thymine dimer-positive cells, expression of proliferative cell nuclear antigen (PCNA, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and apoptotic sunburn cells together with an increase in p53 and p21/Cip1-positive cell population in epidermis. Simultaneously, CUR also significantly inhibited NF-κB, cyclooxygenase-2 (COX-2, prostaglandin E2 (PGE2, and nitric oxide (NO levels. The results suggest that the protective effect of CUR against photocarcinogenesis is accompanied by downregulation of cell proliferative controls, involving thymine dimer, PCNA, apoptosis, transcription factors NF-κB, and of inflammatory responses involving COX-2, PGE2, and NO, while upregulation of p53 and p21/Cip1 to prevent DNA damage and facilitate DNA repair.

  7. Reduced proliferation in the adult mouse subventricular zone increases survival of olfactory bulb interneurons.

    Directory of Open Access Journals (Sweden)

    Yi Sui

    Full Text Available Neurogenesis in the adult brain is largely restricted to the subependymal zone (SVZ of the lateral ventricle, olfactory bulb (OB and the dentate subgranular zone, and survival of adult-born cells in the OB is influenced by factors including sensory experience. We examined, in mice, whether survival of adult-born cells is also regulated by the rate of precursor proliferation in the SVZ. Precursor proliferation was decreased by depleting the SVZ of dopamine after lesioning dopamine neurons in the substantia nigra compacta with 6-hydroxydopamine. Subsequently, we examined the effect of reduced SVZ proliferation on the generation, migration and survival of neuroblasts and mature adult-born cells in the SVZ, rostral migratory stream (RMS and OB. Proliferating cells in the SVZ, measured by 5-bromo-2-deoxyuridine (BrdU injected 2 hours prior to death or by immunoreactivity against Ki67, were reduced by 47% or 36%, respectively, 7 days after dopamine depletion, and by 29% or 31% 42 days after dopamine depletion, compared to sham-treated animals. Neuroblast generation in the SVZ and their migration along the RMS were not affected, neither 7 nor 42 days after the 6-hydroxydopamine injection, since the number of doublecortin-immunoreactive neuroblasts in the SVZ and RMS, as well as the number of neuronal nuclei-immunoreactive cells in the OB, were stable compared to control. However, survival analysis 15 days after 6-hydroxydopamine and 6 days after BrdU injections showed that the number of BrdU+ cells in the SVZ was 70% higher. Also, 42 days after 6-hydroxydopamine and 30 days after BrdU injections, we found an 82% increase in co-labeled BrdU+/γ-aminobutyric acid-immunoreactive cell bodies in the granular cell layer, while double-labeled BrdU+/tyrosine hydroxylase-immunoreactive cell bodies in the glomerular layer increased by 148%. We conclude that the number of OB interneurons following reduced SVZ proliferation is maintained through an increased

  8. Radionecrosis skin model induced an athymic mouse nude (Nu/Nu) for development of dermal-epidermal human substitute based regenerative therapy

    International Nuclear Information System (INIS)

    The neoplasms incidence has increased significantly in recent years and continued population growth and aging will increase the statistics of this illness in the world's diseases. The cancer treatment usually consists in individual or combined use of chemotherapy, surgery and radiotherapy depending on the etiology of the tumor. In cases where radiotherapy is used in addition to the therapeutic effects of radiation, specific complications can occur, and in the skin, these complications can be present with a clinical expression ranging from erythema to radionecrosis, and this latter being the adverse effect with greater severity. The radionecrosis treatment consists in debridement necrotic areas and covering the surgical wounds. Autologous grafts are most commonly used for this covering, however when large areas are affected, allografts can be used for occlusive treatment and the keratinocytes and adipose derived stem cells (ADSC) addition becomes an alternative, due to the knowing for immunomodulatory and regenerative response. For that reason, aiming to simulate the radionecrosis adverse effects, an animal model of induced cutaneous radionecrosis was created, in athymic mouse Nude (Nu/Nu), for developing regenerative therapies based on human dermal-epidermal substitutes containing keratinocytes and ADSC, which proved occlusive as an efficient treatment, furthermore, having this radionecrosis animal model established, new possibilities for treatment of diseases involving dermal regeneration, can be tested. (author)

  9. Erucin Exerts Anti-Inflammatory Properties in Murine Macrophages and Mouse Skin: Possible Mediation through the Inhibition of NFκB Signaling

    Directory of Open Access Journals (Sweden)

    Ki Won Lee

    2013-10-01

    Full Text Available Erucin, an isothiocyanate, is a hydrolysis product of glucoerucin found in arugula and has recently been reported to have anti-cancer properties in various cancer cells. In this study, we assessed the anti-inflammatory effects of erucin and the underlying mechanisms, using lipopolysaccharide (LPS-stimulated RAW 264.7 murine macrophages and 12-O-tetradecanoylphorbol-13-acetate-treated mouse skin. In RAW 264.7 cells, erucin (2.5, 5 μmol/L inhibited LPS-induced production of nitric oxide and prostaglandin E2. Erucin inhibited LPS-induced degradation of the inhibitor of κBα and translocation of p65 to the nucleus and, subsequently, reduced LPS-induced nuclear factor κB (NFκB DNA binding activities, as well as the transcriptional activity of NFκB, leading to the decreased expression of NFκB-target genes, including tumor necrosis factor-α, interleukin (IL-6, IL-1β, inducible nitric oxide synthase (iNOS and cyclooxygenase (COX-2, as well as transcriptional activity of iNOS and COX-2. In mice, erucin (100, 300 nmoles treatment significantly inhibited phorbol ester-induced formation of ear edema and expression of iNOS and COX-2 proteins. These results indicate that erucin exerts a potent anti-inflammatory activity by inhibiting the pro-inflammatory enzymes and cytokines, which may be mediated, at least in part, via the inhibition of NFκB signaling.

  10. Erucin exerts anti-inflammatory properties in murine macrophages and mouse skin: possible mediation through the inhibition of NFκB signaling.

    Science.gov (United States)

    Cho, Han Jin; Lee, Ki Won; Park, Jung Han Yoon

    2013-10-15

    Erucin, an isothiocyanate, is a hydrolysis product of glucoerucin found in arugula and has recently been reported to have anti-cancer properties in various cancer cells. In this study, we assessed the anti-inflammatory effects of erucin and the underlying mechanisms, using lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages and 12-O-tetradecanoylphorbol-13-acetate-treated mouse skin. In RAW 264.7 cells, erucin (2.5, 5 μmol/L) inhibited LPS-induced production of nitric oxide and prostaglandin E2. Erucin inhibited LPS-induced degradation of the inhibitor of κBα and translocation of p65 to the nucleus and, subsequently, reduced LPS-induced nuclear factor κB (NFκB) DNA binding activities, as well as the transcriptional activity of NFκB, leading to the decreased expression of NFκB-target genes, including tumor necrosis factor-α, interleukin (IL)-6, IL-1β, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, as well as transcriptional activity of iNOS and COX-2. In mice, erucin (100, 300 nmoles) treatment significantly inhibited phorbol ester-induced formation of ear edema and expression of iNOS and COX-2 proteins. These results indicate that erucin exerts a potent anti-inflammatory activity by inhibiting the pro-inflammatory enzymes and cytokines, which may be mediated, at least in part, via the inhibition of NFκB signaling.

  11. Dietary lipid varying in corn and coconut oil influences protein kinase C in phorbol ester-treated mouse skin.

    Science.gov (United States)

    Mouat, M F; Locniskar, M F

    1998-01-01

    An earlier study indicated that increased levels of corn oil in the diet resulted in decreased tumor yield after promotion by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate in Sencar mouse epidermis (J Leyton, ML Lee, M Locniskar, MA Belury, TJ Slaga, et al. Cancer Res 51, 907-915, 1991). In the present study we investigated whether corn oil diets could alter the subcellular distribution and activity of protein kinase C (PKC), which is part of an important signaling pathway in carcinogenesis. We used three 15% (wt/wt) fat semipurified diets containing three ratios of corn oil to coconut oil: 1.0%:14.0% (Diet L), 7.9%:7.1% (Diet M), and 15.0%:0.0% (Diet H). The translocation to the membrane fraction of epidermal PKC by 12-O-tetradecanoylphorbol-13-acetate was decreased as the corn oil content of the diet was increased, and this correlates with the decrease in tumor yield. The translocation to the membrane fraction of specific isoforms of PKC was affected by increased dietary corn oil: the largest decreases were in cytosolic PKC-alpha and -beta, and the smallest change was in PKC-epsilon. The other isoforms, PKC-delta and -zeta, were unaffected. The major constituent of corn oil is linoleic acid, which did not affect the binding of phorbol ester to PKC, which suggests that inhibition of such binding was not responsible for the effects of increased dietary corn oil. Products of linoleic acid metabolism, i.e., arachidonic acid and 13-hydroxyoctadecadienoic acid, also did not affect the binding of phorbol ester to PKC. Thus the results of these studies suggest that the subcellular distributions of PKC and its isoforms can be modulated by dietary lipids.

  12. Olfactory discrimination training up-regulates and reorganizes expression of microRNAs in adult mouse hippocampus

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    Neil R Smalheiser

    2010-02-01

    Full Text Available Adult male mice (strain C57Bl/6J were trained to execute nose-poke responses for water reinforcement; then they were randomly assigned to either of two groups: olfactory discrimination training (exposed to two odours with reward contingent upon correctly responding to one odour or pseudo-training (exposed to two odours with reward not contingent upon response. These were run in yoked fashion and killed when the discrimination-trained mouse reached a learning criterion of 70% correct responses in 20 trials, occurring after three sessions (a total of ∼40 min of training. The hippocampus was dissected bilaterally from each mouse (N = 7 in each group and profiling of 585 miRNAs (microRNAs was carried out using multiplex RT–PCR (reverse transcription–PCR plates. A significant global up-regulation of miRNA expression was observed in the discrimination training versus pseudo-training comparison; when tested individually, 29 miRNAs achieved significance at P = 0.05. miR-10a showed a 2.7-fold increase with training, and is predicted to target several learning-related mRNAs including BDNF (brain-derived neurotrophic factor, CAMK2b (calcium/calmodulin-dependent protein kinase IIβ, CREB1 (cAMP-response-element-binding protein 1 and ELAVL2 [ELAV (embryonic lethal, abnormal vision, Drosophila-like; Hu B]. Analysis of miRNA pairwise correlations revealed the existence of several miRNA co-expression modules that were specific to the training group. These in vivo results indicate that significant, dynamic and co-ordinated changes in miRNA expression accompany early stages of learning.

  13. Bromelain nanoparticles protect against 7,12-dimethylbenz[a]anthracene induced skin carcinogenesis in mouse model.

    Science.gov (United States)

    Bhatnagar, Priyanka; Pant, Aditya B; Shukla, Yogeshwer; Chaudhari, Bhushan; Kumar, Pradeep; Gupta, Kailash C

    2015-04-01

    Conventional cancer chemotherapy leads to severe side effects, which limits its use. Nanoparticles (NPs) based delivery systems offer an effective alternative. Several evidences highlight the importance of Bromelain (BL), a proteolytic enzyme, as an anti-tumor agent which however has been limited due to the requirement of high doses at the tumor site. Therefore, we illustrate the development of BL loaded poly (lactic-co-glycolic acid) NPs that show enhanced anti-tumor effects compared to free BL. The formulated NPs with a mean particle size of 130.4 ± 8.81 nm exhibited sustained release of BL. Subsequent investigation revealed enhanced anti-tumor ability of NPs in 2-stage skin tumorigenesis mice model. Reduction in average number of tumors (∼ 2.3 folds), delay in tumorigenesis (∼ 2 weeks), percent tumorigenesis (∼ 4 folds), and percent mortality rate as well as a reduction in the average tumor volume (∼ 2.5 folds) in mice as compared to free BL were observed. The NPs were found to be superior in exerting chemopreventive effects over chemotherapeutic effects at 10 fold reduced dose than free BL, validated by the enhanced ability of NPs (∼ 1.8 folds) to protect the DNA from induced damage. The effects were also supported by histopathological evaluations. NPs were also capable of modulating the expression of pro-apoptotic (P53, Bax) and anti-apoptotic (Bcl2) proteins. Therefore, our findings demonstrate that developed NPs formulation could be used to improve the efficacy of chemotherapy by exerting chemo-preventive effects against induced carcinogenesis at lower dosages. PMID:25619920

  14. Characterizing newly repopulated microglia in the adult mouse: impacts on animal behavior, cell morphology, and neuroinflammation.

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    Monica R P Elmore

    Full Text Available Microglia are the primary immune cell in the brain and are postulated to play important roles outside of immunity. Administration of the dual colony-stimulating factor 1 receptor (CSF1R/c-Kit kinase inhibitor, PLX3397, to adult mice results in the elimination of ~99% of microglia, which remain eliminated for as long as treatment continues. Upon removal of the inhibitor, microglia rapidly repopulate the entire adult brain, stemming from a central nervous system (CNS resident progenitor cell. Using this method of microglial elimination and repopulation, the role of microglia in both healthy and diseased states can be explored. Here, we examine the responsiveness of newly repopulated microglia to an inflammatory stimulus, as well as determine the impact of these cells on behavior, cognition, and neuroinflammation. Two month-old wild-type mice were placed on either control or PLX3397 diet for 21 d to eliminate microglia. PLX3397 diet was then removed in a subset of animals to allow microglia to repopulate and behavioral testing conducted beginning at 14 d repopulation. Finally, inflammatory profiling of the microglia-repopulated brain in response to lipopolysaccharide (LPS; 0.25 mg/kg or phosphate buffered saline (PBS was determined 21 d after inhibitor removal using quantitative real time polymerase chain reaction (RT-PCR, as well as detailed analyses of microglial morphologies. We find mice with repopulated microglia to perform similarly to controls by measures of behavior, cognition, and motor function. Compared to control/resident microglia, repopulated microglia had larger cell bodies and less complex branching in their processes, which resolved over time after inhibitor removal. Inflammatory profiling revealed that the mRNA gene expression of repopulated microglia was similar to normal resident microglia and that these new cells appear functional and responsive to LPS. Overall, these data demonstrate that newly repopulated microglia function

  15. Characterizing newly repopulated microglia in the adult mouse: impacts on animal behavior, cell morphology, and neuroinflammation.

    Science.gov (United States)

    Elmore, Monica R P; Lee, Rafael J; West, Brian L; Green, Kim N

    2015-01-01

    Microglia are the primary immune cell in the brain and are postulated to play important roles outside of immunity. Administration of the dual colony-stimulating factor 1 receptor (CSF1R)/c-Kit kinase inhibitor, PLX3397, to adult mice results in the elimination of ~99% of microglia, which remain eliminated for as long as treatment continues. Upon removal of the inhibitor, microglia rapidly repopulate the entire adult brain, stemming from a central nervous system (CNS) resident progenitor cell. Using this method of microglial elimination and repopulation, the role of microglia in both healthy and diseased states can be explored. Here, we examine the responsiveness of newly repopulated microglia to an inflammatory stimulus, as well as determine the impact of these cells on behavior, cognition, and neuroinflammation. Two month-old wild-type mice were placed on either control or PLX3397 diet for 21 d to eliminate microglia. PLX3397 diet was then removed in a subset of animals to allow microglia to repopulate and behavioral testing conducted beginning at 14 d repopulation. Finally, inflammatory profiling of the microglia-repopulated brain in response to lipopolysaccharide (LPS; 0.25 mg/kg) or phosphate buffered saline (PBS) was determined 21 d after inhibitor removal using quantitative real time polymerase chain reaction (RT-PCR), as well as detailed analyses of microglial morphologies. We find mice with repopulated microglia to perform similarly to controls by measures of behavior, cognition, and motor function. Compared to control/resident microglia, repopulated microglia had larger cell bodies and less complex branching in their processes, which resolved over time after inhibitor removal. Inflammatory profiling revealed that the mRNA gene expression of repopulated microglia was similar to normal resident microglia and that these new cells appear functional and responsive to LPS. Overall, these data demonstrate that newly repopulated microglia function similarly to the

  16. Treatment of green tea polyphenols in hydrophilic cream prevents UVB-induced oxidation of lipids and proteins, depletion of antioxidant enzymes and phosphorylation of MAPK proteins in SKH-1 hairless mouse skin.

    Science.gov (United States)

    Vayalil, Praveen K; Elmets, Craig A; Katiyar, Santosh K

    2003-05-01

    The use of botanical supplements has received immense interest in recent years to protect human skin from adverse biological effects of solar ultraviolet (UV) radiation. The polyphenols from green tea are one of them and have been shown to prevent photocarcinogenesis in animal models but their mechanism of photoprotection is not well understood. To determine the mechanism of photoprotection in in vivo mouse model, topical treatment of polyphenols from green tea (GTP) or its most chemopreventive constituent (-)-epigallocatechin-3-gallate (EGCG) (1 mg/cm(2) skin area) in hydrophilic ointment USP before single (180 mJ/cm(2)) or multiple UVB exposures (180 mJ/cm(2), daily for 10 days) resulted in significant prevention of UVB-induced depletion of antioxidant enzymes such as glutathione peroxidase (78-100%, P 0.001). Further, to delineate the inhibition of UVB-induced oxidative stress with cell signaling pathways, treatment of EGCG to mouse skin resulted in marked inhibition of a single UVB irradiation-induced phosphorylation of ERK1/2 (16-95%), JNK (46-100%) and p38 (100%) proteins of MAPK family in a time-dependent manner. Identical photoprotective effects of EGCG or GTP were also observed against multiple UVB irradiation-induced phosphorylation of the proteins of MAPK family in vivo mouse skin. Photoprotective efficacy of GTP given in drinking water (d.w.) (0.2%, w/v) was also determined and compared with that of topical treatment of EGCG and GTP. Treatment of GTP in d.w. also significantly prevented single or multiple UVB irradiation-induced depletion of antioxidant enzymes (44-61%, P the possibility of its use for the humans, and the data obtained from this in vivo study further suggest that GTP could be useful in attenuation of solar UVB light-induced oxidative stress-mediated and MAPK-caused skin disorders in humans. PMID:12771038

  17. Morphological analysis of activity-reduced adult-born neurons in the mouse olfactory bulb

    Directory of Open Access Journals (Sweden)

    Jeffrey E Dahlen

    2011-05-01

    Full Text Available Adult born neurons are added to the olfactory bulb (OB throughout life in rodents. While many factors have been identified as regulating the survival and integration of adult-born neurons (ABNs into existing circuitry, the understanding of how these factors affect ABN morphology and connectivity is limited. Here we compare how cell intrinsic (siRNA knock down of voltage gated sodium channels NaV1.1-1.3 and circuit level (naris occlusion reductions in activity affect ABN morphology during integration into the OB. We found that both manipulations reduce the number of dendritic spines (and thus likely the number of reciprocal synaptic connections formed with the surrounding circuitry and inhibited dendritic ramification of ABNs. Further, we identified regions of ABN apical dendrites where the largest and most significant decreases occur following siRNA knock down or naris occlusion. In siRNA knock down cells, reduction of spines is observed in proximal regions of the apical dendrite. This suggests that distal regions of the dendrite may remain active independent of NaV1.1-1.3 channel expression, perhaps facilitated by activation of T-type calcium channels and NMDA receptors. By contrast, circuit level reduction of activity by naris occlusion resulted in a global depression of spine number. Together, these results indicate that ABNs retain the ability to develop their typical overall morphological features regardless of experienced activity, and activity modulates the number and location of formed connections.

  18. CD133 does not enrich for the stem cell activity in vivo in adult mouse prostates

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    Xing Wei

    2016-05-01

    Full Text Available CD133 is widely used as a marker for stem/progenitor cells in many organ systems. Previous studies using in vitro stem cell assays have suggested that the CD133-expressing prostate basal cells may serve as the putative prostate stem cells. However, the precise localization of the CD133-expressing cells and their contributions to adult murine prostate homeostasis in vivo remain undetermined. We show that loss of function of CD133 does not impair murine prostate morphogenesis, homeostasis and regeneration, implying a dispensable role for CD133 in prostate stem cell function. Using a CD133-CreERT2 model in conjunction with a fluorescent report line, we show that CD133 is not only expressed in a fraction of prostate basal cells, but also in some luminal cells and stromal cells. CD133+ basal cells possess higher in vitro sphere-forming activities than CD133− basal cells. However, the in vivo lineage tracing study reveals that the two cell populations possess the same regenerative capacity and contribute equally to the maintenance of the basal cell lineage. Similarly, CD133+ and CD133− luminal cells are functionally equivalent in maintaining the luminal cell lineage. Collectively, our study demonstrates that CD133 does not enrich for the stem cell activity in vivo in adult murine prostate. This study does not contradict previous reports showing CD133+ cells as prostate stem cells in vitro. Instead, it highlights a substantial impact of biological contexts on cellular behaviors.

  19. Differential genomic imprinting regulates paracrine and autocrine roles of IGF2 in mouse adult neurogenesis.

    Science.gov (United States)

    Ferrón, S R; Radford, E J; Domingo-Muelas, A; Kleine, I; Ramme, A; Gray, D; Sandovici, I; Constancia, M; Ward, A; Menheniott, T R; Ferguson-Smith, A C

    2015-01-01

    Genomic imprinting is implicated in the control of gene dosage in neurogenic niches. Here we address the importance of Igf2 imprinting for murine adult neurogenesis in the subventricular zone (SVZ) and in the subgranular zone (SGZ) of the hippocampus in vivo. In the SVZ, paracrine IGF2 is a cerebrospinal fluid and endothelial-derived neurogenic factor requiring biallelic expression, with mutants having reduced activation of the stem cell pool and impaired olfactory bulb neurogenesis. In contrast, Igf2 is imprinted in the hippocampus acting as an autocrine factor expressed in neural stem cells (NSCs) solely from the paternal allele. Conditional mutagenesis of Igf2 in blood vessels confirms that endothelial-derived IGF2 contributes to NSC maintenance in SVZ but not in the SGZ, and that this is regulated by the biallelic expression of IGF2 in the vascular compartment. Our findings indicate that a regulatory decision to imprint or not is a functionally important mechanism of transcriptional dosage control in adult neurogenesis. PMID:26369386

  20. Carcinogenicity of the environmental pollutants cyclopenteno-(cd)pyrene and cyclopentano(cd)pyrene in mouse skin

    Energy Technology Data Exchange (ETDEWEB)

    Cavalieri, E.; Rogan, E.; Toth, B.; Munhall, A.

    1981-01-01

    Cyclopenteno(cd)pyrene (CPEP) is a widespread environmental pollutant. This hydrocarbon and its 3,4-dihydro derivative, cyclopentano(cd)pyrene (CPAP), were tested on skin in a two-stage initiation-promotion experiment in CD-1 mice and by repeated application in Swiss mice. The biological effect of CPEP and CPAP was compared to that of benzo(a)-pyrene (BP). Nine-week-old female CD-1 mice in groups of 30 were treated every other day over a 20-day period at mini-dose levels of 0.18, 0.06 and 0.02 mumol of CPEP or CPAP in acetone. One group was treated with BP at the low mini-dose level. Initiation was followed by twice weekly application of tetradecanoyl phorbol acetate for 40 weeks. In the second experiments, nine-week-old female Swiss mice in groups of 30 were treated at dose levels of 1.8, 0.6 and 0.2 mumol CPEP or CPAP in acetone twice weekly for 30 weeks. One group was treated with BP at the low dose. CPAP was virtually inactive in both studies. In the initiation-promotion experiment CPEP was inactive at the low dose level, whereas BP exhibited significant tumorigenicity. At the medium and high doses CPEP showed weak, but statistically insignificant, tumorigenic activity. Repeated application of CPEP at the high, medium and low doses resulted in tumor incidences of 23, 37 and 57%, respectively. This reverse dose-response may be due to the relatively high cytotoxicity of CPEP, BP, which was compared to CPEP at the low dose, elicited tumors in 100% of the mice. Most of the CPEP-induced neoplasms were malignant and some metastasized to lungs and lymph nodes. The inactivity of CPAP suggests the carcinogenicity of CPEP is probably due to formation of the ultimate metabolite CPEP 3,4-oxide. In view of the abundance of CPEP in environmental and occupational pollutants, its moderately potent carcinogenicity may represent a potential health hazard.

  1. Changes in the distribution pattern of Claudin tight junction proteins during the progression of mouse skin tumorigenesis

    International Nuclear Information System (INIS)

    epidermis) remained restricted to the cell membrane throughout the tumorigenesis protocol. However commencing 2 weeks after treatment there was a marked decrease in the number of Cldn1-positive basal cells, and the zone of Cldn1-null epidermal cells was expanded up into the lower stratified epidermis throughout the progression of DMBA/TPA treatment. In addition, there was no Cldn1 localization in the infiltrating epidermal structures of the tumorigenic epidermis. This is the first demonstration of the changes in Cldn expression in the progression of DMBA/TPA-induced skin tumors; however further investigation into the molecular mechanisms regulating the observed changes in barrier selectivity during tumorigenesis is required

  2. A fluid secretion pathway unmasked by acinar-specific Tmem16A gene ablation in the adult mouse salivary gland.

    Science.gov (United States)

    Catalán, Marcelo A; Kondo, Yusuke; Peña-Munzenmayer, Gaspar; Jaramillo, Yasna; Liu, Frances; Choi, Sooji; Crandall, Edward; Borok, Zea; Flodby, Per; Shull, Gary E; Melvin, James E

    2015-02-17

    Activation of an apical Ca(2+)-activated Cl(-) channel (CaCC) triggers the secretion of saliva. It was previously demonstrated that CaCC-mediated Cl(-) current and Cl(-) efflux are absent in the acinar cells of systemic Tmem16A (Tmem16A Cl(-) channel) null mice, but salivation was not assessed in fully developed glands because Tmem16A null mice die within a few days after birth. To test the role of Tmem16A in adult salivary glands, we generated conditional knockout mice lacking Tmem16A in acinar cells (Tmem16A(-/-)). Ca(2+)-dependent salivation was abolished in Tmem16A(-/-) mice, demonstrating that Tmem16A is obligatory for Ca(2+)-mediated fluid secretion. However, the amount of saliva secreted by Tmem16A(-/-) mice in response to the β-adrenergic receptor agonist isoproterenol (IPR) was comparable to that seen in controls, indicating that Tmem16A does not significantly contribute to cAMP-induced secretion. Furthermore, IPR-stimulated secretion was unaffected in mice lacking Cftr (Cftr(∆F508/∆F508)) or ClC-2 (Clcn2(-/-)) Cl(-) channels. The time course for activation of IPR-stimulated fluid secretion closely correlated with that of the IPR-induced cell volume increase, suggesting that acinar swelling may activate a volume-sensitive Cl(-) channel. Indeed, Cl(-) channel blockers abolished fluid secretion, indicating that Cl(-) channel activity is critical for IPR-stimulated secretion. These data suggest that β-adrenergic-induced, cAMP-dependent fluid secretion involves a volume-regulated anion channel. In summary, our results using acinar-specific Tmem16A(-/-) mice identify Tmem16A as the Cl(-) channel essential for muscarinic, Ca(2+)-dependent fluid secretion in adult mouse salivary glands.

  3. Build a better mouse: directly-observed issues in computer use for adults with SMI.

    Science.gov (United States)

    Black, Anne C; Serowik, Kristin L; Schensul, Jean J; Bowen, Anne M; Rosen, Marc I

    2013-03-01

    Integrating information technology into healthcare has the potential to bring treatment to hard-to-reach people. Individuals with serious mental illness (SMI), however, may derive limited benefit from these advances in care because of lack of computer ownership and experience. To date, conclusions about the computer skills and attitudes of adults with SMI have been based primarily on self-report. In the current study, 28 psychiatric outpatients with co-occurring cocaine use were interviewed about their computer use and opinions, and 25 were then directly observed using task analysis and think aloud methods as they navigated a multi-component health informational website. Participants reported low rates of computer ownership and use, and negative attitudes towards computers. Self-reported computer skills were higher than demonstrated in the task analysis. However, some participants spontaneously expressed more positive attitudes and greater computer self-efficacy after navigating the website. Implications for increasing access to computer-based health information are discussed.

