Maalikunstnik Olav Marani traditsioonilises laadis loodud vaikelude kunstilisest mudelist ja teostes väljenduvast esteetilisest ja eetilisest kvaliteedist. Ka natüürmordi kui žanri eripärast, eelkäijatest kunstiajaloos, Marani erinevusest neist ning tema kui religioosse kunstniku elufilosoofiast ja võtetest, mille abil ta seda on väljendanud
Kuony, Alison; Michon, Frederic
As an element of the lacrimal apparatus, the lacrimal gland (LG) produces the aqueous part of the tear film, which protects the eye surface. Therefore, a defective LG can lead to serious eyesight impairment. Up to now, little is known about LG morphogenesis and subsequent maturation. In this study, we delineated elements of the cellular and molecular events involved in LG formation by using three epithelial markers, namely aSMA, Krt14, and Krt19. While aSMA marked a restricted epithelial population of the terminal end buds (TEBs) in the forming LG, Krt14 was found in the whole embryonic LG epithelial basal cell layer. Interestingly, Krt19 specifically labeled the presumptive ductal domain and subsequently, the luminal cell layer. By combining these markers, the Fucci reporter mouse strain and genetic fate mapping of the Krt14 + population, we demonstrated that LG epithelium expansion is fuelled by a patterned cell proliferation, and to a lesser extent by epithelial reorganization and possible mesenchymal-to-epithelial transition. We pointed out that this epithelial reorganization, which is associated with apoptosis, regulated the lumen formation. Finally, we showed that the inhibition of Notch signaling prevented the ductal identity from setting, and led to a LG covered by ectopic TEBs. Taken together our results bring a deeper understanding on LG morphogenesis, epithelial domain identity, and organ expansion.
Om Olav Tryggvessons berømte skib Ormen Lange og de meget store skibe fra omkring år 1000 og begyndelsen af 1000-årene, som nu kendes arkæologisk. Og om kong Olavs legendariske færdigheder i sværdleg og at kunne løbe på et skibs årer...
Høystad, Ole Martin
Artiklen diskuterer sammenhængen mellem kærlighed, (erotisk) lidenskab og ondskab i Sigrid Undsets og Olav Duuns digtning. Artiklen lavet på grundlag af foredrag - i anledning 100-årsjubilæet for to digteres debuter - på Norsk Litteraturfestival/Sigrid Undset-dagene på Lillehammer i 2007....
Thomer, Annika; Gottschalk, Maren; Christmann, Anna; Naccache, Fanny; Jung, Klaus; Hewicker-Trautwein, Marion; Distl, Ottmar; Metzger, Julia
Curly coat represents an extraordinary type of coat in horses, particularly seen in American Bashkir Curly Horses and Missouri Foxtrotters. In some horses with curly coat, a hypotrichosis of variable extent was observed, making the phenotype appear more complex. In our study, we aimed at investigating the genetic background of curly coat with and without hypotrichosis using high density bead chip genotype and next generation sequencing data. Genome-wide association analysis detected significant signals (p = 1.412 × 10 -05 -1.102 × 10 -08 ) on horse chromosome 11 at 22-35 Mb. In this significantly associated region, six missense variants were filtered out from whole-genome sequencing data of three curly coated horses of which two variants within KRT25 and SP6 could explain all hair phenotypes. Horses heterozygous or homozygous only for KRT25 variant showed curly coat and hypotrichosis, whereas horses with SP6 variant only, exhibited curly coat without hypotrichosis. Horses with mutant alleles in both variants developed curly hair and hypotrichosis. Thus, mutant KRT25 allele is masking SP6 allele effect, indicative for epistasis of KRT25 variant over SP6 variant. In summary, genetic variants in two different genes, KRT25 and SP6, are responsible for curly hair. All horses with KRT25 variant are additionally hypotrichotic due to the KRT25 epistatic effect on SP6.
