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Rab25 Deficiency Perturbs Epidermal Differentiation and Skin Barrier Function in Mice

  • Jeong, Haengdueng;Lim, Kyung-Min;Goldenring, James R.;Nam, Ki Taek
    • Biomolecules & Therapeutics
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    • v.27 no.6
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    • pp.553-561
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    • 2019
  • Rab25, a member of the Rab11 small GTPase family, is central to achieving cellular polarity in epithelial tissues. Rab25 is highly expressed in epithelial cells of various tissues including breast, vagina, cervix, the gastrointestinal tract, and skin. Rab25 plays key roles in tumorigenesis, mainly by regulating epithelial differentiation and proliferation. However, its role in skin physiology is relatively unknown. In this study, we demonstrated that Rab25 knock-out (KO) mice show a skin barrier dysfunction with high trans-epidermal water loss and low cutaneous hydration. To examine this observation, we investigated the histology and epidermal differentiation markers of the skin in Rab25 KO mice. Rab25 KO increased cell proliferation at the basal layer of epidermis, whereas the supra-basal layer remained unaffected. Ceramide, which is a critical lipid component for skin barrier function, was not altered by Rab25 KO in its distribution or amount, as determined by immunohistochemistry. Notably, levels of epidermal differentiation markers, including loricrin, involucrin, and keratins (5, 14, 1, and 10) increased prominently in Rab25 KO mice. In line with this, depletion of Rab25 with single hairpin RNA increased the expression of differentiation markers in a human keratinocyte cell line, HaCaT. Transcriptomic analysis of the skin revealed increased expression of genes associated with skin development, epidermal development, and keratinocyte differentiation in Rab25 KO mice. Collectively, these results suggested that Rab25 is involved in the regulation of epidermal differentiation and proliferation.

Toxicological Evaluation of Phytochemical Characterized Aqueous Extract of Wild Dried Lentinus squarrosulus (Mont.) Mushroom in Rats

  • Ugbogu, Eziuche Amadike;Akubugwo, Iroha Emmanuel;Ude, Victor Chibueze;Gilbert, James;Ekeanyanwu, Blessing
    • Toxicological Research
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    • v.35 no.2
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    • pp.181-190
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    • 2019
  • Lentinus squarrosulus (Mont.) is an edible wild mushroom with tough fruiting body that belongs to the family Polyporaceae. It is used in ethnomedicine for the treatment of ulcer, anaemia, cough and fever. Recent studies have demonstrated its anticancer, anti-diabetic and antioxidant properties. However, little or no information is available regarding the bioactive components and toxicological study of wild dried L. squarrosulus. Therefore, this study investigated the bioactive components of aqueous extract of boiled wild dried L. squarrosulus and its toxicological effects in rats. The extract of L. squarrosulus was subjected to GC-MS analysis. The acute toxicity test was performed by oral administration of a single dose of up to 5,000 mg/kg extract of L. squarrosulus. In subacute study, the rats were orally administered extract of L. squarrosulus at the doses of 500, 1,000 and 1,500 mg/kg body weight daily for 14 days. The haematological, lipid profile, liver and kidney function parameters were determined and the histopathology of the liver and kidney were examined. The GC-MS analysis revealed the presence of bioactive compounds; 1-tetradecene, fumaric acid, monochloride, 6-ethyloct-3-yl ester, 9-eicosene, phytol, octahydropyrrolo[1,2-a]pyrazine and 3-trifluoroacetoxypentadecane. In acute toxicity study, neither death nor toxicity sign was recorded. In the sub-acute toxicity study, significant differences (p < 0.05) were observed on creatinine, aspartate aminotransferase, alanine aminotransferase, total cholesterol, triglycerides and high-density lipoprotein cholesterol. Whilst no significant differences (p > 0.05) were observed on packed cell volume, heamoglobin, red blood cell, white blood cell and alkaline phosphatase, in all the tested doses. No histopathological alterations were recorded. Our findings revealed that aqueous extract of L. squarrosulus may have antimicrobial, antinocieptive and antioxidant properties based on the result of GC-MS analysis. Results of the toxicity test showed no deleterious effect at the tested doses, suggesting that L. squarrosulus is safe for consumption at the tested doses.