  4. Synaptic pathology and therapeutic repair in adult retinoschisis mouse by AAV-RS1 transfer.

    Science.gov (United States)

    Ou, Jingxing; Vijayasarathy, Camasamudram; Ziccardi, Lucia; Chen, Shan; Zeng, Yong; Marangoni, Dario; Pope, Jodie G; Bush, Ronald A; Wu, Zhijian; Li, Wei; Sieving, Paul A

    2015-07-01

    Strategies aimed at invoking synaptic plasticity have therapeutic potential for several neurological conditions. The human retinal synaptic disease X-linked retinoschisis (XLRS) is characterized by impaired visual signal transmission through the retina and progressive visual acuity loss, and mice lacking retinoschisin (RS1) recapitulate human disease. Here, we demonstrate that restoration of RS1 via retina-specific delivery of adeno-associated virus type 8-RS1 (AAV8-RS1) vector rescues molecular pathology at the photoreceptor-depolarizing bipolar cell (photoreceptor-DBC) synapse and restores function in adult Rs1-KO animals. Initial development of the photoreceptor-DBC synapse was normal in the Rs1-KO retina; however, the metabotropic glutamate receptor 6/transient receptor potential melastatin subfamily M member 1-signaling (mGluR6/TRPM1-signaling) cascade was not properly maintained. Specifically, the TRPM1 channel and G proteins Gαo, Gβ5, and RGS11 were progressively lost from postsynaptic DBC dendritic tips, whereas the mGluR6 receptor and RGS7 maintained proper synaptic position. This postsynaptic disruption differed from other murine night-blindness models with an electronegative electroretinogram response, which is also characteristic of murine and human XLRS disease. Upon AAV8-RS1 gene transfer to the retina of adult XLRS mice, TRPM1 and the signaling molecules returned to their proper dendritic tip location, and the DBC resting membrane potential was restored. These findings provide insight into the molecular plasticity of a critical synapse in the visual system and demonstrate potential therapeutic avenues for some diseases involving synaptic pathology. PMID:26098217

  5. 3D culture of adult mouse neural stem cells within functionalized self-assembling peptide scaffolds

    Directory of Open Access Journals (Sweden)

    Cunha C

    2011-05-01

    Full Text Available Carla Cunha1,2, Silvia Panseri3,4, Omar Villa1,2, Diego Silva1,2, Fabrizio Gelain1,21Department of Biotechnology and Biosciences, University of Milano-Bicocca; 2Center for Nanomedicine and Tissue Engineering, CNTE – A.O. Ospedale Niguarda Ca' Granda, Milan; 3Laboratory of Biomechanics and Technology Innovation, Rizzoli Orthopaedic Institute, Bologna; 4Laboratory of Nano-Biomagnetism, Institute of Science and Technology for Ceramics, National Research Council, Faenza, ItalyAbstract: Three-dimensional (3D in vitro models of cell culture aim to fill the gap between the standard two-dimensional cell studies and the in vivo environment. Especially for neural tissue regeneration approaches where there is little regenerative capacity, these models are important for mimicking the extracellular matrix in providing support, allowing the natural flow of oxygen, nutrients, and growth factors, and possibly favoring neural cell regrowth. We have previously demonstrated that a new self-assembling nanostructured biomaterial, based on matrigel, was able to support adult neural stem cell (NSC culture. In this study, we developed a new 3D cell culture system that takes advantage of the nano- and microfiber assembling process, under physiologic conditions, of these biomaterials. The assembled scaffold forms an intricate and biologically active matrix that displays specifically designed functional motifs: RGD (Arg-Gly-Asp, BMHP1 (bone marrow homing peptide 1, and BMHP2, for the culture of adult NSCs. These scaffolds were prepared at different concentrations, and microscopic examination of the cell-embedded scaffolds showed that NSCs are viable and they proliferate and differentiate within the nanostructured environment of the scaffold. Such a model has the potential to be tailored to develop ad hoc designed peptides for specific cell lines.Keywords: biomaterials, tissue engineering, 3D in vitro model

  6. The transformation of synaptic to system plasticity in motor output from the sacral cord of the adult mouse.

    Science.gov (United States)

    Jiang, Mingchen C; Elbasiouny, Sherif M; Collins, William F; Heckman, C J

    2015-09-01

    Synaptic plasticity is fundamental in shaping the output of neural networks. The transformation of synaptic plasticity at the cellular level into plasticity at the system level involves multiple factors, including behavior of local networks of interneurons. Here we investigate the synaptic to system transformation for plasticity in motor output in an in vitro preparation of the adult mouse spinal cord. System plasticity was assessed from compound action potentials (APs) in spinal ventral roots, which were generated simultaneously by the axons of many motoneurons (MNs). Synaptic plasticity was assessed from intracellular recordings of MNs. A computer model of the MN pool was used to identify the middle steps in the transformation from synaptic to system behavior. Two input systems that converge on the same MN pool were studied: one sensory and one descending. The two synaptic input systems generated very different motor outputs, with sensory stimulation consistently evoking short-term depression (STD) whereas descending stimulation had bimodal plasticity: STD at low frequencies but short-term facilitation (STF) at high frequencies. Intracellular and pharmacological studies revealed contributions from monosynaptic excitation and stimulus time-locked inhibition but also considerable asynchronous excitation sustained from local network activity. The computer simulations showed that STD in the monosynaptic excitatory input was the primary driver of the system STD in the sensory input whereas network excitation underlies the bimodal plasticity in the descending system. These results provide insight on the roles of plasticity in the monosynaptic and polysynaptic inputs converging on the same MN pool to overall motor plasticity.

  7. Induced neural stem cells achieve long-term survival and functional integration in the adult mouse brain.

    Science.gov (United States)

    Hemmer, Kathrin; Zhang, Mingyue; van Wüllen, Thea; Sakalem, Marna; Tapia, Natalia; Baumuratov, Aidos; Kaltschmidt, Christian; Kaltschmidt, Barbara; Schöler, Hans R; Zhang, Weiqi; Schwamborn, Jens C

    2014-09-01

    Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]). iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC) technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications. PMID:25241741

  8. Induced Neural Stem Cells Achieve Long-Term Survival and Functional Integration in the Adult Mouse Brain

    Directory of Open Access Journals (Sweden)

    Kathrin Hemmer

    2014-09-01

    Full Text Available Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]. iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications.

  9. Astrocytic adaptation during cerebral angiogenesis follows the new vessel formation induced through chronic hypoxia in adult mouse cortex

    Science.gov (United States)

    Masamoto, Kazuto; Kanno, Iwao

    2014-03-01

    We examined longitudinal changes of the neuro-glia-vascular unit during cerebral angiogenesis induced through chronic hypoxia in the adult mouse cortex. Tie2-GFP mice in which the vascular endothelial cells expressed green fluorescent proteins (GFP) were exposed to chronic hypoxia, while the spatiotemporal developments of the cortical capillary sprouts and the neighboring astrocytic remodeling were characterized with repeated two-photon microscopy. The capillary sprouts appeared at early phases of the hypoxia adaptation (1-2 weeks), while the morphological changes of the astrocytic soma and processes were not detected in this phase. In the later phases of the hypoxia adaptation (> 2 weeks), the capillary sprouts created a new connection with existing capillaries, and its neighboring astrocytes extended their processes to the newly-formed vessels. The findings show that morphological adaptation of the astrocytes follow the capillary development during the hypoxia adaptation, which indicate that the newly-formed vessels provoke cellular interactions with the neighboring astrocytes to strengthen the functional blood-brain barrier.

  10. Polycyclic aromatic hydrocarbons as skin carcinogens: Comparison of benzo[a]pyrene, dibenzo[def,p]chrysene and three environmental mixtures in the FVB/N mouse

    Energy Technology Data Exchange (ETDEWEB)

    Siddens, Lisbeth K.; Larkin, Andrew [Department of Environmental and Molecular Toxicology, Oregon State University (United States); Superfund Research Center, Oregon State University (United States); Krueger, Sharon K. [Superfund Research Center, Oregon State University (United States); The Linus Pauling Institute, Oregon State University (United States); Bradfield, Christopher A. [McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI 53706 (United States); Waters, Katrina M.; Tilton, Susan C. [Superfund Research Center, Oregon State University (United States); Computational Biology and Bioinformatics Group, Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Pereira, Cliff B. [Superfund Research Center, Oregon State University (United States); Deptartment of Statistics, Oregon State University, Corvallis, OR 97331 (United States); Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); Löhr, Christiane V. [Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331 (United States); Arlt, Volker M.; Phillips, David H. [Analytical and Environmental Sciences Division, MRC-HPA Centre for Environment and Health, King' s College London, London SE1 9NH (United Kingdom); Williams, David E., E-mail: david.williams@oregonstate.edu [Department of Environmental and Molecular Toxicology, Oregon State University (United States); Superfund Research Center, Oregon State University (United States); The Linus Pauling Institute, Oregon State University (United States); Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); and others

    2012-11-01

    The polycyclic aromatic hydrocarbon (PAH), benzo[a]pyrene (BaP), was compared to dibenzo[def,p]chrysene (DBC) and combinations of three environmental PAH mixtures (coal tar, diesel particulate and cigarette smoke condensate) using a two stage, FVB/N mouse skin tumor model. DBC (4 nmol) was most potent, reaching 100% tumor incidence with a shorter latency to tumor formation, less than 20 weeks of 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion compared to all other treatments. Multiplicity was 4 times greater than BaP (400 nmol). Both PAHs produced primarily papillomas followed by squamous cell carcinoma and carcinoma in situ. Diesel particulate extract (1 mg SRM 1650b; mix 1) did not differ from toluene controls and failed to elicit a carcinogenic response. Addition of coal tar extract (1 mg SRM 1597a; mix 2) produced a response similar to BaP. Further addition of 2 mg of cigarette smoke condensate (mix 3) did not alter the response with mix 2. PAH-DNA adducts measured in epidermis 12 h post initiation and analyzed by {sup 32}P post‐labeling, did not correlate with tumor incidence. PAH‐dependent alteration in transcriptome of skin 12 h post initiation was assessed by microarray. Principal component analysis (sum of all treatments) of the 922 significantly altered genes (p < 0.05), showed DBC and BaP to cluster distinct from PAH mixtures and each other. BaP and mixtures up-regulated phase 1 and phase 2 metabolizing enzymes while DBC did not. The carcinogenicity with DBC and two of the mixtures was much greater than would be predicted based on published Relative Potency Factors (RPFs). -- Highlights: ► Dibenzo[def,p]chrysene (DBC), 3 PAH mixtures, benzo[a]pyrene (BaP) were compared. ► DBC and 2 PAH mixtures were more potent than Relative Potency Factor estimates. ► Transcriptome profiles 12 hours post initiation were analyzed by microarray. ► Principle components analysis of alterations revealed treatment-based clustering. ► DBC gave a unique

  11. Daily rhythms of core temperature and locomotor activity indicate different adaptive strategies to cold exposure in adult and aged mouse lemurs acclimated to a summer-like photoperiod.

    OpenAIRE

    Terrien, Jeremy; Zizzari, Philippe; Epelbaum, Jacques; Perret, Martine; Aujard, Fabienne

    2009-01-01

    Daily variations in core temperature (Tc) within the normothermic range imply thermoregulatory processes that are essential for optimal function and survival. Higher susceptibility towards cold exposure in older animals suggests that these processes are disturbed with age. In the mouse lemur, a long-day breeder, we tested whether aging affected circadian rhythmicity of Tc, locomotor activity (LA), and energy balance under long-day conditions when exposed to cold. Adult (N = 7) and aged (N = 5...

  12. Characterization of Aromatase Expression in the Adult Male and Female Mouse Brain. I. Coexistence with Oestrogen Receptors α and β, and Androgen Receptors

    OpenAIRE

    Davor Stanić; Sydney Dubois; Hui Kheng Chua; Bruce Tonge; Nicole Rinehart; Malcolm K Horne; Wah Chin Boon

    2014-01-01

    Aromatase catalyses the last step of oestrogen synthesis. There is growing evidence that local oestrogens influence many brain regions to modulate brain development and behaviour. We examined, by immunohistochemistry, the expression of aromatase in the adult male and female mouse brain, using mice in which enhanced green fluorescent protein (EGFP) is transcribed following the physiological activation of the Cyp19A1 gene. EGFP-immunoreactive processes were distributed in many brain regions, in...

  13. Cytochrome P450 1b1 in polycyclic aromatic hydrocarbon (PAH)-induced skin carcinogenesis: Tumorigenicity of individual PAHs and coal-tar extract, DNA adduction and expression of select genes in the Cyp1b1 knockout mouse

    Energy Technology Data Exchange (ETDEWEB)

    Siddens, Lisbeth K. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331 (United States); Superfund Research Center, Oregon State University, Corvallis, OR 97331 (United States); Bunde, Kristi L. [College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331 (United States); Harper, Tod A. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331 (United States); Linus Pauling Institute, Oregon State University, Corvallis, OR 97331 (United States); Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); McQuistan, Tammie J. [Superfund Research Center, Oregon State University, Corvallis, OR 97331 (United States); Linus Pauling Institute, Oregon State University, Corvallis, OR 97331 (United States); Löhr, Christiane V. [Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331 (United States); Bramer, Lisa M. [Applied Statistics and Computational Modeling, Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Waters, Katrina M. [Superfund Research Center, Oregon State University, Corvallis, OR 97331 (United States); Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Tilton, Susan C. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331 (United States); Superfund Research Center, Oregon State University, Corvallis, OR 97331 (United States); Krueger, Sharon K. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331 (United States); Superfund Research Center, Oregon State University, Corvallis, OR 97331 (United States); Linus Pauling Institute, Oregon State University, Corvallis, OR 97331 (United States); and others

    2015-09-01

    FVB/N mice wild-type, heterozygous or null for Cyp 1b1 were used in a two-stage skin tumor study comparing PAH, benzo[a]pyrene (BaP), dibenzo[def,p]chrysene (DBC), and coal tar extract (CTE, SRM 1597a). Following 20 weeks of promotion with TPA the Cyp 1b1 null mice, initiated with DBC, exhibited reductions in incidence, multiplicity, and progression. None of these effects were observed with BaP or CTE. The mechanism of Cyp 1b1-dependent alteration of DBC skin carcinogenesis was further investigated by determining expression of select genes in skin from DBC-treated mice 2, 4 and 8 h post-initiation. A significant reduction in levels of Cyp 1a1, Nqo1 at 8 h and Akr 1c14 mRNA was observed in Cyp 1b1 null (but not wt or het) mice, whereas no impact was observed in Gst a1, Nqo 1 at 2 and 4 h or Akr 1c19 at any time point. Cyp 1b1 mRNA was not elevated by DBC. The major covalent DNA adducts, dibenzo[def,p]chrysene-(±)-11,12-dihydrodiol-cis and trans-13,14-epoxide-deoxyadenosine (DBCDE-dA) were quantified by UHPLC-MS/MS 8 h post-initiation. Loss of Cyp1 b1 expression reduced DBCDE-dA adducts in the skin but not to a statistically significant degree. The ratio of cis- to trans-DBCDE-dA adducts was higher in the skin than other target tissues such as the spleen, lung and liver (oral dosing). These results document that Cyp 1b1 plays a significant role in bioactivation and carcinogenesis of DBC in a two-stage mouse skin tumor model and that loss of Cyp 1b1 has little impact on tumor response with BaP or CTE as initiators. - Highlights: • Cyp1b1 null mice exhibit lower skin cancer sensitivity to DBC but not BaP or CTE. • Cyp1b1 expression impacts expression of other PAH metabolizing enzymes. • cis/trans-DBCDE-dA ratio significantly higher in the skin than the spleen, lung or liver • Potency of DBC and CTE in mouse skin is higher than predicted by RPFs.

  14. Expression and regulation of the Fkbp5 gene in the adult mouse brain.

    Directory of Open Access Journals (Sweden)

    Sebastian H Scharf

    Full Text Available BACKGROUND: Chronic stress has been found to be a major risk factor for various human pathologies. Stress activates the hypothalamic-pituitary-adrenal (HPA axis, which is tightly regulated via, among others, the glucocorticoid receptor (GR. The activity of the GR is modulated by a variety of proteins, including the co-chaperone FK506 binding protein 51 (FKBP5. Although FKBP5 has been associated with risk for affective disorders and has been implicated in GR sensitivity, previous studies focused mainly on peripheral blood, while information about basal distribution and induction in the central nervous system are sparse. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we describe the basal expression pattern of Fkbp5 mRNA in the brain of adult male mice and show the induction of Fkbp5 mRNA via dexamethasone treatment or different stress paradigms. We could show that Fkbp5 is often, but not exclusively, expressed in regions also known for GR expression, for example the hippocampus. Furthermore, we were able to induce Fkbp5 expression via dexamethasone in the CA1 and DG subregions of the hippocampus, the paraventricular nucleus (PVN and the central amygdala (CeA. Increase of Fkbp5 mRNA was also found after restrained stress and 24 hours of food deprivation in the PVN and the CeA, while in the hippocampus only food deprivation caused an increase in Fkbp5 mRNA. CONCLUSIONS/SIGNIFICANCE: Interestingly, regions with a low basal expression showed higher increase in Fkbp5 mRNA following induction than regions with high basal expression, supporting the hypothesis that GR sensitivity is, at least partly, mediated via Fkbp5. In addition, this also supports the use of Fkbp5 gene expression as a marker for GR sensitivity. In summary, we were able to give an overview of the basal expression of fkbp5 mRNA as well as to extend the findings of induction of Fkbp5 and its regulatory influence on GR sensitivity from peripheral blood to the brain.

  15. Common burden of chronic skin diseases? Contributors to psychological distress in adults with psoriasis and atopic dermatitis.

    NARCIS (Netherlands)

    Evers, A.W.M.; Lu, Y.; Duller, P.; Valk, P.G.M. van der; Kraaimaat, F.W.; Kerkhof, P.C.M. van de

    2005-01-01

    BACKGROUND: Chronic skin diseases, such as atopic dermatitis and psoriasis, are known to affect quality of life by heightening psychological distress. Knowledge about factors contributing to psychological distress is essential for supporting physicians in diagnostic and multidisciplinary treatment o

  16. Skin conductance biofeedback training in adults with drug-resistant temporal lobe epilepsy and stress-triggered seizures: a proof-of-concept study.

    Science.gov (United States)

    Micoulaud-Franchi, Jean-Arthur; Kotwas, Iliana; Lanteaume, Laura; Berthet, Christelle; Bastien, Mireille; Vion-Dury, Jean; McGonigal, Aileen; Bartolomei, Fabrice

    2014-12-01

    The present proof-of-concept study investigated the feasibility of skin conductance biofeedback training in reducing seizures in adults with drug-resistant temporal lobe epilepsy (TLE), whose seizures are triggered by stress. Skin conductance biofeedback aims to increase levels of peripheral sympathetic arousal in order to reduce cortical excitability. This might seem somewhat counterintuitive, since such autonomic arousal may also be associated with increased stress and anxiety. Thus, this sought to verify that patients with TLE and stress-triggered seizures are not worsened in terms of stress, anxiety, and negative emotional response to this nonpharmacological treatment. Eleven patients with drug-resistant TLE with seizures triggered by stress were treated with 12 sessions of biofeedback. Patients did not worsen on cognitive evaluation of attentional biases towards negative emotional stimuli (P>.05) or on psychometric evaluation with state anxiety inventory (P = .059); in addition, a significant improvement was found in the Negative Affect Schedule (P = .014) and in the Beck Depression Inventory (P = .009). Biofeedback training significantly reduced seizure frequency with a mean reduction of -48.61% (SD = 27.79) (P = .005). There was a correlation between the mean change in skin conductance activity over the biofeedback treatment and the reduction of seizure frequency (r(11) = .62, P = .042). Thus, the skin conductance biofeedback used in the present study, which teaches patients to achieve an increased level of peripheral sympathetic arousal, was a well-tolerated nonpharmacological treatment. Further, well-controlled studies are needed to confirm the therapeutic value of this nonpharmacological treatment in reducing seizures in adults with drug-resistant TLE with seizures triggered by stress. PMID:25461224

  17. About Skin-to-Skin Care (Kangaroo Care)

    Science.gov (United States)

    ... Prenatal Baby Bathing & Skin Care Breastfeeding Crying & Colic Diapers & Clothing Feeding & Nutrition Preemie Sleep Teething & Tooth Care Toddler Preschool Gradeschool Teen Young Adult Healthy Children > Ages & Stages > Baby > Preemie > About Skin- ...

  18. Evaluation of educational videos to increase skin cancer risk awareness and sun-safe behaviors among adult Hispanics.

    Science.gov (United States)

    Hernandez, Claudia; Wang, Stephanie; Abraham, Ivy; Angulo, Maria Isabel; Kim, Hajwa; Meza, Joyce R; Munoz, Anastasia; Rodriguez, Lizbeth; Uddin, Sabrina

    2014-09-01

    Although skin cancer is less common in Hispanics, they are at higher risk for presenting with more advanced stage skin cancer. We performed semi-structured interviews with Hispanic women that found high concern for photoaging from sun exposure. Based on these results, we developed two short Spanish-language films. The first emphasized photoaging benefits of sun protection, while the second focused on its benefits for skin cancer prevention. Our hypothesis was that the reduction of photoaging would be a more persuasive argument than skin cancer prevention for the adoption of sunscreen use by Hispanic women. Study participants were recruited from beauty salons located in predominantly Hispanic neighborhoods. Each of the two Spanish-language films was approximately 3 min long. A pre-intervention questionnaire assessed subjects' general knowledge and sunscreen habits, and a second questionnaire administered after viewing both films assessed for improvements in risk perception and inquired about which film was more persuasive. Eighty Hispanics participated ranging in age from 19 to 75. The pre-education survey found that 54 out of 80 believed that fair-skin Hispanics (FS) were at risk for skin cancer, and 44 out of 80 believed that dark-skin Hispanics (DS) were at risk. These numbers increased to 72 (FS) and 69 (DS) after the intervention (p value: benefits of sun protection for skin cancer prevention as the more persuasive film (74 out of 80). A Spanish-language video has the potential to make an impact in healthy sun-protective behaviors, and information on how to properly apply sunscreen should be included in educational messages. PMID:24595966

  19. In vivo 3D digital atlas database of the adult C57BL/6J mouse brain by magnetic resonance microscopy

    Directory of Open Access Journals (Sweden)

    Yu Ma

    2008-04-01

    Full Text Available In this study, a 3D digital atlas of the live mouse brain based on magnetic resonance microscopy (MRM is presented. C57BL/6J adult mouse brains were imaged in vivo on a 9.4 Tesla MR instrument at an isotropic spatial resolution of 100 μm. With sufficient signal-to-noise (SNR and contrast-to-noise ratio (CNR, 20 brain regions were identified. Several atlases were constructed including 12 individual brain atlases, an average atlas, a probabilistic atlas and average geometrical deformation maps. We also investigated the feasibility of using lower spatial resolution images to improve time efficiency for future morphological phenotyping. All of the new in vivo data were compared to previous published in vitro C57BL/6J mouse brain atlases and the morphological differences were characterized. Our analyses revealed significant volumetric as well as unexpected geometrical differences between the in vivo and in vitro brain groups which in some instances were predictable (e.g. collapsed and smaller ventricles in vitro but not in other instances. Based on these findings we conclude that although in vitro datasets, compared to in vivo images, offer higher spatial resolutions, superior SNR and CNR, leading to improved image segmentation, in vivo atlases are likely to be an overall better geometric match for in vivo studies, which are necessary for longitudinal examinations of the same animals and for functional brain activation studies. Thus the new in vivo mouse brain atlas dataset presented here is a valuable complement to the current mouse brain atlas collection and will be accessible to the neuroscience community on our public domain mouse brain atlas website.

  20. The effects of feeding with synbiotic (Pediococcus acidilactici and fructooligosaccharide) enriched adult Artemia on skin mucus immune responses, stress resistance, intestinal microbiota and performance of angelfish (Pterophyllum scalare).

    Science.gov (United States)

    Azimirad, Mahmood; Meshkini, Saeed; Ahmadifard, Nasrollah; Hoseinifar, Seyed Hossein

    2016-07-01

    The aim of this study was to evaluate the effects of feeding on synbiotic (Pediococcus acidilactici and fructooligosaccharide) enriched adult Artemia franciscana on skin mucus immune responses, stress resistance, intestinal microbiota and growth performance of angelfish (Pterophyllum scalare). Three hundred and sixty fish with initial weight 3.2 ± 0.13 g were randomly divided into twelve aquaria (50 L) assigned to four groups in triplicates. Fish were fed for 7 weeks with dietary treatments, including treatment 1: feeding adult Artemia without enrichment (control group), treatment 2: feeding adult Artemia enriched with lyophilised probiotic P. acidilactici (700 mg L(-1)), 3: feeding adult Artemia enriched with prebiotic fructooligosaccharide (FOS) (100 mg L(-1)), group 4: feeding adult Artemia enriched with synbiotic (P. acidilactici (700 mg L(-1)) + FOS (100 mg L(-1))). Skin mucus immune responses (lysozyme activity, total Immunoglobulin and protease), stress resistance against environmental stress (acute decrease of temperature and increase salinity), intestinal microbiota as well as growth indices were measured at the end of feeding trial. Artemia enriched with synbiotic significantly improved growth performance compared to other treatments (P < 0.05). The highest weight gain and specific growth rate (SGR) was observed in synbiotic fed fish (P < 0.05). Compared to the other treatments, the population of lactic acid bacteria was significantly higher in the intestinal microbiota of fish fed synbiotic supplemented diet (P < 0.05). In the environmental stress challenge test, the maximum resistance to abrupt decrease of temperature (17 °C) or elevation of salinity (12 g per liter) was observed in the synbiotic treatment. Also, the total immunoglobulin and lysozyme activity level of skin mucus was significantly elevated in fish fed Artemia enriched with synbiotic (P < 0.05). These results revealed that feeding angelfish with synbiotic

  1. Correlation of {sup 32}P-postlabelling-detection of DNA adducts in mouse skin in vivo with the polycyclic aromatic compound content and mutagenicity in Salmonella typhimurium of a range of oil products

    Energy Technology Data Exchange (ETDEWEB)

    Booth, E.D.; Loose, R.W.; Watson, W.P. [Toxicology Department, Shell International Chemicals B.V., Amsterdam (Netherlands); Brandt, H.C.A. [Product Development Department, Shell International Oil Products B.V., Amsterdam (Netherlands)

    1998-07-01

    The in vivo genotoxic activities in mouse skin of the dimethyl sulphoxide (DMSO) extracts of a range of oil products [residual aromatic extract; untreated heavy paraffinic distillate aromatic extract; mildly refined light naphthenic base oil; bitumen (vacuum residue); high viscosity index base oil obtained by catalytic hydrogenation] were evaluated by {sup 32}P-postlabelling DNA analysis. The results of quantitative {sup 32}P-postlabelling analyses of epidermal DNA from mice treated with the DMSO extracts showed linear relationships with the total polycyclic aromatic compound (PAC) contents, determined by the Institute of Petroleum method IP 346 and also the 3-6 ring PAC contents, measured by on-line liquid-liquid extraction using flow injection analysis. The {sup 32}P-postlabelling data also showed a linear relationship with the mutagenicity indices of these oil products determined in S. typhimurium TA98 using the modified Ames Salmonella microsome test. The in vivo genotoxicity of the DMSO extracts from the oil products was low, judged by {sup 32}P-postlabelling analysis of DNA adducts measured in epidermal DNA of treated mouse skin, and ranging from 2 to 723 attomole/{mu}g DNA per mg oil product. The in vivo {sup 32}P-postlabelling data from this study are consistent with these materials expressing low genotoxicity in mouse skin in vivo. The DMSO extraction procedure coupled with {sup 32}P-postlabelling DNA analysis is useful for ranking the relative genotoxic potency in vivo of a wide range of oil products. In general the trend observed is similar to rankings based on physicochemical measurements of total PAC contents or 3-6 ring PAC contents of the oil products. (orig.) With 4 figs., 1 tab., 44 refs.