Wu, Huijuan; Wang, Ke; Liu, Wenxin; Hao, Quan
Highlights: • Overexpression of PTEN enhanced the sensitivity of C13K cells to cisplatin. • KRT10 is a downstream molecule of PTEN involved in the resistance-reversing effect. • Overexpression of KRT10 enhanced the chemosensitivity of C13K cells to cisplatin. - Abstract: Multi-drug resistance (MDR) is a common cause of the failure of chemotherapy in ovarian cancer. PTEN, a tumor suppressor gene, has been demonstrated to be able to reverse cisplatin-resistance in ovarian cancer cell line C13K. However, the downstream molecules of PTEN involved in the resistance-reversing effect have not been completely clarified. Therefore, we screened the downstream molecules of PTEN and studied their interactions in C13K ovarian cancer cells using a 3D culture model. Firstly, we constructed an ovarian cancer cell line stably expressing PTEN, C13K/PTEN. MTT assay showed that overexpression of PTEN enhanced the sensitivity of C13K cells to cisplatin, but not to paclitaxel. Then we examined the differently expressed proteins that interacted with PTEN in C13K/PTEN cells with or without cisplatin treatment by co-immunoprecipitation. KRT10 was identified as a differently expressed protein in cisplatin-treated C13K/PTEN cells. Further study confirmed that cisplatin could induce upregulation of KRT10 mRNA and protein in C13K/PTEN cells and there was a directly interaction between KRT10 and PTEN. Forced expression of KRT10 in C13K cells also enhanced cisplatin-induced proliferation inhibition and apoptosis of C13K cells. In addition, KRT10 siRNA blocked cisplatin-induced proliferation inhibition of C13K/PTEN cells. In conclusion, our data demonstrate that KRT10 is a downstream molecule of PTEN which improves cisplatin-resistance of ovarian cancer and forced KRT10 overexpression may also act as a therapeutic method for overcoming MDR in ovarian cancer
Birkenkamp-Demtröder, Karin; Hahn, Stephan; Mansilla, Francisco
correlated with absent expression, while increased KRT23 expression in tumor samples correlated with promoter hypomethylation, as confirmed by bisulfite sequencing. Demethylation induced KRT23 expression in vitro. Expression profiling of shRNA mediated stable KRT23 knockdown in colon cancer cell lines showed...... response, mainly molecules of the double strand break repair homologous recombination pathway. KRT23 knockdown decreased the transcript and protein expression of key molecules as e.g. MRE11A, E2F1, RAD51 and BRCA1. Knockdown of KRT23 rendered colon cancer cells more sensitive to irradiation and reduced......Keratin 23 (KRT23) is strongly expressed in colon adenocarcinomas but absent in normal colon mucosa. Array based methylation profiling of 40 colon samples showed that the promoter of KRT23 was methylated in normal colon mucosa, while hypomethylated in most adenocarcinomas. Promoter methylation...
Full Text Available Keratin 23 (KRT23 is strongly expressed in colon adenocarcinomas but absent in normal colon mucosa. Array based methylation profiling of 40 colon samples showed that the promoter of KRT23 was methylated in normal colon mucosa, while hypomethylated in most adenocarcinomas. Promoter methylation correlated with absent expression, while increased KRT23 expression in tumor samples correlated with promoter hypomethylation, as confirmed by bisulfite sequencing. Demethylation induced KRT23 expression in vitro. Expression profiling of shRNA mediated stable KRT23 knockdown in colon cancer cell lines showed that KRT23 depletion affected molecules of the cell cycle and DNA replication, recombination and repair. In vitro analyses confirmed that KRT23 depletion significantly decreased the cellular proliferation of SW948 and LS1034 cells and markedly decreased the expression of genes involved in DNA damage response, mainly molecules of the double strand break repair homologous recombination pathway. KRT23 knockdown decreased the transcript and protein expression of key molecules as e.g. MRE11A, E2F1, RAD51 and BRCA1. Knockdown of KRT23 rendered colon cancer cells more sensitive to irradiation and reduced proliferation of the KRT23 depleted cells compared to irradiated control cells.