Molecular Phylogeny of the Amynthas-complex (Oligochaeta: Megascolecidae) Inferred from ITS Nucleotide Sequences (Ribosomal DNA ITS 유전자를 이용한 왕지렁이(빈모강: 지렁이과) 그룹의 계통분류)

  • Hong, Yong;James, Samuel W.;Hwang, Ui-Wook;Lee, Bo-Eun;Park, Soon-Cheol;Kim, Tae-Heung
    • Korean Journal of Environmental Biology
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    • v.25 no.4
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    • pp.349-355
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    • 2007
  • Phylogeny of the species mainly from the genus Amynthas in family Megascolecidae was inferred at the molecular level using ITS regions in rDNA. With 26 species of earthworms from 10 genera in 2 families, a stretch comprising the 3'-end of the 18S rRNA, ITS1, 5.8S rRNA, ITS2, and 5' end of 28S rRNA was amplified by applying the primers ITS-1, ITS-2. Phylogenetic analyses of nucleotide sequences with a help of MP, NJ, and QP yielded 5 groups similarly. Genus Amynthas was separated largely into two groups, Korean and Philippine origins. Species grouped into the 1st were Amynthas jirensis, A. agrestis, A. gucheonensis, A. sopaikensis, A. bubonis, A. multimaculatus, A. koreanus, A. dageletensis, A. heteropodus, A. odaesanensis, Pontoscolex sp., Pheretima sp. 1, and Dendropheretima banahawensis. Amynthas halconensis, A. isarogensis, A. mindrooensis, Pithemera sp. 2, Pithmera sp. 1, and Pleionogaster sp. clustered into one clade forming the 2nd group. Polypheretima sp. 1 and polypheretima. sp. 2 stayed closely together representing a separate monophyletic status, forming the 3rd group, apart from species in other genera. Archipheretima sp. falls into the 4th group. Distinct morphological characteristics from Archipheretima also coinsides with its branching away from others in the previously reported molecular analyses. Similar to Perionyx excavatus that has been selected as an outgroup, Aporrectodea tuberculata also showed a long branch in the phylogram, but it differed from other 24 species included in the analyses. Unlike others, for example, its habitat is very closely related to that of man.

American Culture at the Crossroad : Debates over NEA(National Endowments for the Arts) (미국 문화, 그 기로에 서서 - NEA(국립예술진흥기금)를 둘러싼 논쟁 중심으로)

  • Kim, Jin-A
    • The Journal of Art Theory & Practice
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    • no.4
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    • pp.33-56
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    • 2006
  • The cultural debates between conservatives and liberals at the end of the 1980s and in the early 1990s were termed as "culture wars." The "culture wars" involved a diverse range of controversial issues, such as the introduction of multicultural curricula in educational institutions, prayers in schools, whether to allow gays to serve openly in the military, and whether abortion should be permitted. The most heated debates of the "culture wars" regarding art raged over the NEA and the question of whether Andres Serrano's works should have been publicly funded, in addition to the exhibition "Robert Mapplethorpe: The Perfect Moment" which were charged as projecting "obscene" or "blasphemous" images. This paper examines the development of culture wars in art and focuses on several issues invoked by the NEA debates. However, it is not a detailed chronological investigation. Rather it pays attention to the several phases of the debates, analyzing and criticizing the clashes of the political and esthetical points of views between conservatives and liberals. How could NEA funding, a mere fraction of the federal budget, have become so critical for both sides(conservative and liberal), for politicians and artists' groups, and for academics and the general public? The art community was astounded by this chain of events; artists personally reviled, exhibitions withdrawn and under attack, the NEA budget threatened, all because of a few images. For conservative politicians, the NEA debate was not only a battle over the public funding of art, but a war over a larger social agenda, a war for "American values and cultures"based on the family, Christianity, the English language, and patriarchy. Conservative politicians argued the question was not one of "censorship" but of "sponsorship," since the NEA charter committed it to "helping museums better serve the citizens of the United States."Liberals and art communities argued that the attempt to restrict NEA funding violated the First Amendment rights of artists, namely "free speeches." "No matter how divided individuals are on matters of taste," Arthur C. Danto wrote, "freedom is in the interest of every citizen." The interesting phase is that both sides are actually borrowing one another's point of view when they are accompanied by art criticism. Kramer, representative of conservative art critic, objected the invasion of political contents or values in art, and struggled to keep art's own realm by promoting pure aesthetic values such as quality and beauty. But, when he talked about Mapplethorpe's works, he advocated political and ethical values. By contrast, art experts who argued for Mapplethorpe's works in the Cincinnati trial defended his work, ironically by ignoring its manifest sexual metaphor or content although they believed that the issues of AIDS and homosexuality in his work were to be freely expressed in the art form. They adopted a formalistic approach, for example, by comparing a child nude with putti, a traditional child-angel icon. For a while, NEA debates made art institutions, whether consciously or unconsciously, exert self-censorship, yet at the same time they were also producing positive aspects. To the majority of people, art was still regarded as belonging to the pure aesthetic realm away from political, economical, and social ones. These debates, however, were expanding the very perspective on the notion of what is art and of how art is produced, raising questions on art appreciation, representation, and power. The interesting fact remains: had the works not been swiped in NEA debates, could the Serrano's or Mapplethorpe's images gain the extent of power and acceptance that it has today?

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