  2. Correlation of 32P-postlabelling-detection of DNA adducts in mouse skin in vivo with the polycyclic aromatic compound content and mutagenicity in Salmonella typhimurium of a range of oil products

    International Nuclear Information System (INIS)

    The in vivo genotoxic activities in mouse skin of the dimethyl sulphoxide (DMSO) extracts of a range of oil products [residual aromatic extract; untreated heavy paraffinic distillate aromatic extract; mildly refined light naphthenic base oil; bitumen (vacuum residue); high viscosity index base oil obtained by catalytic hydrogenation] were evaluated by 32P-postlabelling DNA analysis. The results of quantitative 32P-postlabelling analyses of epidermal DNA from mice treated with the DMSO extracts showed linear relationships with the total polycyclic aromatic compound (PAC) contents, determined by the Institute of Petroleum method IP 346 and also the 3-6 ring PAC contents, measured by on-line liquid-liquid extraction using flow injection analysis. The 32P-postlabelling data also showed a linear relationship with the mutagenicity indices of these oil products determined in S. typhimurium TA98 using the modified Ames Salmonella microsome test. The in vivo genotoxicity of the DMSO extracts from the oil products was low, judged by 32P-postlabelling analysis of DNA adducts measured in epidermal DNA of treated mouse skin, and ranging from 2 to 723 attomole/μg DNA per mg oil product. The in vivo 32P-postlabelling data from this study are consistent with these materials expressing low genotoxicity in mouse skin in vivo. The DMSO extraction procedure coupled with 32P-postlabelling DNA analysis is useful for ranking the relative genotoxic potency in vivo of a wide range of oil products. In general the trend observed is similar to rankings based on physicochemical measurements of total PAC contents or 3-6 ring PAC contents of the oil products. (orig.)

  3. Eosinophil-derived leukotriene C4 signals via type 2 cysteinyl leukotriene receptor to promote skin fibrosis in a mouse model of atopic dermatitis.

    Science.gov (United States)

    Oyoshi, Michiko K; He, Rui; Kanaoka, Yoshihide; ElKhal, Abdallah; Kawamoto, Seiji; Lewis, Christopher N; Austen, K Frank; Geha, Raif S

    2012-03-27

    Atopic dermatitis (AD) skin lesions exhibit epidermal and dermal thickening, eosinophil infiltration, and increased levels of the cysteinyl leukotriene (cys-LT) leukotriene C(4) (LTC(4)). Epicutaneous sensitization with ovalbumin of WT mice but not ΔdblGATA mice, the latter of which lack eosinophils, caused skin thickening, collagen deposition, and increased mRNA expression of the cys-LT generating enzyme LTC(4) synthase (LTC(4)S). Skin thickening and collagen deposition were significantly reduced in ovalbumin-sensitized skin of LTC(4)S-deficient and type 2 cys-LT receptor (CysLT(2)R)-deficient mice but not type 1 cys-LT receptor (CysLT(1)R)-deficient mice. Adoptive transfer of bone marrow-derived eosinophils from WT but not LTC(4)S-deficient mice restored skin thickening and collagen deposition in epicutaneous-sensitized skin of ΔdblGATA recipients. LTC(4) stimulation caused increased collagen synthesis by human skin fibroblasts, which was blocked by CysLT(2)R antagonism but not CysLT(1)R antagonism. Furthermore, LTC(4) stimulated skin fibroblasts to secrete factors that elicit keratinocyte proliferation. These findings establish a role for eosinophil-derived cys-LTs and the CysLT(2)R in the hyperkeratosis and fibrosis of allergic skin inflammation. Strategies that block eosinophil infiltration, cys-LT production, or the CysLT(2)R might be useful in the treatment of AD.

  4. Characteristics of Adult T-Cell Leukemia/Lymphoma Patients with Long Survival: Prognostic Significance of Skin Lesions and Possible Beneficial Role of Valproic Acid

    Directory of Open Access Journals (Sweden)

    Plumelle Yves

    2015-01-01

    Full Text Available We describe the clinical and biological features of ten patients with a survival superior to ten years (long survival, out of 175 patients diagnosed with Adult T-cell Leukemia/Lymphoma (ATL in Martinique (1983–2013. There were 5 lymphoma and 5 chronic subtypes. Five of them (3 chronic, 2 lymphoma had been treated with valproic acid (VA for neurological disorders developed before or after ATL diagnosis, suggesting a beneficial role for VA as a histone deacetylase inhibitor (HDI in ATL treatment. Total duration of uninterrupted VA treatment ranged from 8 to 37 years. Overall, the 175 incident ATL cases presented with a median survival of 5.43 months. The five VA-treated (VA+ patients presented with longer survival compared to VA treatment-free patients (VA−. For chronic subtypes, survival periods were of 213 months for 3 VA+ patients and of 33 months for 11 VA− patients (p=0.023. For lymphoma subtypes, survival periods were of 144 months for 2 VA+ patients versus 6 months for 49 VA− patients (p=0.0046. ATL cases with skin lesions, particularly lymphoma subtypes, had a longer survival (13.96 months compared to those without skin lesions (6.06 months, p=0.002. Eight out of the 10 patients presenting with long survival had skin lesions.

  5. Long-term administration of scopolamine interferes with nerve cell proliferation, differentiation and migration in adult mouse hippocampal dentate gyrus, but it does not induce cell death

    Institute of Scientific and Technical Information of China (English)

    Bing Chun Yan; Yun Lyul Lee; Il-Jun Kang; Moo-Ho Won; Joon Ha Park; Bai Hui Chen; Jeong-Hwi Cho; In Hye Kim; Ji Hyeon Ahn; Jae-Chul Lee; In Koo Hwang; Jun Hwi Cho

    2014-01-01

    Long-term administration of scopolamine, a muscarinic receptor antagonist, can inhibit the survival of newly generated cells, but its effect on the proliferation, differentiation and migration of nerve cells in the adult mouse hippocampal dentate gyrus remain poorly understood. In this study, we used immunohistochemistry and western blot methods to weekly detect the biological behaviors of nerve cells in the hippocampal dentate gyrus of adult mice that received intraperito-neal administration of scopolamine for 4 weeks. Expression of neuronal nuclear antigen (NeuN;a neuronal marker) and Fluoro-Jade B (a marker for the localization of neuronal degeneration) was also detected. After scopolamine treatment, mouse hippocampal neurons did not die, and Ki-67 (a marker for proliferating cells)-immunoreactive cells were reduced in number and reac hed the lowest level at 4 weeks. Doublecortin (DCX; a marker for newly generated neurons)-im-munoreactive cells were gradually shortened in length and reduced in number with time. After scopolamine treatment for 4 weeks, nearly all of the 5-bromo-2′-deoxyuridine (BrdU)-labeled newly generated cells were located in the subgranular zone of the dentate gyrus, but they did not migrate into the granule cell layer. Few mature BrdU/NeuN double-labeled cells were seen in the subgranular zone of the dentate gyrus. These ifndings suggest that long-term administration of scopolamine interferes with the proliferation, differentiation and migration of nerve cells in the adult mouse hippocampal dentate gyrus, but it does not induce cell death.

  6. Culture and establishment of self-renewing human and mouse adult liver and pancreas 3D organoids and their genetic manipulation.

    Science.gov (United States)

    Broutier, Laura; Andersson-Rolf, Amanda; Hindley, Christopher J; Boj, Sylvia F; Clevers, Hans; Koo, Bon-Kyoung; Huch, Meritxell

    2016-09-01

    Adult somatic tissues have proven difficult to expand in vitro, largely because of the complexity of recreating appropriate environmental signals in culture. We have overcome this problem recently and developed culture conditions for adult stem cells that allow the long-term expansion of adult primary tissues from small intestine, stomach, liver and pancreas into self-assembling 3D structures that we have termed 'organoids'. We provide a detailed protocol that describes how to grow adult mouse and human liver and pancreas organoids, from cell isolation and long-term expansion to genetic manipulation in vitro. Liver and pancreas cells grow in a gel-based extracellular matrix (ECM) and a defined medium. The cells can self-organize into organoids that self-renew in vitro while retaining their tissue-of-origin commitment, genetic stability and potential to differentiate into functional cells in vitro (hepatocytes) and in vivo (hepatocytes and endocrine cells). Genetic modification of these organoids opens up avenues for the manipulation of adult stem cells in vitro, which could facilitate the study of human biology and allow gene correction for regenerative medicine purposes. The complete protocol takes 1-4 weeks to generate self-renewing 3D organoids and to perform genetic manipulation experiments. Personnel with basic scientific training can conduct this protocol. PMID:27560176

  7. Expression of C4.4A, a structural uPAR homolog, reflects squamous epithelial differentiation in the adult mouse and during embryogenesis

    DEFF Research Database (Denmark)

    Kriegbaum, Mette Camilla; Jacobsen, Benedikte; Hald, Andreas;

    2011-01-01

    by a comprehensive immunohistochemical mapping. This task was accomplished by staining paraffin-embedded tissues with a specific rabbit polyclonal anti-C4.4A antibody. In the adult mouse, C4.4A was predominantly expressed in the suprabasal layers of the squamous epithelia of the oral cavity, esophagus, non-glandular...... expression first appears in the developing squamous epithelium at embryonic day 13.5. This anatomical location of C4.4A is thus concordant with a possible functional role in early differentiation of stratified squamous epithelia....

  8. Keratinocyte p38δ loss inhibits Ras-induced tumor formation, while systemic p38δ loss enhances skin inflammation in the early phase of chemical carcinogenesis in mouse skin.

    Science.gov (United States)

    Kiss, Alexi; Koppel, Aaron C; Anders, Joanna; Cataisson, Christophe; Yuspa, Stuart H; Blumenberg, Miroslav; Efimova, Tatiana

    2016-05-01

    p38δ expression and/or activity are increased in human cutaneous malignancies, including invasive squamous cell carcinoma (SCC) and head and neck SCC, but the role of p38δ in cutaneous carcinogenesis has not been well-defined. We have reported that mice with germline loss of p38δ exhibited a reduced susceptibility to skin tumor development compared with wild-type mice in the two-stage 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) chemical skin carcinogenesis model. Here, we report that p38δ gene ablation inhibited the growth of tumors generated from v-ras(Ha) -transformed keratinocytes in skin orthografts to nude mice, indicating that keratinocyte-intrinsic p38δ is required for Ras-induced tumorigenesis. Gene expression profiling of v-ras(Ha) -transformed p38δ-null keratinocytes revealed transcriptional changes associated with cellular responses linked to tumor suppression, such as reduced proliferation and increased differentiation, cell adhesion, and cell communications. Notably, a short-term DMBA/TPA challenge, modeling the initial stages of chemical skin carcinogenesis treatment, elicited an enhanced inflammation in p38δ-null skin compared with skin of wild-type mice, as assessed by measuring the expression of pro-inflammatory cytokines, including IL-1β, IL-6, IL-17, and TNFα. Additionally, p38δ-null skin and p38δ-null keratinocytes exhibited increased p38α activation and signaling in response to acute inflammatory challenges, suggesting a role for p38α in stimulating the elevated inflammatory response in p38δ-null skin during the initial phases of the DMBA/TPA treatment compared with similarly treated p38δ(+/+) skin. Altogether, our results indicate that p38δ signaling regulates skin carcinogenesis not only by keratinocyte cell-autonomous mechanisms, but also by influencing the interaction between between the epithelial compartment of the developing skin tumor and its stromal microenvironment.

  9. Fluorescence photobleaching of ALA and ALA-heptyl ester induced protoporphyrin IX during photodynamic therapy of normal hairless mouse skin: a comparison of two light sources and different illumination schemes.

    Science.gov (United States)

    Pudroma, Xiao; Juzeniene, Asta; Ma, Li-Wei; Iani, Vladimir; Moan, Johan

    2011-01-01

    This study investigated photobleaching of protoporphyrin IX (PpIX) induced by 5-aminolevulinic acid (ALA) and ALA-heptyl ester during superficial photodynamic therapy (PDT) in normal skin of the female BALB/c-nu/nu athymic mouse. We examined the effects of two light sources (laser and broadband lamp) and two different illumination schemes (fractionated light and continuous irradiation) on the kinetics of photobleaching. Our results show that light exposure (0-30 minutes, 10 mW/cm2) of wavelengths of approximately 420 nm (blue light) and 635 nm (red light) induced time-dependent PpIX photobleaching for mouse skin of 2% ALA and ALA-heptyl ester. Blue light (10 mW/cm2) caused more rapid PpIX photobleaching than did red light (100 mW/cm2), which is attributed to stronger absorption at 407 nm than at 632 nm for PpIX. In the case of light fractionation, fractionated light induced faster photobleaching compared with continuous light exposure after topical application of 2% ALA and ALA-heptyl ester in vivo. These have been suggested to allow reoxygenation of the irradiated tissue, with a consequent enhancement of singlet oxygen production in the second and subsequent fractions.

  10. Treatment of radioinduced skin burns by adult stem cells;Traitement des brulures cutanees radio-induites par cellules souches adultes

    Energy Technology Data Exchange (ETDEWEB)

    Lataillade, J.J.; Prat, M. [Hopital Militaire Percy, Centre de Transfusion Sanguine des Armees, Dept. Recherches et Therapies Cellulaires, 92 - Clamart (France); Gourmelon, P. [Institut de Radioprotection et de Surete Nucleaire (IRSN), 92 - Fontenay-aux-Roses (France); Bey, E. [Hopital Militaire Percy, Service de Chirurgie Plastique, 92 - Clamart (France)

    2009-12-15

    In the area of skin injuries caused by ionizing radiations; the recent opportunity give us the the possibility to manage victims of radiation accidents with skin acute symptoms of irradiation. The approach of cell therapy developed for these patients could be in a second time, used for other types of injuries as thermal burns and the injuries linked to overexposure in radiotherapy. In spite of the diversity of approaches of allogeneic and autologous transplantation, the prognosis of deep and extended radioinduced burns is not completely satisfying because of inflammatory recurrences, origin of graft failures. The stem cells have been used in association. The stem cells were got from sampling of autologous bone marrow after an expansion in vitro from 15 to 17 days. The cultures were realised in medium with 8% of platelet lysate (clinical grade). The cells have been given by injection in complement of epidermis auto graft. A spectacular effect was noticed the day after the injection, but disappearing in some days encouraging to realize supplementary injections. An effect of the quickness and the quality of the graft success is appeared significant too. no necrosis recurrence for the patients after four years for the first one of them. We think that the stem cells participate to the local control of inflammation. (N.C.)

  11. Distribution of epidermal growth factor receptors in rat tissues during embryonic skin development, hair formation, and the adult hair growth cycle

    DEFF Research Database (Denmark)

    Green, M R; Couchman, J R

    1984-01-01

    condensates marking the first stage of hair follicle development. This restricted and temporary loss of EGF receptors above these specialized mesenchymal condensates implies a role for the EGF receptor and possibly EGF or an EGF-like ligand in stimulating the epithelial downgrowth required for hair follicle...... on the binding distribution of [125I]EGF, representing the tissue localization of available EGF receptors, during embryonic rat skin development including hair follicle formation and the adult hair growth cycle. At 16 days embryonic development a relatively low receptor density is seen over all the epidermal...... development. In the anagen hair bulb, receptors for EGF are detected over the outer root sheath and the epithelial cell layers at the base of the follicle and show a correlation with the areas of epithelial proliferation in the hair bulb. During the catagen and telogen phases of the hair cycle, receptors...

  12. Tattooing of skin results in transportation and light-induced decomposition of tattoo pigments--a first quantification in vivo using a mouse model.

    Science.gov (United States)

    Engel, Eva; Vasold, Rudolf; Santarelli, Francesco; Maisch, Tim; Gopee, Neera V; Howard, Paul C; Landthaler, Michael; Bäumler, Wolfgang

    2010-01-01

    Millions of people are tattooed with inks that contain azo pigments. The pigments contained in tattoo inks are manufactured for other uses with no established history of safe use in humans and are injected into the skin at high densities (2.5 mg/cm(2)). Tattoo pigments disseminate after tattooing throughout the human body and although some may photodecompose at the injection site by solar or laser light exposure, the extent of transport or photodecomposition under in vivo conditions remains currently unknown. We investigated the transport and photodecomposition of the widely used tattoo Pigment Red 22 (PR 22) following tattooing into SKH-1 mice. The pigment was extracted quantitatively at different times after tattooing. One day after tattooing, the pigment concentration was 186 microg/cm(2) skin. After 42 days, the amount of PR 22 in the skin has decreased by about 32% of the initial value. Exposure of the tattooed skin, 42 days after tattooing, to laser light reduced the amount of PR 22 by about 51% as compared to skin not exposed to laser light. A part of this reduction is as a result of photodecomposition of PR 22 as shown by the detection of corresponding hazardous aromatic amines. Irradiation with solar radiation simulator for 32 days caused a pigment reduction of about 60% and we again assume pigment decomposition in the skin. This study is the first quantitative estimate of the amount of tattoo pigments transported from the skin into the body or decomposed by solar or laser radiation. PMID:19703227

  13. Dermal dysplasia, hypotrichosis, and dorsal skin ulcers in adult NMRI-mice after X-irradiation in utero

    International Nuclear Information System (INIS)

    Prenatal X-irradiation in mice leads to a marked incidence of hypotrichosis and alopecia in offspring, when irradiation occurs during the stage of late organogenesis (day 11-13 p.c.). In addition, severe ulcerative dermatitis occurs in offspring starting at 2 months of age, with marked preference for those animals which have been irradiated at least during days 11-13 p.c. This occurs without any dose dependence; application of doses between 2.4 Gy and 7.2 Gy results in approximately similar incidence rates of skin ulcers (range between 39.1 and 48.0%). There is no sex preference and no dependence on housing. At autopsy no special abnormalities were found in the internal organs with the exception of frequent signs of amyloidosis. This disease pattern could also be produced in germ-free animals. The intracutanous administration of skin extracts from affected animals into unirradiated mice leads to a marked infiltration of leukocytes. It is therefore suggested that prenatal X-irradiation induces a distinct dysplasia of the epidermis, which is followed by an endogenous leukotactic activity. (orig.)

  14. Low back skin sensitivity has minimal impact on active lumbar spine proprioception and stability in healthy adults.

    Science.gov (United States)

    Beaudette, Shawn M; Larson, Katelyn J; Larson, Dennis J; Brown, Stephen H M

    2016-08-01

    The purpose of the current work was to (1) determine whether low back cutaneous sensitivity could be reduced through the use of a topical lidocaine-prilocaine anesthetic (EMLA(®)) to mirror reductions reported in chronic lower back pain (CLBP) patients, as well as to (2) identify whether reductions in cutaneous sensitivity resulted in decreased lumbar spine proprioception, neuromuscular control and dynamic stability. Twenty-eight healthy participants were divided equally into matched EMLA and PLACEBO treatment groups. Groups completed cutaneous minimum monofilament and two-point discrimination (TPD) threshold tests, as well as tests of sagittal and axial lumbar spine active repositioning error, seated balance and repeated lifting dynamic stability. These tests were administered both before and after the application of an EMLA or PLACEBO treatment. Results show that low back minimum monofilament and TPD thresholds were significantly increased within the EMLA group. Skin sensitivity remained unchanged in the PLACEBO group. In the EMLA group, decreases in low back cutaneous sensitivity had minimal effect on low back proprioception (active sagittal and axial repositioning) and dynamic stability (seated balance and repeated lifting). These findings demonstrate that treating the skin of the low back with an EMLA anesthetic can effectively decrease the cutaneous sensitivity of low back region. Further, these decreases in peripheral cutaneous sensitivity are similar in magnitude to those reported in CLBP patients. Within this healthy population, decreased cutaneous sensitivity of the low back region has minimal influence on active lumbar spine proprioception, neuromuscular control and dynamic stability. PMID:27010722

  15. Mouse genetic differences in voluntary wheel running, adult hippocampal neurogenesis and learning on the multi-strain-adapted plus water maze

    Science.gov (United States)

    Merritt, Jennifer; Rhodes, Justin S.

    2014-01-01

    Moderate levels of aerobic exercise broadly enhance cognition throughout the lifespan. One hypothesized contributing mechanism is increased adult hippocampal neurogenesis. Recently, we measured the effects of voluntary wheel running on adult hippocampal neurogenesis in 12 different mouse strains, and found increased neurogenesis in all strains, ranging from 2 to 5 fold depending on the strain. The purpose of this study was to determine the extent to which increased neurogenesis from wheel running is associated with enhanced performance on the water maze for 5 of the 12 strains, chosen based on their levels of neurogenesis observed in the previous study (C57BL/6J, 129S1/SvImJ, B6129SF1/J, DBA/2J, and B6D2F1/J). Mice were housed with or without a running wheels for 30 days then tested for learning and memory on the plus water maze, adapted for multiple strains, and rotarod test of motor performance. The first 10 days, animals were injected with BrdU to label dividing cells. After behavioral testing animals were euthanized to measure adult hippocampal neurogenesis using standard methods. Levels of neurogenesis depended on strain but all mice had a similar increase in neurogenesis in response to exercise. All mice acquired the water maze but performance depended on strain. Exercise improved water maze performance in all strains to a similar degree. Rotarod performance depended on strain. Exercise improved rotarod performance only in DBA/2J and B6D2F1/J mice. Taken together, results demonstrate that despite different levels of neurogenesis, memory performance and motor coordination in these mouse strains, all strains have the capacity to increase neurogenesis and improve learning on the water maze through voluntary wheel running. PMID:25435316

  16. Morphological classification of nuchal skin in human fetuses with trisomy 21, 18, and 13 at 12-18 weeks and in a trisomy 16 mouse.

    Science.gov (United States)

    von Kaisenberg, C S; Krenn, V; Ludwig, M; Nicolaides, K H; Brand-Saberi, B

    1998-02-01

    An increase in the nuchal translucency that can be detected at 10-14 weeks of gestation by ultrasound forms the basis for a screening test for chromosomal abnormality. Several mechanisms leading to this increase in skin thickness have been proposed, including changes of the extracellular matrix, cardiac defects and abnormalities of the large vessels. This study examines the composition of the extracellular matrix of the skin in gestational age-matched fetuses with trisomy 21, 18 and 13 from 12-18 weeks. Immunohistochemistry was applied with monoclonal and polyclonal antibodies against collagen type I, III, IV, V and VI and against laminin and fibronectin. Collagen type VI gene expression was further studied by in situ hybridization to detect differences in expression patterns of COL6A1, COL6A3 and COL1A1 between normal fetuses and those with trisomy 21. The ultrastructure of tissue samples was studied by transmission electron microscopy (TEM) and additionally by immunogold TEM. Further, we examined the morphology of the skin in an animal model for Down's syndrome, the murine trisomy 16, by light and TEM. The dermis of trisomy 21 fetuses was richer in collagen type VI than that of normal fetuses and other trisomies, and COL6A1, located on chromosome 21, was expressed in a wider area than COL6A3, which is located on chromosome 2. Collagen type I was less abundant in the skin of trisomy 18 fetuses, while the skin of all three trisomies contained a dense network of collagen type III and V in comparison with normal fetuses. Collagen type IV, of which two genes are located on chromosome 13, was expressed in the basement membranes of the skin in all fetuses and additionally in the dermal fibroblasts only of trisomy 13 fetuses. Likewise, laminin was present in all basement membranes of normal and trisomic fetuses as well as in dermal fibroblasts of fetuses with trisomy 18. LAMA1 and LAMA3 genes are located on chromosome 18. Dermal cysts were found in the skin of trisomy 18

  17. Cytochrome P450 1b1 in polycyclic aromatic hydrocarbon (PAH)-induced skin carcinogenesis: Tumorigenicity of individual PAHs and coal-tar extract, DNA adduction and expression of select genes in the Cyp1b1 knockout mouse.

    Science.gov (United States)

    Siddens, Lisbeth K; Bunde, Kristi L; Harper, Tod A; McQuistan, Tammie J; Löhr, Christiane V; Bramer, Lisa M; Waters, Katrina M; Tilton, Susan C; Krueger, Sharon K; Williams, David E; Baird, William M

    2015-09-01

    FVB/N mice wild-type, heterozygous or null for Cyp 1b1 were used in a two-stage skin tumor study comparing PAH, benzo[a]pyrene (BaP), dibenzo[def,p]chrysene (DBC), and coal tar extract (CTE, SRM 1597a). Following 20 weeks of promotion with TPA the Cyp 1b1 null mice, initiated with DBC, exhibited reductions in incidence, multiplicity, and progression. None of these effects were observed with BaP or CTE. The mechanism of Cyp 1b1-dependent alteration of DBC skin carcinogenesis was further investigated by determining expression of select genes in skin from DBC-treated mice 2, 4 and 8h post-initiation. A significant reduction in levels of Cyp 1a1, Nqo1 at 8h and Akr 1c14 mRNA was observed in Cyp 1b1 null (but not wt or het) mice, whereas no impact was observed in Gst a1, Nqo 1 at 2 and 4h or Akr 1c19 at any time point. Cyp 1b1 mRNA was not elevated by DBC. The major covalent DNA adducts, dibenzo[def,p]chrysene-(±)-11,12-dihydrodiol-cis and trans-13,14-epoxide-deoxyadenosine (DBCDE-dA) were quantified by UHPLC-MS/MS 8h post-initiation. Loss of Cyp1 b1 expression reduced DBCDE-dA adducts in the skin but not to a statistically significant degree. The ratio of cis- to trans-DBCDE-dA adducts was higher in the skin than other target tissues such as the spleen, lung and liver (oral dosing). These results document that Cyp 1b1 plays a significant role in bioactivation and carcinogenesis of DBC in a two-stage mouse skin tumor model and that loss of Cyp 1b1 has little impact on tumor response with BaP or CTE as initiators. PMID:26049101

  18. Preparation of studies on antibody production against food allergens in mice and effect of flavonoids in simultaneous injection into mouse skin.

    Science.gov (United States)

    We had tried to evaluate antibody production against food allergens in mouse models. Some food allergens, which were beta-lactoglobulin, ovalbumin, and peanut allergen Ara h 1, were used as immunoges in this experiment. Under the same conditions these allergens were immunized as emulsion with freund...

  19. Protease-activated receptor-1 negatively regulates proliferation of neural stem/progenitor cells derived from the hippocampal dentate gyrus of the adult mouse.

    Science.gov (United States)

    Tanaka, Masayuki; Yoneyama, Masanori; Shiba, Tatsuo; Yamaguchi, Taro; Ogita, Kiyokazu

    2016-07-01

    Thrombin-activated protease-activated receptor (PAR)-1 regulates the proliferation of neural cells following brain injury. To elucidate the involvement of PAR-1 in the neurogenesis that occurs in the adult hippocampus, we examined whether PAR-1 regulated the proliferation of neural stem/progenitor cells (NPCs) derived from the murine hippocampal dentate gyrus. NPC cultures expressed PAR-1 protein and mRNA encoding all subtypes of PAR. Direct exposure of the cells to thrombin dramatically attenuated the cell proliferation without causing cell damage. This thrombin-induced attenuation was almost completely abolished by the PAR antagonist RWJ 56110, as well as by dabigatran and 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF), which are selective and non-selective thrombin inhibitors, respectively. Expectedly, the PAR-1 agonist peptide (AP) SFLLR-NH2 also attenuated the cell proliferation. The cell proliferation was not affected by the PAR-1 negative control peptide RLLFT-NH2, which is an inactive peptide for PAR-1. Independently, we determined the effect of in vivo treatment with AEBSF or AP on hippocampal neurogenesis in the adult mouse. The administration of AEBSF, but not that of AP, significantly increased the number of newly-generated cells in the hippocampal subgranular zone. These data suggest that PAR-1 negatively regulated adult neurogenesis in the hippocampus by inhibiting the proliferative activity of the NPCs. PMID:27426918

  20. A Comparison between the Colony Formation of Adult Mouse Spermatogonial Stem Cells in Co cultures with Sertoli and STO (Mouse Embryonic Fibroblast Cell Line

    Directory of Open Access Journals (Sweden)

    Seyed Morteza Koruji

    2010-01-01

    Full Text Available Objective: The aim of this study was to compare the colony formation of spermatogonialstem cells (SSCs on sertoli and STO (Mouse embryonic fibroblast cell line feeder celllayers during a two-week period.Materials and Methods: Initially, sertoli cells and SSCs were isolated from adultmouse testes using a two-step enzymatic digestion and lectin immobilization. Characteristicsof the isolated cells were immunocytochemically confirmed by examiningfor the presence of Oct-4, CDH1, promyelocytic leukaemia zinc finger factor (PLZF,SSC C-kit, and the distribution of Sertoli cell vimentin. SSCs were then cultured abovethe Sertoli, STO and the control (without co-culture separately for two weeks. In allthree groups, the number and diameter of colonies were evaluated using an invert microscopeon the 3rd, 7th, 10th and 14th day. β1 and α6-integrin m-RNA expressions wereassessed using a reverse transcription polymerase chain reaction (RT-PCR and realtimePCR. Furthermore, Oct-4 m RNA expression was assessed using real time PCR.Statistical analysis was performed using ANOVA; and the paired two-sample t test andTukey’s test were used as post-hoc tests for the data analysis of the three sertoli, STOand control cocultures.Results: At the four specified time points, our results showed significant differences (p<0.05in colony numbers and diameters among the sertoli, STO and control groups. The numberand diameter of colonies increased more rapidly in the sertoli coculture than in the othertwo Our results at all four time points also showed significant differences (p<0.05 in themean colony numbers and diameters between the three groups, with the Sertoli coculturehaving the highest mean values for colony numbers and diameters. The RT-PCR results,after two-weeks of culturing, showed that β1-integrin was expressed in all three groups cocultures,but α6-integrin was not expressed. Additionally, based on real time PCR results,the three genes (β1-integrin, α6-integrin

  1. The clinical utility of tuberculin skin test and interferon-γ release assay in the diagnosis of active tuberculosis among young adults: a prospective observational study

    Directory of Open Access Journals (Sweden)

    Lee Sei Won

    2011-04-01

    Full Text Available Abstract Background The roles of the tuberculin skin test (TST and QuantiFERON®-TB Gold In-Tube assay (QFT-IT in the diagnosis of active tuberculosis (TB are not clear in young adults. We evaluated the diagnostic accuracy of the TST and QFT-IT in smear-negative TB among young adults with no underlying disease. Methods We prospectively enrolled 166 young participants 20-29 years of age with suspected active TB in a military hospital of South Korea. The TST and QFT-IT were performed for all participants. Results Of the 143 patients included in the analysis, active TB was diagnosed in 100 (69.9%. There were 141 male patients, none of whom had immunosuppressive disease. The sensitivity, specificity, positive predictive value (PPV, and negative predictive value (NPV of TST were 94% (95% CI, 87-98%, 88% (95% CI, 74-96%, 95% (95% CI, 88-98%, and 86% (95% CI, 72-94%, respectively. The sensitivity, specificity, PPV, and NPV of the QFT-IT were 93% (95% CI, 86-97%, 95% (95% CI, 81-99%, 98% (95% CI, 92-99%, and 84% (95% CI, 69-93%, respectively. No significant differences were found between the TST and QFT-IT in any statistic. Conclusions Both the TST and QFT-IT showed high sensitivity and specificity in differentiating active TB from other diseases. The diagnostic accuracy of these two tests did not differ significantly when applied to this clinical population of young, immunocompetent adults in whom neonatal BCG vaccination was common, there was no history of previous TB and in whom suspicion of TB was high. Trial registration ClinicalTrials.gov: NCT00982969

  2. Conditional transgenic expression of fibroblast growth factor 9 in the adult mouse heart reduces heart failure mortality after myocardial infarction

    OpenAIRE

    Korf-Klingebiel, Mortimer; Kempf, Tibor; Schlüter, Klaus-Dieter; Willenbockel, Christian; Brod, Torben; Heineke, Jörg; Volker J Schmidt; Jantzen, Franziska; Ralf P Brandes; Sugden, Peter H.; Drexler, Helmut; Molkentin, Jeffery D.; Wollert, Kai C.

    2011-01-01

    BACKGROUND: Fibroblast growth factor 9 (FGF9) is secreted from bone marrow cells, which have been shown to improve systolic function after myocardial infarction (MI) in a clinical trial. FGF9 promotes cardiac vascularization during embryonic development but is only weakly expressed in the adult heart. METHODS AND RESULTS: We used a tetracycline-responsive binary transgene system based on the α-myosin heavy chain promoter to test whether conditional expression of FGF9 in the adult myocardiu...

  3. EXPERIMENTAL STUDY IN DIFFERENT EXPRESSION AND ORGANIZATION OF COLLAGEN IN SKIN WOUNDS OF ADULT AND FETAL RATS

    Institute of Scientific and Technical Information of China (English)

    崔磊; 张群; 钱云良

    2000-01-01

    ReSllm6 Objectif Observer la distribution en espece et dans ie temps du collag&ne dans ies plaies cutals chez ies ratsfretaux et ies rats adultes. methaeS In coloration de van Gieson, moyen stwifique pour ie collagsne, a ate utiliSde pour examiner l' expreSsion et i' organimtion de la dispeition du collagsne. ho matches d' immu~histChchimie et d' hybridetion insitu furent aPPliqudes pour observer la localimtion du mptide et de "tARN dans ie suivi temporal durant la gUdrison des Plaies.Anultats COllagbne de ...

  4. Development of a mouse model for Hutchinson-Gilford progeria syndrome reveal defects in adult stem cell maintenance

    OpenAIRE

    Rosengardten, Ylva

    2011-01-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a very rare genetic disease that presents some features of accelerated aging. Children with the disease are born appearing healthy but start to develop signs of the disease within their first years of life. The disease affects multiple tissues, and the symptoms include growth retardation, alopecia, lack of subcutaneous fat, scleroderma-like skin changes, bone abnormalities and joint stiffness. Heart disease and other atheroscleroti...

  5. On-Going Frontal Alpha Rhythms Are Dominant in Passive State and Desynchronize in Active State in Adult Gray Mouse Lemurs.

    Science.gov (United States)

    Infarinato, Francesco; Rahman, Anisur; Del Percio, Claudio; Lamberty, Yves; Bordet, Regis; Richardson, Jill C; Forloni, Gianluigi; Drinkenburg, Wilhelmus; Lopez, Susanna; Aujard, Fabienne; Babiloni, Claudio; Pifferi, Fabien

    2015-01-01

    The gray mouse lemur (Microcebus murinus) is considered a useful primate model for translational research. In the framework of IMI PharmaCog project (Grant Agreement n°115009, www.pharmacog.org), we tested the hypothesis that spectral electroencephalographic (EEG) markers of motor and locomotor activity in gray mouse lemurs reflect typical movement-related desynchronization of alpha rhythms (about 8-12 Hz) in humans. To this aim, EEG (bipolar electrodes in frontal cortex) and electromyographic (EMG; bipolar electrodes sutured in neck muscles) data were recorded in 13 male adult (about 3 years) lemurs. Artifact-free EEG segments during active state (gross movements, exploratory movements or locomotor activity) and awake passive state (no sleep) were selected on the basis of instrumental measures of animal behavior, and were used as an input for EEG power density analysis. Results showed a clear peak of EEG power density at alpha range (7-9 Hz) during passive state. During active state, there was a reduction in alpha power density (8-12 Hz) and an increase of power density at slow frequencies (1-4 Hz). Relative EMG activity was related to EEG power density at 2-4 Hz (positive correlation) and at 8-12 Hz (negative correlation). These results suggest for the first time that the primate gray mouse lemurs and humans may share basic neurophysiologic mechanisms of synchronization of frontal alpha rhythms in awake passive state and their desynchronization during motor and locomotor activity. These EEG markers may be an ideal experimental model for translational basic (motor science) and applied (pharmacological and non-pharmacological interventions) research in Neurophysiology. PMID:26618512

  6. On-Going Frontal Alpha Rhythms Are Dominant in Passive State and Desynchronize in Active State in Adult Gray Mouse Lemurs.

    Directory of Open Access Journals (Sweden)

    Francesco Infarinato

    Full Text Available The gray mouse lemur (Microcebus murinus is considered a useful primate model for translational research. In the framework of IMI PharmaCog project (Grant Agreement n°115009, www.pharmacog.org, we tested the hypothesis that spectral electroencephalographic (EEG markers of motor and locomotor activity in gray mouse lemurs reflect typical movement-related desynchronization of alpha rhythms (about 8-12 Hz in humans. To this aim, EEG (bipolar electrodes in frontal cortex and electromyographic (EMG; bipolar electrodes sutured in neck muscles data were recorded in 13 male adult (about 3 years lemurs. Artifact-free EEG segments during active state (gross movements, exploratory movements or locomotor activity and awake passive state (no sleep were selected on the basis of instrumental measures of animal behavior, and were used as an input for EEG power density analysis. Results showed a clear peak of EEG power density at alpha range (7-9 Hz during passive state. During active state, there was a reduction in alpha power density (8-12 Hz and an increase of power density at slow frequencies (1-4 Hz. Relative EMG activity was related to EEG power density at 2-4 Hz (positive correlation and at 8-12 Hz (negative correlation. These results suggest for the first time that the primate gray mouse lemurs and humans may share basic neurophysiologic mechanisms of synchronization of frontal alpha rhythms in awake passive state and their desynchronization during motor and locomotor activity. These EEG markers may be an ideal experimental model for translational basic (motor science and applied (pharmacological and non-pharmacological interventions research in Neurophysiology.

  7. Adult mouse motor units develop almost all of their force in the subprimary range: a new all-or-none strategy for force recruitment?

    Science.gov (United States)

    Manuel, Marin; Heckman, C J

    2011-10-19

    Classical studies of the mammalian neuromuscular system have shown an impressive adaptation match between the intrinsic properties of motoneurons and the contractile properties of their motor units. In these studies, the rate at which motoneurons start to fire repetitively corresponds to the rate at which individual twitches start to sum, and the firing rate increases linearly with the amount of excitation ("primary range") up to the point where the motor unit develops its maximal force. This allows for the gradation of the force produced by a motor unit by rate modulation. In adult mouse motoneurons, however, we recently described a regime of firing ("subprimary range") that appears at lower excitation than what is required for the primary range, a finding that might challenge the classical conception. To investigate the force production of mouse motor units, we simultaneously recorded, for the first time, the motoneuron discharge elicited by intracellular ramps of current and the force developed by its motor unit. We showed that the motor unit developed nearly its maximal force during the subprimary range. This was found to be the case regardless of the input resistance of the motoneuron, the contraction speed, or the tetanic force of the motor unit. Our work suggests that force modulation in small mammals mainly relies on the number of motor units that are recruited rather than on rate modulation of individual motor units.

  8. Glial cell line-derived neurotrophic factor alters the growth characteristics and genomic imprinting of mouse multipotent adult germline stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Yoon Hee [Department of Bioscience and Biotechnology, Bio-Organ Research Center/Animal Resources Research Center, Konkuk University, Hwayang-dong, Gwangjin-Gu, Seoul 143 701 (Korea, Republic of); Gupta, Mukesh Kumar, E-mail: goops@konkuk.ac.kr [Department of Animal Biotechnology, Bio-Organ Research Center/Animal Resources Research Center, Konkuk University, Hwayang-dong, Gwangjin-Gu, Seoul 143 701 (Korea, Republic of); Oh, Shin Hye [Department of Bioscience and Biotechnology, Bio-Organ Research Center/Animal Resources Research Center, Konkuk University, Hwayang-dong, Gwangjin-Gu, Seoul 143 701 (Korea, Republic of); Uhm, Sang Jun [Department of Animal Biotechnology, Bio-Organ Research Center/Animal Resources Research Center, Konkuk University, Hwayang-dong, Gwangjin-Gu, Seoul 143 701 (Korea, Republic of); Lee, Hoon Taek, E-mail: htl3675@konkuk.ac.kr [Department of Bioscience and Biotechnology, Bio-Organ Research Center/Animal Resources Research Center, Konkuk University, Hwayang-dong, Gwangjin-Gu, Seoul 143 701 (Korea, Republic of); Department of Animal Biotechnology, Bio-Organ Research Center/Animal Resources Research Center, Konkuk University, Hwayang-dong, Gwangjin-Gu, Seoul 143 701 (Korea, Republic of)

    2010-03-10

    This study evaluated the essentiality of glial cell line-derived neurotrophic factor (GDNF) for in vitro culture of established mouse multipotent adult germline stem (maGS) cell lines by culturing them in the presence of GDNF, leukemia inhibitory factor (LIF) or both. We show that, in the absence of LIF, GDNF slows the proliferation of maGS cells and result in smaller sized colonies without any change in distribution of cells to different cell-cycle stages, expression of pluripotency genes and in vitro differentiation potential. Furthermore, in the absence of LIF, GDNF increased the expression of male germ-line genes and repopulated the empty seminiferous tubule of W/W{sup v} mutant mouse without the formation of teratoma. GDNF also altered the genomic imprinting of Igf2, Peg1, and H19 genes but had no effect on DNA methylation of Oct4, Nanog and Stra8 genes. However, these effects of GDNF were masked in the presence of LIF. GDNF also did not interfere with the multipotency of maGS cells if they are cultured in the presence of LIF. In conclusion, our results suggest that, in the absence of LIF, GDNF alters the growth characteristics of maGS cells and partially impart them some of the germline stem (GS) cell-like characteristics.

  9. Nail psoriasis in an adult successfully treated with a series of herbal skin care products family – a case report.

    Science.gov (United States)

    Tirant, M; Hercogovấ, J; Fioranelli, M; Gianfaldoni, S; Chokoeva, A A; Tchernev, G; Wollina, U; Novotny, F; Roccia, M G; Maximov, G K; França, K; Lotti, T

    2016-01-01

    Psoriasis is a common chronic inflammatory dermatosis that causes significant distress and morbidity. Approximately 50% of patients with cutaneous psoriasis and 90% of patients with psoriatic arthritis demonstrate nail involvement of their psoriasis. Left untreated, nail psoriasis may progress to debilitating nail disease that leads to not only impairment of function but also on quality of life. We report the case of a 50-year-old male patient with recalcitrant nail dystrophies on the fingers since the age of 40, who responded successfully to Dr. Michaels® product family. The patient had a 35-year history of plaque psoriasis localised on the scalp, ears, groin, limbs, and trunk and with psoriatic arthritis. The nail symptoms consisted of onycholysis, onychomycosis, leukonychia, transverse grooves, nail plate crumbling and paronychia of the periungal skin. This case represents the efficacy and safety of the Dr. Michaels® (Soratinex® and Nailinex®) product family with successful resolution of nail dystrophies and surrounding paronychia with no reported adverse events. PMID:27498654

  10. Co-expression of sCD40LIg and CTLA4Ig mediated by adenovirus prolonged mouse skin allograft survival

    Institute of Scientific and Technical Information of China (English)

    LI Zhao-lun; TIAN Pu-xun; XUE Wu-jun; WU Jun

    2006-01-01

    Objective: To investigate the role of simultaneous blockade of CD40/CD40L and B7/CD28 pathways in the immune tolerance via co-expression of sCD40LIg and CTLA4Ig mediated by replication-defective adenovirus. Methods: Ad-sCD40LIgIRES2-CTLA4Ig, replication-defective adenovirus co-expressing sCD40LIg and CTLA4Ig, was constructed and identified. The co-expression of sCD40LIg and CTLA4Ig was evaluated with confocal laser scanning microscope and Western blotting. Skin transplantations of C57BL/6 to BALB/c mice were performed. PBS, Ad-Shuttle-CMV and Ad-sCD40LIg-IRES2-CTLA4Ig were administered. Skin graft survival was monitored and the mRNA expression of both genes was evaluated in the skin allografts.Results: Ad-sCD40LIg-IRES2-CTLA4Ig was constructed successfully and identified. The co-expression of sCD40LIg and CTLA4Ig was identified with confocal laser scanning microscopy and Western blotting. Compared to the skin graft mean survival time (MST) of non-treated group ((5.75±0.71) d) or Ad-Shuttle-CMV-treated group ((5.50±0.53) d), the skin graft MST was dramatically prolonged in the Ad-sCD40LIg-IRES2-CTLA4Ig-treated group (( 16.38± 1.19) d, P<0.001). The mRNA expression of both genes was detected. Conclusion: Ad-sCD40LIg-IRES2-CTLA4Ig, a replication-defective adenovirus carrying genes encoding sCD40LIg and CTLA4Ig, was constructed. Simultaneous blockade of CD40/CD40L and B7/CD28 costimulatory pathway mediated by replication-defective adenovirus significantly prolonged skin allograft survival in mice.

  11. Specific distribution of the autophagic protein GABARAPL1/GEC1 in the developing and adult mouse brain and identification of neuronal populations expressing GABARAPL1/GEC1.

    Directory of Open Access Journals (Sweden)

    Jaclyn Nicole Le Grand

    Full Text Available Macroautophagy is a highly conserved cellular degradation process, regulated by autophagy-related (atg factors, in which a double membrane autophagosome engulfs cytoplasmic components to target them for degradation. In yeast, the Atg8 protein is indispensable for autophagosome formation. In mammals, this is complicated by the presence of six Atg8 homologues grouped into the GABARAP and MAP1LC3 subfamilies. Although these proteins share a high similarity, their transcript expression, regulation and protein interactions differ, suggesting they may display individual properties and specific functions. GABARAPL1/GEC1 is a member of the GABARAP subfamily and its mRNA is the most highly expressed Atg8 homologue in the central nervous system. Consequently, we performed an in depth study of GABARAPL1 distribution in the developing and adult murine brain. Our results show that GABARAPL1 brain expression is visible as early as embryonic day 11 and progressively increases to a maximum level in the adult. Immunohistochemical staining was detected in both fibers and immature neurons in embryos but was restrained to neurons in adult tissue. By E17, intense punctate-like structures were visible and these accumulated in cortical primary neurons treated with the autophagosome/lysosome fusion inhibitor Bafilomycin A1 (Baf A1, suggesting that they represent autophagosomes. Finally, GABARAPL1 expression was particularly intense in motoneurons in the embryo and in neurons involved in somatomotor and neuroendocrine functions in the adult, particularly in the substantia nigra pars compacta, a region affected in Parkinson's disease. Our study of cerebral GABARAPL1 protein expression provides insight into its role in the development and homeostasis of the mouse brain.

  12. Combinatorial chemopreventive effect of butyric acid, nicotinamide and calcium glucarate against the 7,12-dimethylbenz(a)anthracene induced mouse skin tumorigenesis attained by enhancing the induction of intrinsic apoptotic events.

    Science.gov (United States)

    Tiwari, Prakash; Sahay, Satya; Pandey, Manuraj; Qadri, Syed S Y H; Gupta, Krishna P

    2015-01-25

    We explored the basis of the combinatorial chemopreventive effect of butyric acid (BA), nicotinamide (NA) and calcium glucarate (CAG) on mouse skin exposed to 7,12-dimethylbenz(a)anthracene (DMBA). We studied the effects of topical application of DMBA in the presence or absence of BA, NA and CAG on the regulators of apoptosis. DMBA treatment suppressed Bax, Bax/Bcl-2 ratio, release of cyt c, Apaf1, caspase-9, -3 mediated apoptosis. Downregulation of p21 and upregulation of Bcl-2, mut p53 were also observed in only DMBA treated mice. Simultaneous application of BA, NA and CAG induced a mitochondria-mediated apoptosis, characterized by a rise in the Bax, Bax/Bcl-2 ratio, release of cyt c, upregulation of Apaf1 with down-stream activation of caspase-9, -3. Furthermore treatment with BA, NA and CAG demonstrated an upregulation of p21 and downregulation of Bcl-2, mut p53. But this effect was enhanced in the presence of all the three compounds together in combination. Chemoprevention by a combination of BA, NA and CAG by inducing the apoptosis, the natural cell death, suggest the importance of the potential combinational strategies capable of preventing skin tumor development.

  13. Combinatorial chemopreventive effect of butyric acid, nicotinamide and calcium glucarate against the 7,12-dimethylbenz(a)anthracene induced mouse skin tumorigenesis attained by enhancing the induction of intrinsic apoptotic events.

    Science.gov (United States)

    Tiwari, Prakash; Sahay, Satya; Pandey, Manuraj; Qadri, Syed S Y H; Gupta, Krishna P

    2015-01-25

    We explored the basis of the combinatorial chemopreventive effect of butyric acid (BA), nicotinamide (NA) and calcium glucarate (CAG) on mouse skin exposed to 7,12-dimethylbenz(a)anthracene (DMBA). We studied the effects of topical application of DMBA in the presence or absence of BA, NA and CAG on the regulators of apoptosis. DMBA treatment suppressed Bax, Bax/Bcl-2 ratio, release of cyt c, Apaf1, caspase-9, -3 mediated apoptosis. Downregulation of p21 and upregulation of Bcl-2, mut p53 were also observed in only DMBA treated mice. Simultaneous application of BA, NA and CAG induced a mitochondria-mediated apoptosis, characterized by a rise in the Bax, Bax/Bcl-2 ratio, release of cyt c, upregulation of Apaf1 with down-stream activation of caspase-9, -3. Furthermore treatment with BA, NA and CAG demonstrated an upregulation of p21 and downregulation of Bcl-2, mut p53. But this effect was enhanced in the presence of all the three compounds together in combination. Chemoprevention by a combination of BA, NA and CAG by inducing the apoptosis, the natural cell death, suggest the importance of the potential combinational strategies capable of preventing skin tumor development. PMID:25478867

  14. Modulation of miR-203 and its regulators as a function of time during the development of 7, 12 dimethylbenz [a] anthracene induced mouse skin tumors in presence or absence of the antitumor agents.

    Science.gov (United States)

    Tiwari, Prakash; Gupta, Krishna P

    2014-07-15

    We investigated the chemopreventive effects of naturally occurring compounds like butyric acid (BA), nicotinamide (NA) and calcium glucarate (CAG) individually or in combination in 7, 12-dimethylbenz [a] anthracene (DMBA) treated mouse skin at 4 and 16 weeks, the time before and after the tumor development. DMBA application did not show any skin tumors at 4 weeks but well defined tumors appeared at 16 weeks. BA, NA or CAG prevented the tumor development significantly but the protection was highly enhanced when all these compounds were given together. In order to see the molecular changes progressing with tumors, we showed the downregulation of tumor suppressor miR-203 at 16 weeks and upregulation of histone deacetylases (HDAC), DNA methyltransferase, promoter methylation of miR-203 at 4 or 16 weeks. Regulators of micro RNA biogenesis such as DICER1 and Ago2 were also deregulated by DMBA. Proto-oncogene c-myc and BMI1 were upregulated and tumor suppressor gene p16 was downregulated by DMBA as a function of time. Effects of BA, NA or CAG were more pronounced after 16 weeks as compared to 4 weeks in preventing the tumor development and altered gene expression. Concomitant administration of BA, NA and CAG tried to prevent these alterations more effectively than that of individual compound possibly by regulating miR-203 status through epigenetic or biogenetic modulations before and after the tumor development. Study provides a rationale for chemoprevention by combination of different compounds targeting miR-203. PMID:24792773

  15. Conditional deletion of Ccm2 causes hemorrhage in the adult brain: a mouse model of human cerebral cavernous malformations

    OpenAIRE

    Cunningham, Kirk; Uchida, Yutaka; O'Donnell, Erin; Claudio, Estefania; Li, Wenling; Soneji, Kosha; Wang, Hongshan; Mukouyama, Yoh-suke; Siebenlist, Ulrich

    2011-01-01

    Cerebral cavernous malformations (CCM) are irregularly shaped and enlarged capillaries in the brain that are prone to hemorrhage, resulting in headaches, seizures, strokes and even death in patients. The disease affects up to 0.5% of the population and the inherited form has been linked to mutations in one of three genetic loci, CCM1, CCM2 and CCM3. To understand the pathophysiology underlying the vascular lesions in CCM, it is critical to develop a reproducible mouse genetic model of this di...

  16. Preventive effects of butyric acid, nicotinamide, calcium glucarate alone or in combination during the 7, 12-dimethylbenz (a) anthracene induced mouse skin tumorigenesis via modulation of K-Ras-PI3K-AKTpathway and associated micro RNAs.

    Science.gov (United States)

    Tiwari, Prakash; Sahay, Satya; Pandey, Manuraj; Qadri, Syed S Y H; Gupta, Krishna P

    2016-02-01

    Skin cancer is among the most common cancers worldwide and identifiable molecular changes for early and late stage of skin tumorigenesis can suggest the better targets for its control. In this study, we investigated the status of K-Ras-PI3K-AKTpathway followed by NF-κB, cyclin D1, MMP-9 and regulatory micro RNA during 7, 12-dimethylbenz[a]anthracene (DMBA) induced mouse skin tumorigenesis and its prevention by butyric acid (BA), nicotinamide (NA) and calcium glucarate (CAG), individually or in combination with respect to time. DMBA upregulated the K-Ras, PI3K, Akt, NF-κB, cyclin D1 and MMP-9, but downregulated the PTEN in a time dependent manner. DMBA also reduced the levels of micoRNA let-7a but induced the levels of miR-21 and miR-20a as a function of time. BA, NA and CAG were found to prevent DMBA induced changes, but they were most effective when used together in a combination. Reduced let-7a and miR-211 were correlated with the overexpression of K-Ras and MMP-9. Overexpression of miR-21 and miR-20a was correlated with the down regulation of PTEN and overexpression of Cyclin D1. Collectively, the enhanced chemopreventive potential of natural compound in combination via regulation of K-Ras-PI3K-AKTpathway along with regulatory micro RNAs provide a newer and effective mean for cancer management.

  17. UVB exposure enhanced benzanthrone-induced inflammatory responses in SKH-1 mouse skin by activating the expression of COX-2 and iNOS through MAP kinases/NF-κB/AP-1 signalling pathways.

    Science.gov (United States)

    Abbas, Sabiya; Alam, Shamshad; Pal, Anu; Kumar, Mahadeo; Singh, Dhirendra; Ansari, Kausar Mahmood

    2016-10-01

    This study was conducted to explore the role of UVB on benzanthrone (BA)-induced skin inflammation and its mechanism/s. SKH-1 hairless mice were topically exposed with BA (25 and 50 mg/kg b.wt) either alone or along with UVB (50 mJ/cm(2)) for 24 h and estimation of ROS, histopathological analysis, myeloperoxidase (MPO) activity, mast cell staining, immunohistochemistry for COX-2 and iNOS as well as western blotting for MAPKs, p-NF-κB, c-jun, c-fos COX-2 and iNOS were carried out. Enhanced ROS generation, increased epidermal thickness, mast cell number, MPO activity, enhanced expression of COX-2 and iNOS, MAPKs, c-jun, c-fos, NF-κB were found in BA either alone or when followed by UVB treatment, compared to the control groups. Expression of COX-2, iNOS and phosphorylation of ERK1/2 were found to be more enhanced in BA and UVB- exposed group compared to BA and UVB only group, while phosphorylation of JNK1/2, p38, NF-κB and expression of c-jun and c-fos were comparable with BA and UVB only groups. In summary, we suggest that UVB exposure enhanced BA-induced SKH-1 skin inflammation possibly via oxidative stress-mediated activation of MAPKs-NF-κB/AP-1 signalling, which subsequently increased the expression of COX-2 and iNOS and led to inflammation in SKH-1 mouse skin.

  18. Preventive effects of butyric acid, nicotinamide, calcium glucarate alone or in combination during the 7, 12-dimethylbenz (a) anthracene induced mouse skin tumorigenesis via modulation of K-Ras-PI3K-AKTpathway and associated micro RNAs.

    Science.gov (United States)

    Tiwari, Prakash; Sahay, Satya; Pandey, Manuraj; Qadri, Syed S Y H; Gupta, Krishna P

    2016-02-01

    Skin cancer is among the most common cancers worldwide and identifiable molecular changes for early and late stage of skin tumorigenesis can suggest the better targets for its control. In this study, we investigated the status of K-Ras-PI3K-AKTpathway followed by NF-κB, cyclin D1, MMP-9 and regulatory micro RNA during 7, 12-dimethylbenz[a]anthracene (DMBA) induced mouse skin tumorigenesis and its prevention by butyric acid (BA), nicotinamide (NA) and calcium glucarate (CAG), individually or in combination with respect to time. DMBA upregulated the K-Ras, PI3K, Akt, NF-κB, cyclin D1 and MMP-9, but downregulated the PTEN in a time dependent manner. DMBA also reduced the levels of micoRNA let-7a but induced the levels of miR-21 and miR-20a as a function of time. BA, NA and CAG were found to prevent DMBA induced changes, but they were most effective when used together in a combination. Reduced let-7a and miR-211 were correlated with the overexpression of K-Ras and MMP-9. Overexpression of miR-21 and miR-20a was correlated with the down regulation of PTEN and overexpression of Cyclin D1. Collectively, the enhanced chemopreventive potential of natural compound in combination via regulation of K-Ras-PI3K-AKTpathway along with regulatory micro RNAs provide a newer and effective mean for cancer management. PMID:26655363

  19. Caffeic Acid Inhibits UVB-induced Inflammation and Photocarcinogenesis Through Activation of Peroxisome Proliferator-activated Receptor-γ in Mouse Skin.

    Science.gov (United States)

    Balupillai, Agilan; Prasad, Rajendra N; Ramasamy, Karthikeyan; Muthusamy, Ganesan; Shanmugham, Mohana; Govindasamy, Kanimozhi; Gunaseelan, Srithar

    2015-11-01

    In this study, the effect of caffeic acid (CA) on both acute and chronic UVB-irradiation-induced inflammation and photocarcinogenesis was investigated in Swiss albino mice. Animals were exposed to 180 mJ cm(-2) of UVB once daily for 10 consecutive days and thrice weekly for 30 weeks for acute and chronic study respectively. UVB exposure for 10 consecutive days showed edema formation, increased lipid peroxidation and decreased antioxidant status with activation of inflammatory molecules such as TNF-α, IL-6, COX-2 and NF-κB. However, CA (15 mg per kg.b.wt.) administration before each UVB exposure decreased lipid peroxidation, inflammatory markers expression and enhanced antioxidant status probably through the activation of peroxisome proliferator-activated receptors (PPARγ) in the mice skin. PPARγ is considered a potential target for photochemoprevention because it inhibits UVB-mediated inflammatory responses. In this study, UVB exposure for 30 weeks caused squamous cell carcinoma and upregulation of iNOS, VEGF and TGF-β and downregulation of p53 and tumor incidence in the mice skin. Both topical (CAT) and intraperitoneal (CAIP) treatment before each UVB exposure downregulates iNOS, VEGF, TGF-β, upregulates p53 and reduces tumors multiplicity in the mice skin. Thus, CA offers protection against UVB-induced photocarcinogenesis probably through activation of anti-inflammatory transcription factor PPARγ in the mice.

  20. Aging Skin

    Science.gov (United States)

    ... email address Submit Home > Healthy Aging > Wellness Healthy Aging Aging skin More information on aging skin When it ... treated early. Return to top More information on Aging skin Read more from womenshealth.gov Varicose Veins ...

  1. Skin Conditions

    Science.gov (United States)

    Your skin is your body's largest organ. It covers and protects your body. Your skin Holds body fluids in, preventing dehydration Keeps harmful ... it Anything that irritates, clogs, or inflames your skin can cause symptoms such as redness, swelling, burning, ...

  2. 祛斑汤对小鼠皮肤黑素合成影响的研究%Study on the Effect of Qu-ban Decoction On the Melanin Synthesis in Mouse Skin

    Institute of Scientific and Technical Information of China (English)

    李艳; 艾儒棣; 肖桦; 郝平生

    2012-01-01

    To observe the effect of Qu-ban Decoction on melanin synthesis in the female C57BL/6J mouse skin and provide the experimental basis for exploring deeply the mechanism of treating melasma by the prescription. Methods; Female C57BL/ 6J mice were randomly divided into the blank control group, the Qu-ban Decoction low dose group (10 g/kg) , the middle dose group (20 g/kg) , the high dose group (40 g/kg) and the vitamin C group. Take the skin from mice fed with drug for 30 days. Use immu-nohistochemical techniques to observe the melanin distribution and the result was analyzed using the one-way ANOVA statistically. Results : The melanocytes that contained the melanin granules were named positive cells. The average optical densities of positive cells of the high dose group and the middle dose group were lower than the blank control group. The difference between the high dose group, the middle dose group and the blank control group was significant statistically (P <0. 01) . Conclusion; The Qu-ban Decoction can inhibit the melanin synthesis and reduce the melanin distribution in female C57BI/6J mouse skin.%目的:观察祛斑汤对雌性C57BL/6J小鼠皮肤黑素合成的影响,为探索该方剂治疗黄褐斑机制提供实验依据.方法:将雌性C57BL/6J小鼠随机分成空白对照组、祛斑汤低(10 g/kg)、中(20 g/kg)、高剂量(40 g/kg)组、维生素C组.各组灌胃给药30 d后皮肤取材.采用免疫组化法观察小鼠皮肤黑素分布.结果:祛斑汤高、中剂量组黑素颗粒阳性反应的黑素细胞平均光密度低于空白对照组,差别有统计学意义(P<0.01).结论:祛斑汤能抑制雌性C57BI/6J小鼠皮肤中黑素合成、降低黑素分布.

  3. RE1 silencing transcription factor/neuron-restrictive silencing factor regulates expansion of adult mouse subventricular zone-derived neural stem/progenitor cells in vitro.

    Science.gov (United States)

    Soldati, Chiara; Caramanica, Pasquale; Burney, Matthew J; Toselli, Camilla; Bithell, Angela; Augusti-Tocco, Gabriella; Stanton, Lawrence W; Biagioni, Stefano; Buckley, Noel J; Cacci, Emanuele

    2015-08-01

    Adult neural stem cell (aNSC) activity is tuned by external stimuli through the recruitment of transcription factors. This study examines the RE1 silencing transcription factor (REST) in neural stem/progenitor cells isolated from the subventricular zone of adult mouse brain and provides the first extensive characterization of REST-mediated control of the cellular and molecular properties. This study shows that REST knockdown affects the capacity of progenitor cells to generate neurospheres, reduces cell proliferation, and triggers cell differentiation despite the presence of growth factors. Genome- and transcriptome-wide analyses show that REST binding sites are significantly enriched in genes associated with synaptic transmission and nervous system development and function. Seeking candidate regulators of aNSC function, this study identifies a member of the bone morphogenetic protein (BMP) family, BMP6, the mRNA and protein of which increased after REST knockdown. The results of this study extend previous findings, demonstrating a reciprocal control of REST expression by BMPs. Administration of exogenous BMP6 inhibits aNSC proliferation and induces the expression of the astrocytic marker glial fibrillary acidic protein, highlighting its antimitogenic and prodifferentiative effects. This study suggests that BMP6 produced in a REST-regulated manner together with other signals can contribute to regulation of NSC maintenance and fate. PMID:25691247

  4. Isoform-Specific Modulation of Inflammation Induced by Adenoviral Mediated Delivery of Platelet-Derived Growth Factors in the Adult Mouse Heart

    Science.gov (United States)

    Ylä-Herttuala, Seppo; Betsholtz, Christer; Andrae, Johanna

    2016-01-01

    Platelet-derived growth factors (PDGFs) are key regulators of mesenchymal cells in vertebrate development. To what extent PDGFs also exert beneficial homeostatic or reparative roles in adult organs, as opposed to adverse fibrogenic responses in pathology, are unclear. PDGF signaling plays critical roles during heart development, during which forced overexpression of PDGFs induces detrimental cardiac fibrosis; other studies have implicated PDGF signaling in post-infarct myocardial repair. Different PDGFs may exert different effects mediated through the two PDGF receptors (PDGFRα and PDGFRβ) in different cell types. Here, we assessed responses induced by five known PDGF isoforms in the adult mouse heart in the context of adenovirus vector-mediated inflammation. Our results show that different PDGFs have different, in some cases even opposing, effects. Strikingly, whereas the major PDGFRα agonists (PDGF-A and -C) decreased the amount of scar tissue and increased the numbers of PDGFRα-positive fibroblasts, PDGFRβ agonists either induced large scars with extensive inflammation (PDGF-B) or dampened the adenovirus-induced inflammation and produced a small and dense scar (PDGF-D). These results provide evidence for PDGF isoform-specific inflammation-modulating functions that may have therapeutic implications. They also illustrate a surprising complexity in the PDGF-mediated pathophysiological responses. PMID:27513343

  5. Methods in laboratory investigation. Autoradiographic demonstration of the specific binding and nuclear localization of 3H-dexamethasone in adult mouse lung.

    Science.gov (United States)

    Beer, D G; Cunha, G R; Malkinson, A M

    1983-12-01

    This report describes the first autoradiographic demonstration of specific nuclear localization of 3H-dexamethasone in different cell types of the lung. Adult mouse lung tissue was incubated in vitro for 90 minutes with 17 nM 3H-dexamethasone in the presence or absence of various nonradioactive steroids. After extensive washing to remove any nonspecifically bound ligand, the specimens were processed for autoradiography using the thaw-mount method. In the absence of competing steroids, silver grains were localized in the nuclei of alveolar type II cells, bronchiolar and arteriolar smooth muscle cells, fibroblasts, and endothelial cells of the pulmonary vasculature. No significant nuclear concentration of label was observed in the bronchiolar epithelium, however. The specificity of 3H-dexamethasone labeling was demonstrated by incubating 17 nM 3H-dexamethasone with a 600-fold excess of either unlabeled dexamethasone, estrogen, dihydrotestosterone, or progesterone. These autoradiographic binding and steroid competition studies were confirmed by quantifying with liquid scintillation counting the specific 3H-dexamethasone binding in nuclear and cytosolic fractions prepared from lung tissues that had undergone identical incubation and washing procedures as those for autoradiography. These results demonstrate that many cell types in adult lung are targets for glucocorticoids and may respond to physiologic concentrations of this hormone.

  6. Effects of maternal L-tryptophan depletion and corticosterone administration on neurobehavioral adjustments in mouse dams and their adolescent and adult daughters.

    Science.gov (United States)

    Zoratto, Francesca; Berry, Alessandra; Anzidei, Francesca; Fiore, Marco; Alleva, Enrico; Laviola, Giovanni; Macrì, Simone

    2011-08-01

    Major depressive disorder (MDD), a pathology characterized by mood and neurovegetative disturbances, depends on a multi-factorial contribution of individual predisposition (e.g., diminished serotonergic transmission) and environmental factors (e.g., neonatal abuse or neglect). Despite its female-biased prevalence, MDD basic research has mainly focused on male rodents. Most of present models of depression are also devalued due to the fact that they typically address only one of the aforementioned pathogenetic factors. In this paper we first describe the basic principles behind mouse model development and evaluation and then articulate that current models of depression are intrinsically devalued due to poor construct and/or external validity. We then report a first attempt to overcome this limitation through the design of a mouse model in which the genetic and the environmental components of early risk factors for depression are mimicked together. Environmental stress is mimicked through the supplementation of corticosterone in the maternal drinking water while biological predisposition is mimicked through maternal access to an L-tryptophan (the serotonin precursor) deficient diet during the first week of lactation. CD1 dams and their offspring exposed to the L-tryptophan deficient diet (T) and to corticosterone (80mg/l; C) were compared to animal facility reared (AFR) subjects. T and C mice served as intermediate reference groups. Adolescent TC offspring, compared to AFR mice, showed decreased time spent floating in the forced-swim test and increased time spent in the open sectors of an elevated 0-maze. Adult TC offspring showed reduced preference for novelty, decreased breakpoints in the progressive ratio operant procedure and major alterations in central BDNF levels and altered HPA regulation. The route of administration and the possibility to control the independent variables predisposing to depressive-like symptoms disclose novel avenues towards the development

  7. The Skin Cancer and Sun Knowledge (SCSK) Scale: Validity, Reliability, and Relationship to Sun-Related Behaviors among Young Western Adults

    Science.gov (United States)

    Day, Ashley K.; Wilson, Carlene; Roberts, Rachel M.; Hutchinson, Amanda D.

    2014-01-01

    Increasing public knowledge remains one of the key aims of skin cancer awareness campaigns, yet diagnosis rates continue to rise. It is essential we measure skin cancer knowledge adequately so as to determine the nature of its relationship to sun-related behaviors. This study investigated the psychometric properties of a new measure of skin cancer…

  8. 5-HT1A/1B receptors as targets for optimizing pigmentary responses in C57BL/6 mouse skin to stress.

    Directory of Open Access Journals (Sweden)

    Hua-Li Wu

    Full Text Available Stress has been reported to induce alterations of skin pigmentary response. Acute stress is associated with increased turnover of serotonin (5-hydroxytryptamine; 5-HT whereas chronic stress causes a decrease. 5-HT receptors have been detected in pigment cells, indicating their role in skin pigmentation. To ascertain the precise role of 5-HT in stress-induced pigmentary responses, C57BL/6 mice were subjected to chronic restraint stress and chronic unpredictable mild stress (CRS and CUMS, two models of chronic stress for 21 days, finally resulting in abnormal pigmentary responses. Subsequently, stressed mice were characterized by the absence of a black pigment in dorsal coat. The down-regulation of tyrosinase (TYR and tyrosinase-related proteins (TRP1 and TRP2 expression in stressed skin was accompanied by reduced levels of 5-HT and decreased expression of 5-HT receptor (5-HTR system. In both murine B16F10 melanoma cells and normal human melanocytes (NHMCs, 5-HT had a stimulatory effect on melanin production, dendricity and migration. When treated with 5-HT in cultured hair follicles (HFs, the increased expression of melanogenesis-related genes and the activation of 5-HT1A, 1B and 7 receptors also occurred. The serum obtained from stressed mice showed significantly decreased tyrosinase activity in NHMCs compared to that from nonstressed mice. The decrease in tyrosinase activity was further augmented in the presence of 5-HTR1A, 1B and 7 antagonists, WAY100635, SB216641 and SB269970. In vivo, stressed mice received 5-HT precursor 5-hydroxy-l-tryptophan (5-HTP, a member of the class of selective serotonin reuptake inhibitors (fluoxetine; FX and 5-HTR1A/1B agonists (8-OH-DPAT/CP94253, finally contributing to the normalization of pigmentary responses. Taken together, these data strongly suggest that the serotoninergic system plays an important role in the regulation of stress-induced depigmentation, which can be mediated by 5-HT1A/1B receptors. 5-HT

  9. Fast, potent pharmacological expansion of endogenous hes3+/sox2+ cells in the adult mouse and rat hippocampus.

    Directory of Open Access Journals (Sweden)

    Simone Pacioni

    Full Text Available The adult hippocampus is involved in learning and memory. As a consequence, it is a brain region of remarkable plasticity. This plasticity exhibits itself both as cellular changes and neurogenesis. For neurogenesis to occur, a population of local stem cells and progenitor cells is maintained in the adult brain and these are able to proliferate and differentiate into neurons which contribute to the hippocampal circuitry. There is much interest in understanding the role of immature cells in the hippocampus, in relation to learning and memory. Methods and mechanisms that increase the numbers of these cells will be valuable in this research field. We show here that single injections of soluble factors into the lateral ventricle of adult rats and mice induces the rapid (within one week increase in the number of putative stem cells/progenitor cells in the hippocampus. The established progenitor marker Sox2 together with the more recently established marker Hes3, were used to quantify the manipulation of the Sox2/Hes3 double-positive cell population. We report that in both adult rodent species, Sox2+/Hes3+ cell numbers can be increased within one week. The most prominent increase was observed in the hilus of the dentate gyrus. This study presents a fast, pharmacological method to manipulate the numbers of endogenous putative stem cells/progenitor cells. This method may be easily modified to alter the degree of activation (e.g. by the use of osmotic pumps for delivery, or by repeat injections through implanted cannulas, in order to be best adapted to different paradigms of research (neurodegenerative disease, neuroprotection, learning, memory, plasticity, etc.

  10. NTPDase2 and Purinergic Signaling Control Progenitor Cell Proliferation in Neurogenic Niches of the Adult Mouse Brain

    OpenAIRE

    Gampe, Kristine; Stefani, Jennifer; Hammer, Klaus; Brendel, Peter; Pötzsch, Alexandra; Enikolopov, Grigori; Enjyoji, Keiichi; Acker-Palmer, Amparo; Robson, Simon C.; Zimmermann, Herbert

    2015-01-01

    Nerve cells are continuously generated from stem cells in the adult mammalian subventricular zone (SVZ) and hippocampal dentate gyrus. We have previously noted that stem/progenitor cells in the SVZ and the subgranular layer (SGL) of the dentate gyrus express high levels of plasma membrane-bound nucleoside triphosphate diphosphohydrolase 2 (NTPDase2), an ectoenzyme that hydrolyzes extracellular nucleoside di- and triphosphates. We inferred that deletion of NTPDase2 would increase local extrace...

  11. Anti-wrinkle effects of Sargassum muticum ethyl acetate fraction on ultraviolet B-irradiated hairless mouse skin and mechanistic evaluation in the human HaCaT keratinocyte cell line.

    Science.gov (United States)

    Song, Jae Hyoung; Piao, Mei Jing; Han, Xia; Kang, Kyoung Ah; Kang, Hee Kyoung; Yoon, Weon Jong; Ko, Mi Hee; Lee, Nam Ho; Lee, Mi Young; Chae, Sungwook; Hyun, Jin Won

    2016-10-01

    The present study investigated the photoprotective properties of the ethyl acetate fraction of Sargassum muticum (SME) against ultraviolet B (UVB)‑induced skin damage and photoaging in a mouse model. HR‑1 strain hairless male mice were divided into three groups: An untreated control group, a UVB‑irradiated vehicle group and a UVB‑irradiated SME group. The UVB‑irradiated mice in the SME group were orally administered with SME (100 mg/kg body weight in 0.1 ml water per day) and then exposed to radiation at a dose of 60‑120 mJ/cm2. Wrinkle formation and skin damage were evaluated by analysis of skin replicas, epidermal thickness and collagen fiber integrity in the dermal connective tissue. The mechanism underlying the action of SME was also investigated in the human HaCaT keratinocyte cell line following exposure of the cells to UVB at a dose of 30 mJ/cm2. The protein expression levels and activity of matrix metalloproteinase‑1 (MMP‑1), and the binding of activator protein‑1 (AP‑1) to the MMP‑1 promoter were assessed in the HaCaT cells using western blot analysis, an MMP‑1 fluorescent assay and a chromatin immune‑precipitation assay, respectively. The results showed that the mean length and depth of the wrinkles in the UVB‑exposed hairless mice were significantly improved by oral administration of SME, which also prevented the increase in epidermal thickness triggered by UVB irradiation. Furthermore, a marked increase in collagen bundle formation was observed in the UVB‑treated mice with SME administration. SME pretreatment also significantly inhibited the UVB‑induced upregulation in the expression and activity of MMP‑1 in the cultured HaCaT keratinocytes, and the UVB‑enhanced association of AP‑1 with the MMP‑1 promoter. These results suggested that SME may be useful as an anti-photoaging resource for the skin. PMID:27573915

  12. Impaired adult hippocampal neurogenesis and its partial reversal by chronic treatment of fluoxetine in a mouse model of Angelman syndrome.

    Science.gov (United States)

    Godavarthi, Swetha K; Dey, Parthanarayan; Sharma, Ankit; Jana, Nihar Ranjan

    2015-09-01

    Angelman syndrome (AS) is a neurodevelopmental disorder characterized by severe cognitive and motor deficits, caused by the loss of function of maternally inherited Ube3a. Ube3a-maternal deficient mice (AS model mice) recapitulate many essential features of AS, but how the deficiency of Ube3a lead to such behavioural abnormalities is poorly understood. Here we have demonstrated significant impairment of adult hippocampal neurogenesis in AS mice brain. Although, the number of BrdU and Ki67-positive cell in the hippocampal DG region was nearly equal at early postnatal days among wild type and AS mice, they were significantly reduced in adult AS mice compared to wild type controls. Reduced number of doublecortin-positive immature neurons in this region of AS mice further indicated impaired neurogenesis. Unaltered BrdU and Ki67-positive cells number in the sub ventricular zone of adult AS mice brain along with the absence of imprinted expression of Ube3a in the neural progenitor cell suggesting that Ube3a may not be directly linked with altered neurogenesis. Finally, we show that the impaired hippocampal neurogenesis in these mice can be partially rescued by the chronic treatment of antidepressant fluoxetine. These results suggest that the chronic stress may lead to reduced hippocampal neurogenesis in AS mice and that impaired neurogenesis could contribute to cognitive disturbances observed in these mice. PMID:26231800

  13. Skin Biomes.

    Science.gov (United States)

    Fyhrquist, N; Salava, A; Auvinen, P; Lauerma, A

    2016-05-01

    The cutaneous microbiome has been investigated broadly in recent years and some traditional perspectives are beginning to change. A diverse microbiome exists on human skin and has a potential to influence pathogenic microbes and modulate the course of skin disorders, e.g. atopic dermatitis. In addition to the known dysfunctions in barrier function of the skin and immunologic disturbances, evidence is rising that frequent skin disorders, e.g. atopic dermatitis, might be connected to a dysbiosis of the microbial community and changes in the skin microbiome. As a future perspective, examining the skin microbiome could be seen as a potential new diagnostic and therapeutic target in inflammatory skin disorders.

  14. Lead induces similar gene expression changes in brains of gestationally exposed adult mice and in neurons differentiated from mouse embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Francisco Javier Sánchez-Martín

    Full Text Available Exposure to environmental toxicants during embryonic life causes changes in the expression of developmental genes that may last for a lifetime and adversely affect the exposed individual. Developmental exposure to lead (Pb, an ubiquitous environmental contaminant, causes deficits in cognitive functions and IQ, behavioral effects, and attention deficit hyperactivity disorder (ADHD. Long-term effects observed after early life exposure to Pb include reduction of gray matter, alteration of myelin structure, and increment of criminal behavior in adults. Despite growing research interest, the molecular mechanisms responsible for the effects of lead in the central nervous system are still largely unknown. To study the molecular changes due to Pb exposure during neurodevelopment, we exposed mice to Pb in utero and examined the expression of neural markers, neurotrophins, transcription factors and glutamate-related genes in hippocampus, cortex, and thalamus at postnatal day 60. We found that hippocampus was the area where gene expression changes due to Pb exposure were more pronounced. To recapitulate gestational Pb exposure in vitro, we differentiated mouse embryonic stem cells (ESC into neurons and treated ESC-derived neurons with Pb for the length of the differentiation process. These neurons expressed the characteristic neuronal markers Tubb3, Syp, Gap43, Hud, Ngn1, Vglut1 (a marker of glutamatergic neurons, and all the glutamate receptor subunits, but not the glial marker Gafp. Importantly, several of the changes observed in Pb-exposed mouse brains in vivo were also observed in Pb-treated ESC-derived neurons, including those affecting expression of Ngn1, Bdnf exon IV, Grin1, Grin2D, Grik5, Gria4, and Grm6. We conclude that our ESC-derived model of toxicant exposure during neural differentiation promises to be a useful model to analyze mechanisms of neurotoxicity induced by Pb and other environmental agents.

  15. A comparison of the multiple oocyte maturation gene expression patterns between the newborn and adult mouse ovary

    OpenAIRE

    Soghra Bahmanpour; Tahereh Talaei Khozani; Nehleh Zarei fard; Mansoureh Jaberipour; Ahmah Hosseini; Tahereh Esmaeilpour

    2013-01-01

    Background: The interaction between follicular cells and oocyte leads to a change in gene expression involved in oocyte maturation processes. Objective: The purpose of this study was to quantify the expression of more common genes involved in follicular growth and oocyte developmental competence. Materials and Methods: In this experimental study, the expression of genes was evaluated with qRT-PCR assay in female BALB/c mice pups at 3-day of pre-pubertal and 8 week old virgin adult ovaries. Th...

  16. A chemokine targets the nucleus: Cxcl12-gamma isoform localizes to the nucleolus in adult mouse heart.

    Directory of Open Access Journals (Sweden)

    Raul Torres

    Full Text Available Chemokines are extracellular mediators of complex regulatory circuits involved principally in cell-to-cell communication. Most studies to date of the essential chemokine Cxcl12 (Sdf-1 have focused on the ubiquitously expressed secreted isoforms alpha and beta. Here we show that, unlike these isoforms and all other known chemokines, the alternatively transcribed gamma isoform is an intracellular protein that localizes to the nucleolus in differentiated mouse Cardiac tissue. Our results demonstrate that nucleolar transportation is encoded by a nucleolar-localization signal in the unique carboxy-terminal region of Sdf-1gamma, and is competent both in vivo and in vitro. The molecular mechanism underlying these unusual chemokine properties involves cardiac-specific transcription of an mRNA containing a unique short-leader sequence lacking the signal peptide and translation from a non-canonical CUG codon. Our results provide an example of genome economy even for essential and highly conserved genes such as Cxcl12, and suggest that chemokines can exert tissue specific functions unrelated to cell-to-cell communication.

  17. The effects of cellular phone waves on the frequency micronucleus in newborn and adult Balb/C mouse

    Directory of Open Access Journals (Sweden)

    Javad Baharara

    2011-09-01

    Full Text Available Background: In recent years, the widespread use of microwave producing instruments specially cell phones; result in growing concern regarding the possible effects associated with these waves on human health especially pregnant woman and neonates. In present study, we investigated the genotoxic effects of cell phone radiation on the mice (Balb/C and their offspring. Materials and Method: In this experimental research, pregnant mice were irradiated with cell phone for 4 days of gestational age (days 14th-18th, 6h per day, from 9am until 3pm and after litter, 2nd-day offspring studied for morphology, weight and CR length. By following, for assessment of possible genetic damages in erythrocytes after bleeding from heart, smears of spleen tissue prepeard for histological studies. Mice peripheral blood and bone marrow smears prepared and stained with May-Granowald and Gimsa.Results: The finding in experimental group indicated that cell phone radiation decreased offsprings’ weight and CR length (p0.05. An increase in micronucleus frequency in peripheral blood erythrocytes were seen in experimental newborn (p=0.006 and adult mice (p0.05.Conclusion: Above findings indicated that cell phone radiation (940 MHZ are able to increase the frequency of micronucleus in peripheral blood erythrocytes of adult mice and their of fsprings and induce a genotoxic response

  18. Impaired skin regeneration and remodeling after cutaneous injury and chemically induced hyperplasia in taps-transgenic mice.

    Science.gov (United States)

    Hildenbrand, Maike; Rhiemeier, Verena; Hartenstein, Bettina; Lahrmann, Bernd; Grabe, Niels; Angel, Peter; Hess, Jochen

    2010-07-01

    Recently, we identified an AP-1-dependent target gene in 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated mouse back skin, which encodes a retroviral-like aspartic proteinase (Taps/Asprv1). Taps expression was detected almost exclusively in stratified epithelia of mouse embryos and adult tissues, and enhanced protein levels were present in several non-neoplastic human skin disorders, implicating a crucial role for differentiation and homeostasis of multilayered epithelia. Here, we generated a mouse model in which Taps transgene expression is under the control of the human ubiquitin C promoter (UBC-Taps). Although no obvious phenotype was observed in normal skin development and homeostasis, these mice showed a significant delay in cutaneous wound closure compared with control animals. Shortly after re-epithelialization, we found an increase in keratinocytes in the stratum granulosum, which express Filaggrin, a late differentiation marker. A hypergranulosum-like phenotype with increased numbers of Filaggrin-positive keratinocytes was also observed in UBC-Taps mice after administration of TPA. In summary, these data show that aberrant Taps expression causes impaired skin regeneration and skin remodeling after cutaneous injury and chemically induced hyperplasia. PMID:20237492

  19. Modulation of miR-203 and its regulators as a function of time during the development of 7, 12 dimethylbenz [a] anthracene induced mouse skin tumors in presence or absence of the antitumor agents

    International Nuclear Information System (INIS)

    We investigated the chemopreventive effects of naturally occurring compounds like butyric acid (BA), nicotinamide (NA) and calcium glucarate (CAG) individually or in combination in 7, 12-dimethylbenz [a] anthracene (DMBA) treated mouse skin at 4 and 16 weeks, the time before and after the tumor development. DMBA application did not show any skin tumors at 4 weeks but well defined tumors appeared at 16 weeks. BA, NA or CAG prevented the tumor development significantly but the protection was highly enhanced when all these compounds were given together. In order to see the molecular changes progressing with tumors, we showed the downregulation of tumor suppressor miR-203 at 16 weeks and upregulation of histone deacetylases (HDAC), DNA methyltransferase, promoter methylation of miR-203 at 4 or 16 weeks. Regulators of micro RNA biogenesis such as DICER1 and Ago2 were also deregulated by DMBA. Proto-oncogene c-myc and BMI1 were upregulated and tumor suppressor gene p16 was downregulated by DMBA as a function of time. Effects of BA, NA or CAG were more pronounced after 16 weeks as compared to 4 weeks in preventing the tumor development and altered gene expression. Concomitant administration of BA, NA and CAG tried to prevent these alterations more effectively than that of individual compound possibly by regulating miR-203 status through epigenetic or biogenetic modulations before and after the tumor development. Study provides a rationale for chemoprevention by combination of different compounds targeting miR-203. - Highlights: • DMBA modulates miR-203 and its regulator before and after the onset of tumors. • Suppression of miR-203 and p16 could be the result of gene promoter methylation. • BA, NA or CAG prevents the effects of DMBA. • Combination of BA, NA or CAG is more effective in preventing the DMBA modulations

  20. Modulation of miR-203 and its regulators as a function of time during the development of 7, 12 dimethylbenz [a] anthracene induced mouse skin tumors in presence or absence of the antitumor agents

    Energy Technology Data Exchange (ETDEWEB)

    Tiwari, Prakash; Gupta, Krishna P., E-mail: krishnag522@yahoo.co.in

    2014-07-15

    We investigated the chemopreventive effects of naturally occurring compounds like butyric acid (BA), nicotinamide (NA) and calcium glucarate (CAG) individually or in combination in 7, 12-dimethylbenz [a] anthracene (DMBA) treated mouse skin at 4 and 16 weeks, the time before and after the tumor development. DMBA application did not show any skin tumors at 4 weeks but well defined tumors appeared at 16 weeks. BA, NA or CAG prevented the tumor development significantly but the protection was highly enhanced when all these compounds were given together. In order to see the molecular changes progressing with tumors, we showed the downregulation of tumor suppressor miR-203 at 16 weeks and upregulation of histone deacetylases (HDAC), DNA methyltransferase, promoter methylation of miR-203 at 4 or 16 weeks. Regulators of micro RNA biogenesis such as DICER1 and Ago2 were also deregulated by DMBA. Proto-oncogene c-myc and BMI1 were upregulated and tumor suppressor gene p16 was downregulated by DMBA as a function of time. Effects of BA, NA or CAG were more pronounced after 16 weeks as compared to 4 weeks in preventing the tumor development and altered gene expression. Concomitant administration of BA, NA and CAG tried to prevent these alterations more effectively than that of individual compound possibly by regulating miR-203 status through epigenetic or biogenetic modulations before and after the tumor development. Study provides a rationale for chemoprevention by combination of different compounds targeting miR-203. - Highlights: • DMBA modulates miR-203 and its regulator before and after the onset of tumors. • Suppression of miR-203 and p16 could be the result of gene promoter methylation. • BA, NA or CAG prevents the effects of DMBA. • Combination of BA, NA or CAG is more effective in preventing the DMBA modulations.

  1. Identification and Characterization of Lineage(-)CD45(-)Sca-1(+) VSEL Phenotypic Cells Residing in Adult Mouse Bone Tissue.

    Science.gov (United States)

    Nakatsuka, Ryusuke; Iwaki, Ryuji; Matsuoka, Yoshikazu; Sumide, Keisuke; Kawamura, Hiroshi; Fujioka, Tatsuya; Sasaki, Yutaka; Uemura, Yasushi; Asano, Hiroaki; Kwon, A-Hon; Sonoda, Yoshiaki

    2016-01-01

    Murine bone marrow (BM)-derived very small embryonic-like stem cells (BM VSELs), defined by a lineage-negative (Lin(-)), CD45-negative (CD45(-)), Sca-1-positive (Sca-1(+)) immunophenotype, were previously reported as postnatal pluripotent stem cells (SCs). We developed a highly efficient method for isolating Lin(-)CD45(-)Sca-1(+) small cells using enzymatic treatment of murine bone. We designated these cells as bone-derived VSELs (BD VSELs). The incidences of BM VSELs in the BM-derived nucleated cells and that of BD VSELs in bone-derived nucleated cells were 0.002% and 0.15%, respectively. These BD VSELs expressed a variety of hematopoietic stem cell (HSC), mesenchymal stem cell (MSC), and endothelial cell markers. The gene expression profile of the BD VSELs was clearly distinct from those of HSCs, MSCs, and ES cells. In the steady state, the BD VSELs proliferated slowly, however, the number of BD VSELs significantly increased in the bone after acute liver injury. Moreover, green fluorescent protein-mouse derived BD VSELs transplanted via tail vein injection after acute liver injury were detected in the liver parenchyma of recipient mice. Immunohistological analyses suggested that these BD VSELs might transdifferentiate into hepatocytes. This study demonstrated that the majority of the Lin(-)CD45(-)Sca-1(+) VSEL phenotypic cells reside in the bone rather than the BM. However, the immunophenotype and the gene expression profile of BD VSELs were clearly different from those of other types of SCs, including BM VSELs, MSCs, HSCs, and ES cells. Further studies will therefore be required to elucidate their cellular and/or SC characteristics and the potential relationship between BD VSELs and BM VSELs.

  2. Childhood Physical and Sexual Abuse in Caribbean Young Adults and Its Association with Depression, Post-Traumatic Stress, and Skin Bleaching

    OpenAIRE

    James, Caryl; Seixas, Azizi A; Harrison, Abigail; Jean-Louis, Girardin; Butler, Mark; Zizi, Ferdinand; Samuels, Alafia

    2015-01-01

    Background The global prevalence of skin depigmentation/skin bleaching among blacks, estimated at 35%, is on the rise and is associated with a host of negative health and medical consequences. Current etiological approaches do not fully capture the emotional and psychological underpinnings of skin bleaching. The current study investigated the potential mediating role of depression, or post-traumatic stress symptoms (avoidance and hyperarousal) on the relationship between childhood physical an...

  3. Effects of Chronic Sleep Restriction during Early Adolescence on the Adult Pattern of Connectivity of Mouse Secondary Motor Cortex123

    Science.gov (United States)

    Billeh, Yazan N.; Bernard, Amy; de Vivo, Luisa; Honjoh, Sakiko; Mihalas, Stefan; Ng, Lydia; Koch, Christof

    2016-01-01

    Abstract Cortical circuits mature in stages, from early synaptogenesis and synaptic pruning to late synaptic refinement, resulting in the adult anatomical connection matrix. Because the mature matrix is largely fixed, genetic or environmental factors interfering with its establishment can have irreversible effects. Sleep disruption is rarely considered among those factors, and previous studies have focused on very young animals and the acute effects of sleep deprivation on neuronal morphology and cortical plasticity. Adolescence is a sensitive time for brain remodeling, yet whether chronic sleep restriction (CSR) during adolescence has long-term effects on brain connectivity remains unclear. We used viral-mediated axonal labeling and serial two-photon tomography to measure brain-wide projections from secondary motor cortex (MOs), a high-order area with diffuse projections. For each MOs target, we calculated the projection fraction, a combined measure of passing fibers and axonal terminals normalized for the size of each target. We found no homogeneous differences in MOs projection fraction between mice subjected to 5 days of CSR during early adolescence (P25–P30, ≥50% decrease in daily sleep, n=14) and siblings that slept undisturbed (n=14). Machine learning algorithms, however, classified animals at significantly above chance levels, indicating that differences between the two groups exist, but are subtle and heterogeneous. Thus, sleep disruption in early adolescence may affect adult brain connectivity. However, because our method relies on a global measure of projection density and was not previously used to measure connectivity changes due to behavioral manipulations, definitive conclusions on the long-term structural effects of early CSR require additional experiments. PMID:27351022

  4. Effects of Chronic Sleep Restriction during Early Adolescence on the Adult Pattern of Connectivity of Mouse Secondary Motor Cortex.

    Science.gov (United States)

    Billeh, Yazan N; Rodriguez, Alexander V; Bellesi, Michele; Bernard, Amy; de Vivo, Luisa; Funk, Chadd M; Harris, Julie; Honjoh, Sakiko; Mihalas, Stefan; Ng, Lydia; Koch, Christof; Cirelli, Chiara; Tononi, Giulio

    2016-01-01

    Cortical circuits mature in stages, from early synaptogenesis and synaptic pruning to late synaptic refinement, resulting in the adult anatomical connection matrix. Because the mature matrix is largely fixed, genetic or environmental factors interfering with its establishment can have irreversible effects. Sleep disruption is rarely considered among those factors, and previous studies have focused on very young animals and the acute effects of sleep deprivation on neuronal morphology and cortical plasticity. Adolescence is a sensitive time for brain remodeling, yet whether chronic sleep restriction (CSR) during adolescence has long-term effects on brain connectivity remains unclear. We used viral-mediated axonal labeling and serial two-photon tomography to measure brain-wide projections from secondary motor cortex (MOs), a high-order area with diffuse projections. For each MOs target, we calculated the projection fraction, a combined measure of passing fibers and axonal terminals normalized for the size of each target. We found no homogeneous differences in MOs projection fraction between mice subjected to 5 days of CSR during early adolescence (P25-P30, ≥ 50% decrease in daily sleep, n=14) and siblings that slept undisturbed (n=14). Machine learning algorithms, however, classified animals at significantly above chance levels, indicating that differences between the two groups exist, but are subtle and heterogeneous. Thus, sleep disruption in early adolescence may affect adult brain connectivity. However, because our method relies on a global measure of projection density and was not previously used to measure connectivity changes due to behavioral manipulations, definitive conclusions on the long-term structural effects of early CSR require additional experiments. PMID:27351022

  5. Mouse Prkar1a haploinsufficiency leads to an increase in tumors in the Trp53+/− or Rb1+/− backgrounds and chemically induced skin papillomas by dysregulation of the cell cycle and Wnt signaling

    Science.gov (United States)

    Almeida, Madson Q.; Muchow, Michael; Boikos, Sosipatros; Bauer, Andrew J.; Griffin, Kurt J.; Tsang, Kit Man; Cheadle, Chris; Watkins, Tonya; Wen, Feng; Starost, Matthew F.; Bossis, Ioannis; Nesterova, Maria; Stratakis, Constantine A.

    2010-01-01

    PRKAR1A inactivation leads to dysregulated cAMP signaling and Carney complex (CNC) in humans, a syndrome associated with skin, endocrine and other tumors. The CNC phenotype is not easily explained by the ubiquitous cAMP signaling defect; furthermore, Prkar1a+/− mice did not develop skin and other CNC tumors. To identify whether a Prkar1a defect is truly a generic but weak tumorigenic signal that depends on tissue-specific or other factors, we investigated Prkar1a+/− mice when bred within the Rb1+/− or Trp53+/− backgrounds, or treated with a two-step skin carcinogenesis protocol. Prkar1a+/− Trp53+/− mice developed more sarcomas than Trp53+/− mice (P < 0.05) and Prkar1a+/− Rb1+/− mice grew more (and larger) pituitary and thyroid tumors than Rb1+/− mice. All mice with double heterozygosity had significantly reduced life-spans compared with their single-heterozygous counterparts. Prkar1a+/− mice also developed more papillomas than wild-type animals. A whole-genome transcriptome profiling of tumors produced by all three models identified Wnt signaling as the main pathway activated by abnormal cAMP signaling, along with cell cycle abnormalities; all changes were confirmed by qRT–PCR array and immunohistochemistry. siRNA down-regulation of Ctnnb1, E2f1 or Cdk4 inhibited proliferation of human adrenal cells bearing a PRKAR1A-inactivating mutation and Prkar1a+/− mouse embryonic fibroblasts and arrested both cell lines at the G0/G1 phase of the cell cycle. In conclusion, Prkar1a haploinsufficiency is a relatively weak tumorigenic signal that can act synergistically with other tumor suppressor gene defects or chemicals to induce tumors, mostly through Wnt-signaling activation and cell cycle dysregulation, consistent with studies in human neoplasms carrying PRKAR1A defects. PMID:20080939

  6. Trypanosoma cruzi: in vivo evaluation of iron in skin employing X-ray fluorescence (XRF) in mouse strains that differ in their susceptibility to infection.

    Science.gov (United States)

    Estevam, Marcelo; Appoloni, Carlos Roberto; Malvezi, Aparecida Donizette; Tatakihara, Vera Lúcia Hideko; Panis, Carolina; Cecchini, Rubens; Rizzo, Luiz Vicente; Pinge-Filho, Phileno

    2012-04-01

    Trypanosoma cruzi, the causative agent of Chagas' disease (CD), is a substantial public health concern in Latin America. Laboratory mice inoculated with T. cruzi have served as important animal models of acute CD. Host hypoferremic responses occur during T. cruzi infection; therefore, it has been hypothesized that T. cruzi requires iron for optimal growth in host cells and, unlike extracellular pathogens, may benefit from host hypoferremic responses. Recent technological improvements of X-ray fluorescence are useful for diagnostics or monitoring in biomedical applications. The goal of our study was to determine whether the iron availabilities in Swiss and C57BL/6 mice differ during the acute phase of T. cruzi infection and whether the availability correlates with oxidative stress in the susceptible and resistant phenotypes identified in these mice. Our results showed that the decrease in iron levels in the skin of resistant infected mice correlated with the increase in oxidative stress associated with anemia and the reduction in parasite burden. PMID:22136203

  7. Keloid-derived, plasma/fibrin-based skin equivalents generate de novo dermal and epidermal pathology of keloid fibrosis in a mouse model.

    Science.gov (United States)

    Lee, Yun-Shain; Hsu, Tim; Chiu, Wei-Chih; Sarkozy, Heidi; Kulber, David A; Choi, Aaron; Kim, Elliot W; Benya, Paul D; Tuan, Tai-Lan

    2016-03-01

    Keloids are wounding-induced tumor-like human scars. Unclear etiology and lack of animal models to reveal disease mechanisms and invent therapies deepen the grievous health and psychosocial state of vulnerable individuals. Epitomizing the injury-repair environment which triggers and fosters keloid formation and essential dermal/epidermal interactions in disease development, the novel animal model was established by implanting porous polyethylene ring-supported plasma/fibrin-based epidermal-dermal skin constructs on the dorsum of athymic NU/J mice. The implants were stable to 18 weeks, contained abundant human cells, and remodeled to yield scar architecture characteristic of keloid fibrosis compared with normal implants and clinical specimens: (1) macroscopic convex or nodular scar morphology; (2) morphogenesis and accumulation of large collagen bundles from collagen-null initial constructs; (3) epidermal hyperplasia, aberrant epidermal-dermal patency, and features of EMT; (4) increased vasculature, macrophage influx, and aggregation; and (5) temporal-spatial increased collagen-inducing PAI-1 and its interactive partner uPAR expression. Development of such pathology in the NU/J host suggests that T-cell participation is less important at this stage than at keloid initiation. These accessible implants also healed secondary excisional wounds, enabling clinically relevant contemporaneous wounding and treatment strategies, and evaluation. The model provides a robust platform for studying keloid formation and testing knowledge-based therapies. PMID:26683740

  8. Single cell electroporation for longitudinal imaging of synaptic structure and function in the adult mouse neocortex in vivo

    Directory of Open Access Journals (Sweden)

    Stephane ePages

    2015-04-01

    Full Text Available Longitudinal imaging studies of neuronal structures in vivo have revealed rich dynamics in dendritic spines and axonal boutons. Spines and boutons are considered to be proxies for synapses. This implies that synapses display similar dynamics. However, spines and boutons do not always bear synapses, some may contain more than one, and dendritic shaft synapses have no clear structural proxies. In addition, synaptic strength is not always accurately revealed by just the size of these structures. Structural and functional dynamics of synapses could be studied more reliably using fluorescent synaptic proteins as markers for size and function. These proteins are often large and possibly interfere with circuit development, which renders them less suitable for conventional transfection or transgenesis methods such as viral vectors, in utero electroporation and germline transgenesis. Single cell electroporation has been shown to be a potential alternative for transfection of recombinant fluorescent proteins in adult cortical neurons. Here we provide proof of principle for the use of single cell electroporation to express and subsequently image fluorescently tagged synaptic proteins over days to weeks in vivo.

  9. Dividing and newly produced cells in the corpus callosum of adult mouse cerebrum as detected by light microscopic radioautography

    Energy Technology Data Exchange (ETDEWEB)

    Paterson, J.A. (Winnipeg Univ., Manitoba (Canada). Dept. of Anatomy)

    1983-01-01

    New cell production in the corpus callosum and subependyma of 4 month old mice was analyzed by light microscopic autoradiography after /sup 3/H-thymidine injections. In the subependymal region of the lateral ventricle, about 10% of cells were labelled in mice examined 2 h after /sup 3/H-thymidine, and 40 to 50% of cells were labelled after 7 d of isotope infusion. In corpus callosum of mice 2 h after precursor injection, the few cells (0.1 to 0.2 %) that were labelled had the appearance of 'immature cells', and were presumably incompletely differentiated neuroglial precursor cells which were preparing to divide. After 7 d of continuous /sup 3/H-thymidine administration, more labelled neuroglia (about 2%) were detected in corpus callosum; these newly produced cells included several astrocytes and some oligodendrocytes, as well as immature cells. Since the immature cells were the most frequently observed type of dividing cell within the normal adult corpus callosum, it is probable that the new astrocytes and oligodendrocytes were the products of divisions of their respective precursor cells.

  10. Sagging Skin

    Science.gov (United States)

    ... turkey neck,” this occurs as skin loses its elasticity and in cases where individuals have lost a ... technique or procedure is appropriate for my skin type? Did the doctor show me before-and-after ...

  11. Skin Dictionary

    Science.gov (United States)

    ... resources Meet our partners Español Donate Diseases and treatments Acne and rosacea Bumps and growths Color problems Contagious skin diseases Cosmetic treatments Dry / sweaty skin Eczema / dermatitis Hair and scalp ...

  12. Skin Biopsy

    Science.gov (United States)

    ... skin condition cannot be diagnosed by the patient's history and what the physician finds on examination alone. Confirming a clinical diagnosis may also be necessary prior to starting therapy. Skin biopsy types are as follows: Shave biopsies Punch biopsies ...

  13. Skin tears.

    Science.gov (United States)

    Baranoski, S

    2001-08-01

    Skin tears are a serious, painful problem for older patients. Find out how your staff can recognize patients at risk, what they can do to prevent skin tears, and how to manage them effectively if they occur.

  14. Skin Cancer

    Science.gov (United States)

    Skin cancer is the most common form of cancer in the United States. The two most common types ... face, neck, hands, and arms. Another type of skin cancer, melanoma, is more dangerous but less common. Anyone ...

  15. Periostin in Skin Tissue Skin-Related Diseases

    Directory of Open Access Journals (Sweden)

    Yukie Yamaguchi

    2014-01-01

    Recently, periostin—a matricellular protein—has been highlighted for its pivotal functions in the skin. Analysis of periostin null mice has revealed that periostin contributes to collagen fibrillogenesis, collagen cross-linking, and the formation of ECM meshwork via interactions with other ECM components. Periostin expression is enhanced by mechanical stress or skin injury; this is indicative of the physiologically protective functions of periostin, which promotes wound repair by acting on keratinocytes and fibroblasts. Along with its physiological functions, periostin plays pathogenic roles in skin fibrosis and chronic allergic inflammation. In systemic sclerosis (SSc patients, periostin levels reflect the severity of skin fibrosis. Periostin null mice have shown reduced skin fibrosis in a bleomycin-induced SSc mouse model, indicating a key role of periostin in fibrosis. Moreover, in atopic dermatitis (AD, attenuated AD phenotype has been observed in periostin null mice in a house dust mite extract-induced AD mouse model. Th2 cytokine-induced periostin acts on keratinocytes to produce inflammatory cytokines that further enhance the Th2 response, thereby sustaining and amplifying chronic allergic inflammation. Thus, periostin is deeply involved in the pathogenesis of AD and other inflammation-related disorders affecting the skin. Understanding the dynamic actions of periostin would be key to dissecting pathogenesis of skin-related diseases and to developing novel therapeutic strategies.

  16. SKIN CANCER

    OpenAIRE

    Made Putri Hendaria; AAGN Asmarajaya; Sri Maliawan

    2013-01-01

    Skin is an organ which protect the human body from the environment. It was build by milion cells. According to the changes in human lifestyle which tends to unhealthy life, increasing ultraviolet radiation, toxins, and genetics makes the cells who build the skin do the abnormal growth being cancer cells. Classification of skin cancer is according the most common three types, they are Basal Cell Carcinoma, Squamous Cell Carcinoma, and Malignant Melanoma. More than 3,5 milion skin cancer cases ...

  17. Skin Aging

    Science.gov (United States)

    Your skin changes as you age. You might notice wrinkles, age spots and dryness. Your skin also becomes thinner and loses fat, making it ... heal, too. Sunlight is a major cause of skin aging. You can protect yourself by staying out ...

  18. A Western diet ecological module identified from the 'humanized' mouse microbiota predicts diet in adults and formula feeding in children.

    Directory of Open Access Journals (Sweden)

    Jay Siddharth

    Full Text Available The interplay between diet and the microbiota has been implicated in the growing frequency of chronic diseases associated with the Western lifestyle. However, the complexity and variability of microbial ecology in humans and preclinical models has hampered identification of the molecular mechanisms underlying the association of the microbiota in this context. We sought to address two key questions. Can the microbial ecology of preclinical models predict human populations? And can we identify underlying principles that surpass the plasticity of microbial ecology in humans? To do this, we focused our study on diet; perhaps the most influential factor determining the composition of the gut microbiota. Beginning with a study in 'humanized' mice we identified an interactive module of 9 genera allied with Western diet intake. This module was applied to a controlled dietary study in humans. The abundance of the Western ecological module correctly predicted the dietary intake of 19/21 top and 21/21 of the bottom quartile samples inclusive of all 5 Western and 'low-fat' diet subjects, respectively. In 98 volunteers the abundance of the Western module correlated appropriately with dietary intake of saturated fatty acids, fat-soluble vitamins and fiber. Furthermore, it correlated with the geographical location and dietary habits of healthy adults from the Western, developing and third world. The module was also coupled to dietary intake in children (and piglets correlating with formula (vs breast feeding and associated with a precipitous development of the ecological module in young children. Our study provides a conceptual platform to translate microbial ecology from preclinical models to humans and identifies an ecological network module underlying the association of the gut microbiota with Western dietary habits.

  19. A Western diet ecological module identified from the 'humanized' mouse microbiota predicts diet in adults and formula feeding in children.

    Science.gov (United States)

    Siddharth, Jay; Holway, Nicholas; Parkinson, Scott J

    2013-01-01

    The interplay between diet and the microbiota has been implicated in the growing frequency of chronic diseases associated with the Western lifestyle. However, the complexity and variability of microbial ecology in humans and preclinical models has hampered identification of the molecular mechanisms underlying the association of the microbiota in this context. We sought to address two key questions. Can the microbial ecology of preclinical models predict human populations? And can we identify underlying principles that surpass the plasticity of microbial ecology in humans? To do this, we focused our study on diet; perhaps the most influential factor determining the composition of the gut microbiota. Beginning with a study in 'humanized' mice we identified an interactive module of 9 genera allied with Western diet intake. This module was applied to a controlled dietary study in humans. The abundance of the Western ecological module correctly predicted the dietary intake of 19/21 top and 21/21 of the bottom quartile samples inclusive of all 5 Western and 'low-fat' diet subjects, respectively. In 98 volunteers the abundance of the Western module correlated appropriately with dietary intake of saturated fatty acids, fat-soluble vitamins and fiber. Furthermore, it correlated with the geographical location and dietary habits of healthy adults from the Western, developing and third world. The module was also coupled to dietary intake in children (and piglets) correlating with formula (vs breast) feeding and associated with a precipitous development of the ecological module in young children. Our study provides a conceptual platform to translate microbial ecology from preclinical models to humans and identifies an ecological network module underlying the association of the gut microbiota with Western dietary habits.

  20. Despite strong behavioral disruption, Delta9-tetrahydrocannabinol does not affect cell proliferation in the adult mouse dentate gyrus.

    Science.gov (United States)

    Kochman, Linda J; dos Santos, Angela Amancio; Fornal, Casimir A; Jacobs, Barry L

    2006-10-01

    Marijuana is a widely abused illicit drug known to cause significant cognitive impairments. Marijuana has been hypothesized to target neurons in the hippocampus because of the abundance of cannabinoid receptors present in this structure. While there is no clear evidence of neuropathology in vivo, suppression of brain mitogenesis, and ultimately neurogenesis, may provide a sensitive index of marijuana's more subtle effects on neural mechanisms subserving cognitive functions. We examined the effects of different doses and treatment regimens of Delta(9)-tetrahydrocannabinol (THC), the main active ingredient in marijuana, on cell proliferation in the dentate gyrus of adult male mice. Following drug treatment, the thymidine analog 5-bromo-2'-deoxyuridine (BrdU; 200 mg/kg, i.p.) was administered two hours prior to sacrifice to assess cell proliferation, the first step in neurogenesis. Administration of THC produced dose-dependent catalepsy and suppression of motor activity. The number of BrdU-labeled cells was not significantly changed from vehicle control levels following either acute (1, 3, 10, 30 mg/kg, i.p.), sequential (two injections of 10 or 30 mg/kg, i.p., separated by 5 h), or chronic escalating (20 to 80 mg/kg, p.o.; for 3 weeks) drug administration. Furthermore, acute administration of the potent synthetic cannabinoid receptor agonist R-(+)-WIN 55,212-2 (WIN; 5 mg/kg, i.p.) also had no significant effect on cell proliferation. These findings provide no evidence for an effect of THC on hippocampal cell proliferation, even at doses producing gross behavioral intoxication. Whether marijuana or THC affects neurogenesis remains to be explored.

  1. Adult mouse subventricular zone stem and progenitor cells are sessile and epidermal growth factor receptor negatively regulates neuroblast migration.

    Directory of Open Access Journals (Sweden)

    Yongsoo Kim

    Full Text Available BACKGROUND: The adult subventricular zone (SVZ contains stem and progenitor cells that generate neuroblasts throughout life. Although it is well accepted that SVZ neuroblasts are migratory, recent evidence suggests their progenitor cells may also exhibit motility. Since stem and progenitor cells are proliferative and multipotential, if they were also able to move would have important implications for SVZ neurogenesis and its potential for repair. METHODOLOGY/PRINCIPAL FINDINGS: We studied whether SVZ stem and/or progenitor cells are motile in transgenic GFP+ slices with two photon time lapse microscopy and post hoc immunohistochemistry. We found that stem and progenitor cells; mGFAP-GFP+ cells, bright nestin-GFP+ cells and Mash1+ cells were stationary in the SVZ and rostral migratory stream (RMS. In our search for motile progenitor cells, we uncovered a population of motile betaIII-tubulin+ neuroblasts that expressed low levels of epidermal growth factor receptor (EGFr. This was intriguing since EGFr drives proliferation in the SVZ and affects migration in other systems. Thus we examined the potential role of EGFr in modulating SVZ migration. Interestingly, EGFr(low neuroblasts moved slower and in more tortuous patterns than EGFr-negative neuroblasts. We next questioned whether EGFr stimulation affects SVZ cell migration by imaging Gad65-GFP+ neuroblasts in the presence of transforming growth factor alpha (TGF-alpha, an EGFr-selective agonist. Indeed, acute exposure to TGF-alpha decreased the percentage of motile cells by approximately 40%. CONCLUSIONS/SIGNIFICANCE: In summary, the present study directly shows that SVZ stem and progenitor cells are static, that EGFr is retained on some neuroblasts, and that EGFr stimulation negatively regulates migration. This result suggests an additional role for EGFr signaling in the SVZ.

  2. Melatonin attenuates methamphetamine-induced inhibition of neurogenesis in the adult mouse hippocampus: An in vivo study.

    Science.gov (United States)

    Singhakumar, Rachen; Boontem, Parichart; Ekthuwapranee, Kasima; Sotthibundhu, Areechun; Mukda, Sujira; Chetsawang, Banthit; Govitrapong, Piyarat

    2015-10-01

    Methamphetamine (METH), a highly addictive psychostimulant drug, is known to exert neurotoxic effects to the dopaminergic neural system. Long-term METH administration impairs brain functions such as cognition, learning and memory. Newly born neurons in the dentate gyrus of the hippocampus play an important role in spatial learning and memory. Previous in vitro studies have shown that METH inhibits cell proliferation and neurogenesis in the hippocampus. On the other hand, melatonin, a major indole secreted by the pineal gland, enhances neurogenesis in both the subventricular zone and dentate gyrus. In this study, adult C57BL/6 mice were used to study the beneficial effects of melatonin on METH-induced alterations in neurogenesis and post-synaptic proteins related to learning and memory functions in the hippocampus. The results showed that METH caused a decrease in neuronal phenotypes as determined by the expressions of nestin, doublecortin (DCX) and beta-III tubulin while causing an increase in glial fibrillary acidic protein (GFAP) expression. Moreover, METH inhibited mitogen-activated protein kinase (MAPK) signaling activity and altered expression of the N-methyl-d-aspartate (NMDA) receptor subunits NR2A and NR2B as well as calcium/calmodulin-dependent protein kinase II (CaMKII). These effects could be attenuated by melatonin pretreatment. In conclusion, melatonin prevented the METH-induced reduction in neurogenesis, increase in astrogliogenesis and alteration of NMDA receptor subunit expression. These findings may indicate the beneficial effects of melatonin on the impairment of learning and memory caused by METH. PMID:26366944

  3. Subchronic inhalation of soluble manganese induces expression of hypoxia-associated angiogenic genes in adult mouse lungs

    International Nuclear Information System (INIS)

    Although the lung constitutes the major exposure route for airborne manganese (Mn), little is known about the potential pulmonary effects and the underlying molecular mechanisms. Transition metals can mimic a hypoxia-like response, activating the hypoxia inducible factor-1 (HIF-1) transcription factor family. Through binding to the hypoxia-response element (HRE), these factors regulate expression of many genes, including vascular endothelial growth factor (VEGF). Increases in VEGF, an important biomarker of angiogenesis, have been linked to respiratory diseases, including pulmonary hypertension. The objective of this study was to evaluate pulmonary hypoxia-associated angiogenic gene expression in response to exposure of soluble Mn(II) and to assess the genes' role as intermediaries of potential pulmonary Mn toxicity. In vitro, 0.25 mM Mn(II) altered morphology and slowed the growth of human pulmonary epithelial cell lines. Acute doses between 0.05 and 1 mM stimulated VEGF promoter activity up to 3.7-fold in transient transfection assays. Deletion of the HRE within the promoter had no effect on Mn(II)-induced VEGF expression but decreased cobalt [Co(II)]-induced activity 2-fold, suggesting that HIF-1 may not be involved in Mn(II)-induced VEGF gene transcription. Nose-only inhalation to 2 mg Mn(II)/m3 for 5 days at 6 h/day produced no significant pulmonary inflammation but induced a 2-fold increase in pulmonary VEGF mRNA levels in adult mice and significantly altered expression of genes associated with murine angiogenesis. These findings suggest that even short-term exposures to soluble, occupationally relevant Mn(II) concentrations may alter pulmonary gene expression in pathways that ultimately could affect the lungs' susceptibility to respiratory disease

  4. Application of a fuzzy neural network model in predicting polycyclic aromatic hydrocarbon-mediated perturbations of the Cyp1b1 transcriptional regulatory network in mouse skin

    Energy Technology Data Exchange (ETDEWEB)

    Larkin, Andrew [Department of Environmental and Molecular Toxicology, Oregon State University (United States); Department of Statistics, Oregon State University (United States); Superfund Research Center, Oregon State University (United States); Siddens, Lisbeth K. [Department of Environmental and Molecular Toxicology, Oregon State University (United States); Superfund Research Center, Oregon State University (United States); Krueger, Sharon K. [Superfund Research Center, Oregon State University (United States); Linus Pauling Institute, Oregon State University (United States); Tilton, Susan C.; Waters, Katrina M. [Superfund Research Center, Oregon State University (United States); Computational Biology and Bioinformatics Group, Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Williams, David E., E-mail: david.williams@oregonstate.edu [Department of Environmental and Molecular Toxicology, Oregon State University (United States); Superfund Research Center, Oregon State University (United States); Linus Pauling Institute, Oregon State University (United States); Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); Baird, William M. [Department of Environmental and Molecular Toxicology, Oregon State University (United States); Superfund Research Center, Oregon State University (United States); Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States)

    2013-03-01

    Polycyclic aromatic hydrocarbons (PAHs) are present in the environment as complex mixtures with components that have diverse carcinogenic potencies and mostly unknown interactive effects. Non-additive PAH interactions have been observed in regulation of cytochrome P450 (CYP) gene expression in the CYP1 family. To better understand and predict biological effects of complex mixtures, such as environmental PAHs, an 11 gene input-1 gene output fuzzy neural network (FNN) was developed for predicting PAH-mediated perturbations of dermal Cyp1b1 transcription in mice. Input values were generalized using fuzzy logic into low, medium, and high fuzzy subsets, and sorted using k-means clustering to create Mamdani logic functions for predicting Cyp1b1 mRNA expression. Model testing was performed with data from microarray analysis of skin samples from FVB/N mice treated with toluene (vehicle control), dibenzo[def,p]chrysene (DBC), benzo[a]pyrene (BaP), or 1 of 3 combinations of diesel particulate extract (DPE), coal tar extract (CTE) and cigarette smoke condensate (CSC) using leave-one-out cross-validation. Predictions were within 1 log{sub 2} fold change unit of microarray data, with the exception of the DBC treatment group, where the unexpected down-regulation of Cyp1b1 expression was predicted but did not reach statistical significance on the microarrays. Adding CTE to DPE was predicted to increase Cyp1b1 expression, whereas adding CSC to CTE and DPE was predicted to have no effect, in agreement with microarray results. The aryl hydrocarbon receptor repressor (Ahrr) was determined to be the most significant input variable for model predictions using back-propagation and normalization of FNN weights. - Highlights: ► Tested a model to predict PAH mixture-mediated changes in Cyp1b1 expression ► Quantitative predictions in agreement with microarrays for Cyp1b1 induction ► Unexpected difference in expression between DBC and other treatments predicted ► Model predictions

  5. Undergraduate Laboratory Module on Skin Diffusion

    Science.gov (United States)

    Norman, James J.; Andrews, Samantha N.; Prausnitz, Mark R.

    2011-01-01

    To introduce students to an application of chemical engineering directly related to human health, we developed an experiment for the unit operations laboratory at Georgia Tech examining diffusion across cadaver skin in the context of transdermal drug delivery. In this laboratory module, students prepare mouse skin samples, set up diffusion cells…

  6. Development of the mouse dermal adipose layer occurs independently of subcutaneous adipose tissue and is marked by restricted early expression of FABP4.

    Science.gov (United States)

    Wojciechowicz, Kamila; Gledhill, Karl; Ambler, Carrie A; Manning, Craig B; Jahoda, Colin A B

    2013-01-01

    The laboratory mouse is a key animal model for studies of adipose biology, metabolism and disease, yet the developmental changes that occur in tissues and cells that become the adipose layer in mouse skin have received little attention. Moreover, the terminology around this adipose body is often confusing, as frequently no distinction is made between adipose tissue within the skin, and so called subcutaneous fat. Here adipocyte development in mouse dorsal skin was investigated from before birth to the end of the first hair follicle growth cycle. Using Oil Red O staining, immunohistochemistry, quantitative RT-PCR and TUNEL staining we confirmed previous observations of a close spatio-temporal link between hair follicle development and the process of adipogenesis. However, unlike previous studies, we observed that the skin adipose layer was created from cells within the lower dermis. By day 16 of embryonic development (e16) the lower dermis was demarcated from the upper dermal layer, and commitment to adipogenesis in the lower dermis was signalled by expression of FABP4, a marker of adipocyte differentiation. In mature mice the skin adipose layer is separated from underlying subcutaneous adipose tissue by the panniculus carnosus. We observed that the skin adipose tissue did not combine or intermix with subcutaneous adipose tissue at any developmental time point. By transplanting skin isolated from e14.5 mice (prior to the start of adipogenesis), under the kidney capsule of adult mice, we showed that skin adipose tissue develops independently and without influence from subcutaneous depots. This study has reinforced the developmental link between hair follicles and skin adipocyte biology. We argue that because skin adipocytes develop from cells within the dermis and independently from subcutaneous adipose tissue, that it is accurately termed dermal adipose tissue and that, in laboratory mice at least, it represents a separate adipose depot.

  7. Noggin and BMP4 co-modulate adult hippocampal neurogenesis in the APPswe/PS1ΔE9 transgenic mouse model of Alzheimer's disease

    International Nuclear Information System (INIS)

    In addition to the subventricular zone, the dentate gyrus of the hippocampus is one of the few brain regions in which neurogenesis continues into adulthood. Perturbation of neurogenesis can alter hippocampal function, and previous studies have shown that neurogenesis is dysregulated in Alzheimer disease (AD) brain. Bone morphogenetic protein-4 (BMP4) and its antagonist Noggin have been shown to play important roles both in embryonic development and in the adult nervous system, and may regulate hippocampal neurogenesis. Previous data indicated that increased expression of BMP4 mRNA within the dentate gyrus might contribute to decreased hippocampal cell proliferation in the APPswe/PS1ΔE9 mouse AD model. However, it is not known whether the BMP antagonist Noggin contributes to the regulation of neurogenesis. We therefore studied the relative expression levels and localization of BMP4 and its antagonist Noggin in the dentate gyrus and whether these correlated with changes in neurogenesis in 6-12 mo old APPswe/PS1ΔE9 transgenic mice. Bromodeoxyuridine (BrdU) was used to label proliferative cells. We report that decreased neurogenesis in the APP/PS1 transgenic mice was accompanied by increased expression of BMP4 and decreased expression of Noggin at both the mRNA and protein levels; statistical analysis showed that the number of proliferative cells at different ages correlated positively with Noggin expression and negatively with BMP4 expression. Intraventricular administration of a chimeric Noggin/Fc protein was used to block the action of endogenous BMP4; this resulted in a significant increase in the number of BrdU-labeled cells in dentate gyrus subgranular zone and hilus in APP/PS1 mice. These results suggest that BMP4 and Noggin co-modulate neurogenesis.

  8. Effects of cyclophosphamide and acrolein in organoid cultures of mouse limb bud cells grown in the presence of adult rat hepatocytes.

    Science.gov (United States)

    Ghaida, J; Merker, H J

    1992-01-01

    The effects were evaluated of cyclophosphamide (CPA) and its metabolite, acrolein, on chondrogenesis in organoid cultures of mouse limb bud mesenchymal cells co-cultured with non-enzymatically isolated adult rat hepatocytes. The studies were conducted with or without the simultaneous addition of 2-mercaptoethanesulphonic acid sodium (mesna) or glutathione (GSH). Alcian blue binding assay and light and electron microscopic techniques were used. Increasing concentrations of the two compounds (bioactivated CPA, 18-180 mum; acrolein, 50-500 mum) led to a dose-dependent inhibition of chondrogenesis associated with cellular dedifferentiation and/or cytotoxicity. Addition of mesna (1 mm) or GSH (1 mm) partially protected the cultures against CPA and acrolein. However, the protective effect depended on the dose of CPA or acrolein used. A higher protection was observed with mesna than with GSH, and the effect was more pronounced with acrolein than with CPA. The morphological findings suggested that CPA and acrolein acted by different mechanisms. Bioactivated CPA primarily inhibited the differentiation process, whereas acrolein exhibited a high cytotoxic activity affecting particularly monolayer cells that normally grow on the periphery of the cultures. These findings suggest that acrolein possesses a specific mode of action directed towards this type of cell. This could be explained by the specific shape and/or behaviour of the cells (i.e. cytoskeletal arrangement, proliferation rate, migration activity, intercellular communication pattern, etc.). The results demonstrated that the cell system used was suitable for the performance of cytotoxicity and teratogenicity studies such as those conducted with CPA and acrolein.

  9. Risk of sensitization in healthy adults following repeated administration of rdESAT-6 skin test reagent by the Mantoux injection technique

    DEFF Research Database (Denmark)

    Lillebaek, Troels; Bergstedt, Winnie; Tingskov, Pernille N;

    2009-01-01

    Limited specificity of the tuberculin skin test incited the development of the intradermal Mycobacterium tuberculosis-specific rdESAT-6 skin test. Animal studies have shown, however, that there is a possible risk of sensitization when repeated injections of rdESAT-6 are given. The aim of this phase...... 31 (3%) volunteers showed a positive skin reaction (sensitization) upon a second injection of rdESAT-6 after 28days and an increased IFN-gamma response to ESAT-6. For 7 (23%) of the volunteers, local adverse reactions related to the product were registered, but all reactions were mild and predictable....... In conclusion, repeated injections of the rdESAT-6 skin test reagent are safe, and sensitization occurs at a low rate, especially if the time span between succeeding doses is wide....

  10. Skin Diseases: Skin Health and Skin Diseases

    Science.gov (United States)

    ... Usually the cause is staphylococcal (staph), but sometimes streptococcus (strep) can cause it, too. It is most ... color or outline, or in any other way. Psoriasis © 2008 Logical Images, Inc. Psoriasis —A skin disease ...

  11. Use of dual section mRNA in situ hybridisation/immunohistochemistry to clarify gene expression patterns during the early stages of nephron development in the embryo and in the mature nephron of the adult mouse kidney.

    Science.gov (United States)

    Georgas, Kylie; Rumballe, Bree; Wilkinson, Lorine; Chiu, Han Sheng; Lesieur, Emmanuelle; Gilbert, Thierry; Little, Melissa H

    2008-11-01

    The kidney is the most complex organ within the urogenital system. The adult mouse kidney contains in excess of 8,000 mature nephrons, each of which can be subdivided into a renal corpuscle and 14 distinct tubular segments. The histological complexity of this organ can make the clarification of the site of gene expression by in situ hybridisation difficult. We have defined a panel of seven antibodies capable of identifying the six stages of early nephron development, the tubular nephron segments and the components of the renal corpuscle within the embryonic and adult mouse kidney. We have analysed in detail the protein expression of Wt1, Calb1 Aqp1, Aqp2 and Umod using these antibodies. We have then coupled immunohistochemistry with RNA in situ hybridisation in order to precisely identify the expression pattern of different genes, including Wnt4, Umod and Spp1. This technique will be invaluable for examining at high resolution, the structure of both the developing and mature nephron where standard in situ hybridisation and histological techniques are insufficient. The use of this technique will enhance the expression analyses of genes which may be involved in nephron formation and the function of the mature nephron in the mouse.

  12. Curious Skin

    OpenAIRE

    Angel, G.

    2010-01-01

    Some of Henry Wellcome’s collection of tattoos on human skin will be on display in our forthcoming Skin exhibition. But how did the Parisian doctor from whom they were acquired come by his macabre collection of tattoos in the first place, and what did they mean to those whose skin they were on? It’s Gemma Angel‘s job to find out…

  13. Histopathologic characterization of the BTBR mouse model of autistic-like behavior reveals selective changes in neurodevelopmental proteins and adult hippocampal neurogenesis

    Directory of Open Access Journals (Sweden)

    Stephenson Diane T

    2011-05-01

    Full Text Available Abstract Background The inbred mouse strain BTBR T+ tf/J (BTBR exhibits behavioral deficits that mimic the core deficits of autism. Neuroanatomically, the BTBR strain is also characterized by a complete absence of the corpus callosum. The goal of this study was to identify novel molecular and cellular changes in the BTBR mouse, focusing on neuronal, synaptic, glial and plasticity markers in the limbic system as a model for identifying putative molecular and cellular substrates associated with autistic behaviors. Methods Forebrains of 8 to 10-week-old male BTBR and age-matched C57Bl/6J control mice were evaluated by immunohistochemistry using free-floating and paraffin embedded sections. Twenty antibodies directed against antigens specific to neurons, synapses and glia were used. Nissl, Timm and acetylcholinesterase (AchE stains were performed to assess cytoarchitecture, mossy fibers and cholinergic fiber density, respectively. In the hippocampus, quantitative stereological estimates for the mitotic marker bromodeoxyuridine (BrdU were performed to determine hippocampal progenitor proliferation, survival and differentiation, and brain-derived neurotrophic factor (BDNF mRNA was quantified by in situ hybridization. Quantitative image analysis was performed for NG2, doublecortin (DCX, NeuroD, GAD67 and Poly-Sialic Acid Neural Cell Adhesion Molecule (PSA-NCAM. Results In midline structures including the region of the absent corpus callosum of BTBR mice, the myelin markers 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase and myelin basic protein (MBP were reduced, and the oligodendrocyte precursor NG2 was increased. MBP and CNPase were expressed in small ectopic white matter bundles within the cingulate cortex. Microglia and astrocytes showed no evidence of gliosis, yet orientations of glial fibers were altered in specific white-matter areas. In the hippocampus, evidence of reduced neurogenesis included significant reductions in the number of

  14. Oily skin

    Science.gov (United States)

    ... keep your skin clean using warm water and soap, or a soapless cleanser. Clean your face with astringent pads if frequent face washing causes irritation. Use only water-based or oil-free cosmetics if you have oily skin. Your ...

  15. Investigation of skin cancer treatment efficiency by raman spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Lee, M. S.; Kim, D. W. [Kyungpook National University, Taegu (Korea)

    2000-04-01

    From the successful perform of the molecular structures of various kinds of human skin cancer. We can predict the types of cancer when a small abnormal change change occurs on skin by raman spectrum. When we applied the cancer causing chemicals, bezopyrene, to nude mouse, it did not develop to cancer. But we had radiated UV light after developed to skin cancer in a few days. We can deduce the development of human skin cancer from the result of nude mouse skin cancer, because the two skin are structurally very similar to each other. From the results of own research we could conform the UV light is essential for the development of skin cancer. The results of own research can be directly apply to early detection and proper treatment of skin cancer in hospital. 32 refs., 40 figs., 16 tabs. (Author)

  16. On-Going Frontal Alpha Rhythms Are Dominant in Passive State and Desynchronize in Active State in Adult Gray Mouse Lemurs

    OpenAIRE

    Francesco Infarinato; Anisur Rahman; Claudio Del Percio; Yves Lamberty; Regis Bordet; Richardson, Jill C.; Gianluigi Forloni; Wilhelmus Drinkenburg; Susanna Lopez; Fabienne Aujard; Claudio Babiloni; Fabien Pifferi

    2015-01-01

    The gray mouse lemur (Microcebus murinus) is considered a useful primate model for translational research. In the framework of IMI PharmaCog project (Grant Agreement n°115009, www.pharmacog.org), we tested the hypothesis that spectral electroencephalographic (EEG) markers of motor and locomotor activity in gray mouse lemurs reflect typical movement-related desynchronization of alpha rhythms (about 8-12 Hz) in humans. To this aim, EEG (bipolar electrodes in frontal cortex) and electromyographi...

  17. Evaluation of clinical use of OneDose™ metal oxide semiconductor field-effect transistor detectors compared to thermoluminescent dosimeters to measure skin dose for adult patients with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Huda Ibrahim Al-Mohammed

    2011-01-01

    Full Text Available Background: Total body irradiation is a protocol used to treat acute lymphoblastic leukemia in patients prior to their bone marrow transplant. It involves the treatment of the whole body using a large radiation field with extended source-skin distance. Therefore, it is important to measure and monitor the skin dose during the treatment. Thermoluminescent dosimeters (TLDs and the OneDose™ metal oxide semiconductor field effect transistor (MOSFET detectors are used during treatment delivery to measure the radiation dose and compare it with the target prescribed dose. Aims: The primary goal of this study was to measure the variation of skin dose using OneDose MOSFET detectors and TLD detectors, and compare the results with the target prescribed dose. The secondary aim was to evaluate the simplicity of use and determine if one system was superior to the other in clinical use. Material and Methods : The measurements involved twelve adult patients diagnosed with acute lymphoblastic leukemia. TLD and OneDose MOSFET dosimetry were performed at ten different anatomical sites of each patient. Results : The results showed that there was a variation between skin dose measured with OneDose MOSFET detectors and TLD in all patients. However, the variation was not significant. Furthermore, the results showed for every anatomical site there was no significant different between the prescribed dose and the dose measured by either TLD or OneDose MOSFET detectors. Conclusion: There were no significant differences between the OneDose MOSFET and TLDs in comparison to the target prescribed dose. However, OneDose MOSFET detectors give a direct read-out immediately after the treatment, and their simplicity of use to compare with TLD detectors may make them preferred for clinical use.

  18. Culture and establishment of self-renewing human and mouse adult liver and pancreas 3D organoids and their genetic manipulation

    NARCIS (Netherlands)

    Broutier, Laura; Andersson-Rolf, Amanda; Hindley, Christopher J; Boj, Sylvia F; Clevers, Hans; Koo, Bon-Kyoung; Huch, Meritxell

    2016-01-01

    Adult somatic tissues have proven difficult to expand in vitro, largely because of the complexity of recreating appropriate environmental signals in culture. We have overcome this problem recently and developed culture conditions for adult stem cells that allow the long-term expansion of adult prima

  19. Skin Cancer in Skin of Color

    OpenAIRE

    Bradford, Porcia T.

    2009-01-01

    Skin cancers in skin of color often present atypically or with advanced stage in comparison to Caucasian patients. Health care providers must maintain a high index of suspicion when examining skin lesions in skin of color.

  20. Skin abscess

    Science.gov (United States)

    ... infection (often staphylococcus) A minor wound or injury Boils Folliculitis (infection in a hair follicle) A skin ... Elsevier Churchill Livingstone; 2009:chap 90. Read More Boils Endocarditis Folliculitis MRSA Osteomyelitis Update Date 11/12/ ...

  1. Skin graft

    Science.gov (United States)

    ... caused a large amount of skin loss Burns Cosmetic reasons or reconstructive surgeries where there has been ... Smoking increases your chance of problems such as slow healing. Ask your doctor or nurse for help ...

  2. Skin Pigment

    Science.gov (United States)

    ... This Article Medical Dictionary Also of Interest (Quiz) Vitiligo (Video) Hives Additional Content Medical News Overview of ... Version Pigment Disorders Overview of Skin Pigment Albinism Vitiligo Hyperpigmentation Melasma Melanin is the brown pigment that ...

  3. Skin Cancer Screening

    Science.gov (United States)

    ... Genetics of Skin Cancer Skin Cancer Screening Research Skin Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Skin Cancer Key Points Skin cancer is a disease in ...

  4. The effects of X-rays on the mitotic activity of mouse epidermis

    Energy Technology Data Exchange (ETDEWEB)

    Knowlton, N.P. Jr.; Hempelmann, L.H.; Hoffman, J.G.

    1949-04-19

    This report describes a simplified technique of obtaining the mitotic index of mouse skin and indicates the surprising sensitivity of the mitotic activity of mouse epithelium to the effects of x-rays.

  5. A skin-inspired organic digital mechanoreceptor

    Science.gov (United States)

    Tee, Benjamin C.-K.; Chortos, Alex; Berndt, Andre; Nguyen, Amanda Kim; Tom, Ariane; McGuire, Allister; Lin, Ziliang Carter; Tien, Kevin; Bae, Won-Gyu; Wang, Huiliang; Mei, Ping; Chou, Ho-Hsiu; Cui, Bianxiao; Deisseroth, Karl; Ng, Tse Nga; Bao, Zhenan

    2015-10-01

    Human skin relies on cutaneous receptors that output digital signals for tactile sensing in which the intensity of stimulation is converted to a series of voltage pulses. We present a power-efficient skin-inspired mechanoreceptor with a flexible organic transistor circuit that transduces pressure into digital frequency signals directly. The output frequency ranges between 0 and 200 hertz, with a sublinear response to increasing force stimuli that mimics slow-adapting skin mechanoreceptors. The output of the sensors was further used to stimulate optogenetically engineered mouse somatosensory neurons of mouse cortex in vitro, achieving stimulated pulses in accordance with pressure levels. This work represents a step toward the design and use of large-area organic electronic skins with neural-integrated touch feedback for replacement limbs.

  6. Innate lymphoid cells and the skin

    OpenAIRE

    Salimi, Maryam; Ogg, Graham

    2014-01-01

    Innate lymphoid cells are an emerging family of effector cells that contribute to lymphoid organogenesis, metabolism, tissue remodelling and protection against infections. They maintain homeostatic immunity at barrier surfaces such as lung, skin and gut (Nature 464:1367–1371, 2010, Nat Rev Immunol 13: 145–149, 2013). Several human and mouse studies suggest a role for innate lymphoid cells in inflammatory skin conditions including atopic eczema and psoriasis. Here we review the innate lymphoid...

  7. Effective Isolation and Propagation of Adult Mouse Spermatogonial Stem Cells in vitro%一种有效分离及在体外扩增成年小鼠精原干细胞的方法

    Institute of Scientific and Technical Information of China (English)

    冉竞超; 曹文广; 孙红艳; 王令; 辛颖; 张智英

    2012-01-01

    尝试建立一种简便有效的成年小鼠精原干细胞分离培养及扩增的方法.从单只成年小鼠的睾丸中经过两步酶消化法分离精原干细胞,并在去除间质细胞、纯化后的支持细胞饲养层上培养与扩增,获得稳定增殖的精原干细胞系.此方法可显著提高建系成功率,保证细胞系的单一基因型,显著降低体外培养精原干细胞的成本.为成体基因来源的转基因动物的制作和疾病模型的建立提供技术支持.%In our study, we established a convenient and effective method for isolating and propagating the adult spermatogonial stem cells in vitro. We isolated the spermatogonial stem cells from the testes of one adult KM mouse by two-step digestion, and then cultured the cells on the purified Sertoli cells treated with mitomycin-C, eventually we established the stable adult spermatogonial stem cell lines. Our study increased the efficiency of cell line establishment prominently, guaranteed to achieve the single genotype cell line, and reduced the cost of culturing adult male germline stem cells in vitro. This method provided the foundation for producing the transgenic animals and disease models derived from adult genotype.

  8. 金雀异黄素对D-半乳糖损伤的乳鼠皮肤成纤维细胞的作用%Study of genistein on mouse skin fibroblasts injured by D-galactose

    Institute of Scientific and Technical Information of China (English)

    顾翠英; 韩志芬; 夏花英; 蒋嘉烨; 曹红平; 金国琴

    2012-01-01

    Objective To observe the effects of genistein (Gen) on the mouse skin fibroblasts (MSFs) injured by D-galactose and investigate the mechanisms. Methods MSFs were cultured in vitro, then Gen was used to affect the model cells injured by D-galactose. The morphostructure of the MSFs were observed with microscope. The vitalities of superoxide dismutase ( SOD) , lactic acid dehydrogenase (LDH) , and the content of malondialdehyde (MDA) were measured by kit methods. Erαand ERβmRNA were detected by RT-PCR method. Results Compared with model group, 0. 5 mg/L Gen could improve the content of MDA, increase the vitalities of SOD and LDH (P < 0.01) markedly. Gen could decrease the expression of Erα mRNA (P<0. 05) and increase Erβ mRNA (P<0. 05) obviously. Conclusions 0. 5 mg/L Gen can improve ER mRNA, enhance the vitality of SOD and antioxidation, increase the content of MDA and the vitality of LDH, change the biological characteristics of MSFs, inhibit MSFs proliferation.%目的 观察金雀异黄素(Gen)对D-半乳糖(D-gal)损伤的小鼠皮肤成纤维细胞(MSFs)模型的作用,并探索其机制.方法 体外培养MSFs,D-gal制作细胞损伤模型,并用Gen进行干预.显微镜下观察各组MSFs生长形态变化;试剂盒法检测MSFs上清液中超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量和乳酸脱氢酶(LDH)活性;RT-PCR法检测MSFs的雌激素受体雌激素受体(ER)α和ERβ mRNA的表达.结果 与模型组相比,浓度为0.5 mg/L Gen能显著提高SOD活性,同时亦提高MDA含量和LDH活性(P<0.01);明显下调ERα mRNA表达(P<0.05),上调ERβmRNA表达(P<0.05).结论 浓度为0.5 mg/L Gen可以通过改善模型细胞ER mRNA的表达,提高SOD活性和抗氧化作用;同时升高MDA含量和LDH活性,改变MSFs的生物学特性,抑制其过度增殖.

  9. Therapeutic potential of a non-steroidal bifunctional anti-inflammatory and anti-cholinergic agent against skin injury induced by sulfur mustard

    International Nuclear Information System (INIS)

    Sulfur mustard (bis(2-chloroethyl) sulfide, SM) is a highly reactive bifunctional alkylating agent inducing edema, inflammation, and the formation of fluid-filled blisters in the skin. Medical countermeasures against SM-induced cutaneous injury have yet to be established. In the present studies, we tested a novel, bifunctional anti-inflammatory prodrug (NDH 4338) designed to target cyclooxygenase 2 (COX2), an enzyme that generates inflammatory eicosanoids, and acetylcholinesterase, an enzyme mediating activation of cholinergic inflammatory pathways in a model of SM-induced skin injury. Adult SKH-1 hairless male mice were exposed to SM using a dorsal skin vapor cup model. NDH 4338 was applied topically to the skin 24, 48, and 72 h post-SM exposure. After 96 h, SM was found to induce skin injury characterized by edema, epidermal hyperplasia, loss of the differentiation marker, keratin 10 (K10), upregulation of the skin wound marker keratin 6 (K6), disruption of the basement membrane anchoring protein laminin 322, and increased expression of epidermal COX2. NDH 4338 post-treatment reduced SM-induced dermal edema and enhanced skin re-epithelialization. This was associated with a reduction in COX2 expression, increased K10 expression in the suprabasal epidermis, and reduced expression of K6. NDH 4338 also restored basement membrane integrity, as evidenced by continuous expression of laminin 332 at the dermal–epidermal junction. Taken together, these data indicate that a bifunctional anti-inflammatory prodrug stimulates repair of SM induced skin injury and may be useful as a medical countermeasure. - Highlights: • Bifunctional anti-inflammatory prodrug (NDH4338) tested on SM exposed mouse skin • The prodrug NDH4338 was designed to target COX2 and acetylcholinesterase. • The application of NDH4338 improved cutaneous wound repair after SM induced injury. • NDH4338 treatment demonstrated a reduction in COX2 expression on SM injured skin. • Changes of skin repair

  10. Therapeutic potential of a non-steroidal bifunctional anti-inflammatory and anti-cholinergic agent against skin injury induced by sulfur mustard

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Yoke-Chen; Wang, James D.; Hahn, Rita A.; Gordon, Marion K.; Joseph, Laurie B. [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Heck, Diane E. [Department of Environmental Science, New York Medical College, Valhalla, NY (United States); Heindel, Ned D. [Department of Chemistry, Lehigh University, Bethlehem, PA (United States); Young, Sherri C. [Department of Chemistry, Muhlenberg College, Allentown, PA (United States); Sinko, Patrick J. [Department of Pharmaceutics, Rutgers University, Piscataway, NJ (United States); Casillas, Robert P. [MRIGlobal, Kansas City, MO (United States); Laskin, Jeffrey D. [Environmental and Occupational Medicine, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ (United States); Laskin, Debra L. [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Gerecke, Donald R., E-mail: gerecke@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States)

    2014-10-15

    Sulfur mustard (bis(2-chloroethyl) sulfide, SM) is a highly reactive bifunctional alkylating agent inducing edema, inflammation, and the formation of fluid-filled blisters in the skin. Medical countermeasures against SM-induced cutaneous injury have yet to be established. In the present studies, we tested a novel, bifunctional anti-inflammatory prodrug (NDH 4338) designed to target cyclooxygenase 2 (COX2), an enzyme that generates inflammatory eicosanoids, and acetylcholinesterase, an enzyme mediating activation of cholinergic inflammatory pathways in a model of SM-induced skin injury. Adult SKH-1 hairless male mice were exposed to SM using a dorsal skin vapor cup model. NDH 4338 was applied topically to the skin 24, 48, and 72 h post-SM exposure. After 96 h, SM was found to induce skin injury characterized by edema, epidermal hyperplasia, loss of the differentiation marker, keratin 10 (K10), upregulation of the skin wound marker keratin 6 (K6), disruption of the basement membrane anchoring protein laminin 322, and increased expression of epidermal COX2. NDH 4338 post-treatment reduced SM-induced dermal edema and enhanced skin re-epithelialization. This was associated with a reduction in COX2 expression, increased K10 expression in the suprabasal epidermis, and reduced expression of K6. NDH 4338 also restored basement membrane integrity, as evidenced by continuous expression of laminin 332 at the dermal–epidermal junction. Taken together, these data indicate that a bifunctional anti-inflammatory prodrug stimulates repair of SM induced skin injury and may be useful as a medical countermeasure. - Highlights: • Bifunctional anti-inflammatory prodrug (NDH4338) tested on SM exposed mouse skin • The prodrug NDH4338 was designed to target COX2 and acetylcholinesterase. • The application of NDH4338 improved cutaneous wound repair after SM induced injury. • NDH4338 treatment demonstrated a reduction in COX2 expression on SM injured skin. • Changes of skin repair

  11. Dynamic, Sex-Differential STAT5 and BCL6 Binding to Sex-Biased, Growth Hormone-Regulated Genes in Adult Mouse Liver

    OpenAIRE

    Zhang, Yijing; Laz, Ekaterina V.; Waxman, David J.

    2012-01-01

    Sex-dependent pituitary growth hormone (GH) secretory patterns determine the sex-biased expression of >1,000 genes in mouse and rat liver, affecting lipid and drug metabolism, inflammation, and disease. A fundamental biological question is how robust differential expression can be achieved for hundreds of sex-biased genes simply based on the GH input signal pattern: pulsatile GH stimulation in males versus near-continuous GH exposure in females. STAT5 is an essential transcriptional mediator ...

  12. Vibrotactile Presentation of Musical Notes to the Glabrous Skin for Adults with Normal Hearing or a Hearing Impairment: Thresholds, Dynamic Range and High-Frequency Perception

    Science.gov (United States)

    Maté-Cid, Saúl; Fulford, Robert; Seiffert, Gary; Ginsborg, Jane

    2016-01-01

    Presentation of music as vibration to the skin has the potential to facilitate interaction between musicians with hearing impairments and other musicians during group performance. Vibrotactile thresholds have been determined to assess the potential for vibrotactile presentation of music to the glabrous skin of the fingertip, forefoot and heel. No significant differences were found between the thresholds for sinusoids representing notes between C1 and C6 when presented to the fingertip of participants with normal hearing and with a severe or profound hearing loss. For participants with normal hearing, thresholds for notes between C1 and C6 showed the characteristic U-shape curve for the fingertip, but not for the forefoot and heel. Compared to the fingertip, the forefoot had lower thresholds between C1 and C3, and the heel had lower thresholds between C1 and G2; this is attributed to spatial summation from the Pacinian receptors over the larger contactor area used for the forefoot and heel. Participants with normal hearing assessed the perception of high-frequency vibration using 1s sinusoids presented to the fingertip and were found to be more aware of transient vibration at the beginning and/or end of notes between G4 and C6 when stimuli were presented 10dB above threshold, rather than at threshold. An average of 94% of these participants reported feeling continuous vibration between G4 and G5 with stimuli presented 10dB above threshold. Based on the experimental findings and consideration of health effects relating to vibration exposure, a suitable range of notes for vibrotactile presentation of music is identified as being from C1 to G5. This is more limited than for human hearing but the fundamental frequencies of the human voice, and the notes played by many instruments, lie within it. However, the dynamic range might require compression to avoid the negative effects of amplitude on pitch perception. PMID:27191400

  13. Vibrotactile Presentation of Musical Notes to the Glabrous Skin for Adults with Normal Hearing or a Hearing Impairment: Thresholds, Dynamic Range and High-Frequency Perception.

    Directory of Open Access Journals (Sweden)

    Carl Hopkins

    Full Text Available Presentation of music as vibration to the skin has the potential to facilitate interaction between musicians with hearing impairments and other musicians during group performance. Vibrotactile thresholds have been determined to assess the potential for vibrotactile presentation of music to the glabrous skin of the fingertip, forefoot and heel. No significant differences were found between the thresholds for sinusoids representing notes between C1 and C6 when presented to the fingertip of participants with normal hearing and with a severe or profound hearing loss. For participants with normal hearing, thresholds for notes between C1 and C6 showed the characteristic U-shape curve for the fingertip, but not for the forefoot and heel. Compared to the fingertip, the forefoot had lower thresholds between C1 and C3, and the heel had lower thresholds between C1 and G2; this is attributed to spatial summation from the Pacinian receptors over the larger contactor area used for the forefoot and heel. Participants with normal hearing assessed the perception of high-frequency vibration using 1s sinusoids presented to the fingertip and were found to be more aware of transient vibration at the beginning and/or end of notes between G4 and C6 when stimuli were presented 10dB above threshold, rather than at threshold. An average of 94% of these participants reported feeling continuous vibration between G4 and G5 with stimuli presented 10dB above threshold. Based on the experimental findings and consideration of health effects relating to vibration exposure, a suitable range of notes for vibrotactile presentation of music is identified as being from C1 to G5. This is more limited than for human hearing but the fundamental frequencies of the human voice, and the notes played by many instruments, lie within it. However, the dynamic range might require compression to avoid the negative effects of amplitude on pitch perception.

  14. Distribution of immunoreactive glutamine synthetase in the adult human and mouse brain. Qualitative and quantitative observations with special emphasis on extra-astroglial protein localization.

    Science.gov (United States)

    Bernstein, Hans-Gert; Bannier, Jana; Meyer-Lotz, Gabriela; Steiner, Johann; Keilhoff, Gerburg; Dobrowolny, Henrik; Walter, Martin; Bogerts, Bernhard

    2014-11-01

    Glutamine synthetase catalyzes the ATP-dependent condensation of ammonia and glutamate to form glutamine, thus playing a pivotal role in glutamate and glutamine homoeostasis. Despite a plethora of studies on this enzyme, knowledge about the regional and cellular distribution of this enzyme in human brain is still fragmentary. Therefore, we mapped fourteen post-mortem brains of psychically healthy individuals for the distribution of the glutamine synthetase immunoreactive protein. It was found that glutamine synthetase immunoreactivity is expressed in multiple gray and white matter astrocytes, but also in oligodendrocytes, ependymal cells and certain neurons. Since a possible extra-astrocytic expression of glutamine synthetase is highly controversial, we paid special attention to its appearance in oligodendrocytes and neurons. By double immunolabeling of mouse brain slices and cultured mouse brain cells for glutamine synthetase and cell-type-specific markers we provide evidence that besides astrocytes subpopulations of oligodendrocytes, microglial cells and neurons express glutamine synthetase. Moreover, we show that glutamine synthetase-immunopositive neurons are not randomly distributed throughout human and mouse brain, but represent a subpopulation of nitrergic (i.e. neuronal nitric oxide synthase expressing) neurons. Possible functional implications of an extra-astrocytic localization of glutamine synthetase are discussed.

  15. TSLP is differentially regulated by vitamin D3 and cytokines in human skin

    OpenAIRE

    Landheer, Janneke; Giovannone, Barbara; Sadekova, Svetlana; Tjabringa, Sandra; Hofstra, Claudia; Dechering, Koen; Bruijnzeel-Koomen, Carla; Chang, Charlie; Ying, Yu; de Waal Malefyt, Rene; Hijnen, DirkJan; Knol, Edward

    2015-01-01

    Thymic stromal lymphopoietin (TSLP) plays an important role in allergic diseases and is highly expressed in keratinocytes in human lesional atopic dermatitis (AD) skin. In nonlesional AD skin TSLP expression can be induced by applying house dust mite allergen onto the skin in the atopy patch test. Several studies have demonstrated that the induction of TSLP expression in mouse skin does not only lead to AD-like inflammation of the skin, but also predisposes to severe inflammation of the airwa...

  16. Characteristics of Adult T-Cell Leukemia/Lymphoma Patients with Long Survival: Prognostic Significance of Skin Lesions and Possible Beneficial Role of Valproic Acid

    OpenAIRE

    Plumelle Yves; Michel Stephane; Banydeen Rishika; Delaunay Christine; Panelatti Gérard

    2015-01-01

    We describe the clinical and biological features of ten patients with a survival superior to ten years (long survival), out of 175 patients diagnosed with Adult T-cell Leukemia/Lymphoma (ATL) in Martinique (1983–2013). There were 5 lymphoma and 5 chronic subtypes. Five of them (3 chronic, 2 lymphoma) had been treated with valproic acid (VA) for neurological disorders developed before or after ATL diagnosis, suggesting a beneficial role for VA as a histone deacetylase inhibitor (HDI) in ATL tr...

  17. Skin Care and Aging

    Science.gov (United States)

    ... page please turn Javascript on. Skin Care and Aging How Aging Affects Skin Your skin changes with age. It ... if they bother you. See additional resources on aging skin, including information on treatment options, specific conditions, ...

  18. Skin Cancer Foundation

    Science.gov (United States)

    ... Host a Fundraising Event | About Us | Store The Skin Cancer Foundation The Skin Cancer Foundation is the ... A "Sunscreen Gene"? Skin Cancer Facts & Statistics The Skin Cancer Foundation's Champions for Change Gala 2016 Learn ...

  19. Skin Pigmentation Disorders

    Science.gov (United States)

    Pigmentation means coloring. Skin pigmentation disorders affect the color of your skin. Your skin gets its color from a pigment called melanin. Special cells in the skin make melanin. When these cells become damaged or ...

  20. First genomic survey of human skin fungal diversity

    Science.gov (United States)

    Fungal infections of the skin affect 29 million people in the United States. In the first study of human fungal skin diversity, National Institutes of Health researchers sequenced the DNA of fungi that thrive at different skin sites of healthy adults to d

  1. Skin Substitutes

    OpenAIRE

    Zavan, Barbara; Vindigni, Vincenzo; Cortivo, Roberta; Abatangelo, Giovanni

    2010-01-01

    The many studies conducted so far reveal that Tissue Engineering of the skin is only at the beginning of its use in human applications. Burns patients were the first targets for such tissue substitutes, then chronic diseases, such as venous ulcers, have followed. The more experience is gained from the surgeon, the more feedback for the basic scientist to improve the product and to broaden clinical indications. Nowadays, progress in cell culture and biomedical material technologies have added ...

  2. Skin aging:

    OpenAIRE

    Puizina-Ivić, Neira

    2008-01-01

    There are two main processes that induce skin aging: intrinsic and extrinsic. A stochastic process that implies random cell damage as a result of mutations during metabolic processes due to the production of free radicals is also implicated. Extrinsic aging is caused by environmental factors such as sun exposure, air pollution, smoking, alcohol abuse, and poor nutrition. Intrinsicaging reflects the genetic background and depends on time. Various expressions of intrinsic aging include smooth, ...

  3. Mouse adhalin

    DEFF Research Database (Denmark)

    Liu, L; Vachon, P H; Kuang, W;

    1997-01-01

    analyze the biological roles of adhalin, we cloned the mouse adhalin cDNA, raised peptide-specific antibodies to its cytoplasmic domain, and examined its expression and localization in vivo and in vitro. The mouse adhalin sequence was 80% identical to that of human, rabbit, and hamster. Adhalin was...... specifically expressed in striated muscle cells and their immediate precursors, and absent in many other cell types. Adhalin expression in embryonic mouse muscle was coincident with primary myogenesis. Its expression was found to be up-regulated at mRNA and protein levels during myogenic differentiation in...

  4. Distribution and antimicrobial susceptibility of bacteria from adults with community-acquired pneumonia or complicated skin and soft tissue infections in France: the nationwide French PREMIUM study.

    Science.gov (United States)

    Leprince, C; Desroches, M; Emirian, A; Coutureau, C; Anais, L; Fihman, V; Soussy, C J; Decousser, J W

    2015-10-01

    The empirical therapy of community-acquired pneumonia (CAP) and complicated skin and soft tissue infections (cSSTIs) must be based on updated bacterial distribution and susceptibility data. A nationwide study consecutively collected 1288 isolates from CAP (n=467) and cSSTIs (n=821) from 18 French hospitals between 2012 and 2013. The MIC values of commonly used antimicrobial agents, including ceftaroline, were determined. Bacterial distribution featured Pneumococcus, Haemophilus influenzae, and Staphylococcus aureus for CAPs and S. aureus, β-hemolytic streptococci and Enterobacteriaceae for cSSTIs. Antimicrobial susceptibility testing indicated i) the sustained third-generation cephalosporins and levofloxacin activity against pneumococci and H. influenzae, ii) no methicillin-resistant Staphylococcus aureus emergence among respiratory pathogens, iii) the high in vitro activity of ceftaroline against staphylococci from cSSTIs (98.7% susceptibility), and iv) the worrisome decreasing fluoroquinolone and third-generation cephalosporin susceptibilities among Enterobacteriaceae. This laboratory-based survey depicts a contrasting situation and supports the scoring of patients for the resistant pathogen risk before empirical therapy. PMID:26166208

  5. Assessing the effects of a short-term green tea intervention in skin microvascular function and oxygen tension in older and younger adults.

    Science.gov (United States)

    Wasilewski, Rebecca; Ubara, Emmanuel O; Klonizakis, Markos

    2016-09-01

    Green tea consumption has been associated with a reduction in cardiovascular disease risk factors. However, there is little evidence examining its potential differing effect between younger and older populations, whilst little is known on its effect on the circulatory system when oxygen demand is higher. Therefore the aim of this study was to evaluate the short-term effects of green tea consumption on microvascular functioning in both an older and younger population. Fifteen young [24 (4.0)] and fifteen older [61 (4.0)] participants, consumed two cups of green tea daily for 14days. We used Laser Doppler Flowmetry (LDF) to assess cutaneous microvascular function and Transcutaneous Oxygen monitoring (TcPO2) to assess skin oxygen tension. Systolic and diastolic blood pressure were also assessed on both visits. We observed significant improvements in axon-mediated microvascular vasodilation for the younger group [1.6 (0.59) vs 2.05 (0.72), pgreen tea may prove beneficial as a dietary element in lifestyle interventions aiming to lower cardiovascular disease risk, in both older and younger populations. PMID:27165772

  6. Cutaneous skin tag

    Science.gov (United States)

    Skin tag; Acrochordon; Fibroepithelial polyp ... have diabetes. They are thought to occur from skin rubbing against skin. ... The tag sticks out of the skin and may have a short, narrow stalk connecting it to the surface of the skin. Some skin tags are as long as ...

  7. Intrinsic properties of lumbar motor neurones in the adult G127insTGGG superoxide dismutase-1 mutant mouse in vivo: evidence for increased persistent inward currents

    DEFF Research Database (Denmark)

    Meehan, Claire Francesca; Moldovan, Mihai; Marklund, Stefan L.;

    2010-01-01

    of lumbar motoneurones in the adult presymptomatic G127X mutant are not significantly different from those of wild type. However, at more depolarized membrane potentials, motoneurones in the G127X SOD1 mutants can sustain higher frequency firing, showing less spike frequency adaption and with persistent...... inward currents (PICs) being activated at lower firing frequencies and being more pronounced. Conclusion: We demonstrated that, in vivo, at resting membrane potential, spinal motoneurones of the adult G127X mice do not show an increased excitability. However, when depolarized they show evidence...

  8. Research on skin surface hardness variation of the adult males with different body fat rate%不同体脂率成年男性人体皮肤表面硬度差异研究

    Institute of Scientific and Technical Information of China (English)

    王旭; 卜伟平; 柳松杨; 杨阳; 丛红

    2013-01-01

    Objective To investigate the variation of skin surface hardness at different body part of the adult males with different body fat rate and to present the reference to the design of the skin and muscle of dynamic simulation dummyn.Methods Thirty subjects were divided into two groups,the normal group (body fat rate <20%) and the obese group (body fat rate ≥20%).Type A Shore meter was used to test the skin surface hardness at 28 parts of body and sebum thickness caliper was used to test skinfold thickness at 2 parts of body.Statistical analysis of different parts' hardness of 30 subjects was accomplished by using K-related Samples and the significant level was detected by using 2-related Samples.Independent-Samples t Test was used to test the difference between normal group and obese group with a level of significance set as P<0.05.The relationship between skin hardness and body fat rate was also analyzed.Results Sixteen subjects were grouped as normal while the rest 14 were in obese based on body fat rate measurement.From the results we observed statistical significant hardness differences at 22 parts of body between 2 groups (t=1.885~5.865,P<0.05).Specifically,the hardness of medial limbs was significantly lower than that of lateral limbs' (P<0.05) and the hardness of mid shanks was significantly greater than that of other parts of body (P<0.05).Furthermore,the hardness of medial thigh and hip was equal to zero.In both groups,there was significant correlation between body fat rate and skinfold thickness.Conclusions The skin surface hardness shows similar distribution but significant variation in the adult males with different body fat rate.Body fat rate,as an important factor depending the skin hardness,should be taken into consideration when we design the skin and muscle of dynamic simulation dummy.%目的 通过测量人体皮肤表面硬度及体脂率,研究不同体脂率的人及不同身体部位的皮肤硬度的差异,为航空动态仿

  9. Adult glucocorticoid exposure leads to transcriptional and DNA methylation changes in nuclear steroid receptors in the hippocampus and kidney of mouse male offspring.

    Science.gov (United States)

    Petropoulos, Sophie; Matthews, Stephen G; Szyf, Moshe

    2014-02-01

    Synthetic glucocorticoids (sGCs) are commonly prescribed for the management of inflammatory and endocrine disorders. However, nothing is known regarding the effects of sGC on adult germline methylome and whether these effects can be transmitted to the next generation. We hypothesized that administration of sGC to adult male mice alters DNA methylation in mature sperm and modifies the transcription and methylation of steroid receptors in male F1 offspring. Adult C57BL/6 males (n = 10/group) were injected on five consecutive days with 1 mg/kg sGC (i.e., dexamethasone) or vehicle and euthanized 35 or 60 days after initial treatment or bred with control females (60 days postinitial treatment; n = 5/group). A significant increase in global non-CpG methylation was observed in F0 sperm 60 days following sGC treatment. In the hippocampus and kidney of Postnatal Day 50 (PND50) and PND240 male offspring derived from fathers exposed to sGC, significant differences in mineralocorticoid receptor (Nr3c2; Mr), estrogen alpha receptor (Nr3a1; Ers1), and glucocorticoid receptor (Nr3c1; Gr) expression were observed. Furthermore, significant demethylation in regulatory regions of Mr, Gr, and Esr1 was observed in the PND50 kidney derived from fathers exposed to sGC. This is the first demonstration that paternal pharmacological exposure to sGC can alter the expression and DNA methylation of nuclear steroid receptors in brain and somatic tissues of offspring. These findings provide proof of principle that adult male exposure to sGC can affect DNA methylation and gene expression in offspring, indicating the possibility that adult experiences that evoke increases in endogenous glucocorticoid (i.e., stress) might have similar effects.

  10. Gesture Recognition Based Mouse Events

    Directory of Open Access Journals (Sweden)

    Rachit Puri

    2013-12-01

    Full Text Available This paper presents the maneuver of mouse pointer a nd performs various mouse operations such as left click, right click, double click, drag etc using ge stures recognition technique. Recognizing gestures is a complex task which involves many aspects such as mo tion modeling, motion analysis, pattern recognition and machine learning. Keeping all the essential factors in mind a system has been created which recognizes the movement of fingers and various patterns formed by them. Color caps have been used for fingers to distinguish it f rom the background color such as skin color. Thus recog nizing the gestures various mouse events have been performed. The application has been created on MATL AB environment with operating system as windows 7.

  11. κ-卡拉胶寡糖对小鼠皮肤成纤维细胞增殖和胶原分泌的影响%Effects of κ-carrageenan oligosaccharides on cell proliferation and collagen secretion in cultured mouse skin fibroblast

    Institute of Scientific and Technical Information of China (English)

    王天琦; 吴海歌; 姚子昂

    2013-01-01

    目的研究κ-卡拉胶寡糖对小鼠皮肤成纤维细胞增殖和胶原分泌的影响.方法原代培养小鼠皮肤成纤维细胞,传代培养后加入不同浓度的κ-卡拉胶寡糖作用,应用细胞计数法,四甲基偶氮唑盐(MTT)比色法,检测κ--卡拉胶寡糖对皮肤成纤维细胞增殖的影响,ELISA法检测κ--卡拉胶寡糖对皮肤成纤维细胞分泌Ⅰ型、Ⅲ型胶原蛋白的影响.结果12.5μg/mL~100μg,/mL