Satoh, Akira; Mitogawa, Kazumasa; Saito, Nanami; Suzuki, Miyuki; Suzuki, Ken-Ichi T; Ochi, Haruki; Makanae, Aki
Limb regeneration is considered a form of limb redevelopment because of the molecular and morphological similarities. Forming a regeneration blastema is, in essence, creating a developing limb bud in an adult body. This reactivation of a developmental process in a mature body is worth studying. Xenopus laevis has a biphasic life cycle that involves distinct larval and adult stages. These distinct developmental stages are useful for investigating the reactivation of developmental processes in post-metamorphic frogs (froglets). In this study, we focused on the re-expression of a larval gene (krt62.L) during Xenopus froglet limb regeneration. Recently renamed krt62.L, this gene was known as the larval keratin (xlk) gene, which is specific to larval-tadpole stages. During limb regeneration in a froglet, krt62.L was re-expressed in a basal layer of blastema epithelium, where adult-specific keratin (Krt12.6.S) expression was also observable. Nerves produce important regulatory factors for amphibian limb regeneration, and also play a role in blastema formation and maintenance. The effect of nerve function on krt62.L expression could be seen in the maintenance of krt62.L expression, but not in its induction. When an epidermis-stripped limb bud was grafted in a froglet blastema, the grafted limb bud could reach the digit-forming stage. This suggests that krt62.L-positive froglet blastema epithelium is able to support the limb development process. These findings imply that the developmental process is locally reactivated in an postmetamorphic body during limb regeneration. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Sun Yuanjun; Zhang Renyan; Zhao Weijun
In the design of KRT system in Ling Ao Ⅱ, it requires the hardware composition shall be similar to that of Ling Ao Ⅰ. At the same time, the KRT system should be digitized and centralized. In order to realize the goal, the KRT system will be divided into the lower and upper parts. The local sensor at the lower part will transform the analog signal to digital signal in the local display unit; then the digital signals are sent to the upper part (cabinet) by RS-485; the cabinet collects the signals, saves and displays them in the server or operation workstation. or sends them to the DCS. On the other hand, the digital signals will be treated into analog or on/off signals in cabinet and transmitted to other systems. (authors)
Syéd, Grethe Fatima
This dissertation discusses questions regarding love, suicide, art and transgression in the work of Olav Duun (1876-1939). The main theses are that there is an attitude worth searching for in Duun's work, and that this attitude expresses a caring which the concept of love is better suited to describe than terms taken from a philosophical ethics. Furthermore, I hold that the much discussed ethics in Duun's work is inseparable from the aesthetics, understood as having to do with beauty, art and...
Full Text Available Efforts to develop effective therapeutic treatments for promoting fast wound healing after injury to the epidermis are hindered by a lack of understanding of the factors involved. Re-epithelialization is an essential step of wound healing involving the migration of epidermal keratinocytes over the wound site. Here, we examine genetic variants in the keratin-1 (KRT1 locus for association with migration rates of human epidermal keratinocytes (HEK isolated from different individuals. Although the role of intermediate filament genes, including KRT1, in wound activated keratinocytes is well established, this is the first study to examine if genetic variants in humans contribute to differences in the migration rates of these cells. Using an in vitro scratch wound assay we observe quantifiable variation in HEK migration rates in two independent sets of samples; 24 samples in the first set and 17 samples in the second set. We analyze genetic variants in the KRT1 interval and identify SNPs significantly associated with HEK migration rates in both samples sets. Additionally, we show in the first set of samples that the average migration rate of HEK cells homozygous for one common haplotype pattern in the KRT1 interval is significantly faster than that of HEK cells homozygous for a second common haplotype pattern. Our study demonstrates that genetic variants in the KRT1 interval contribute to quantifiable differences in the migration rates of keratinocytes isolated from different individuals. Furthermore we show that in vitro cell assays can successfully be used to deconstruct complex traits into simple biological model systems for genetic association studies.
Thomas S. Worst
Full Text Available Purpose. To validate microarray data on cytokeratin 13 (KRT13 and interleukin-1 receptor antagonist (IL1RN expression in urothelial carcinoma of the urinary bladder (UCB and to correlate our findings with pathologic characteristics and tobacco smoking. Methods. UCB tissue samples (n=109 and control samples (n=14 were obtained from transurethral resection and radical cystectomy specimens. Immunohistochemical staining of KRT13 and IL1RN was performed and semiquantitative expression scores were assessed. Smoking status was evaluated using a standardized questionnaire. Expression scores were correlated with pathologic characteristics (tumor stage and grade and with smoking status. Results. Loss of KRT13 and IL1RN expression was observed in UCB tissue samples when compared to controls (P=0.007, P=0.008 in which KRT13 and IL1RN expression were high. IL1RN expression was significantly reduced in muscle-invasive tumors (P=0.003. In tissue samples of current smokers, a significant downregulation of IL1RN was found when compared to never smokers (P=0.013. Conclusion. Decreased expressions of KRT13 and IL1RN are common features of UCB and are associated with aggressive disease. Tobacco smoking may enhance the loss of IL1RN, indicating an overweight of proinflammatory mediators involved in UCB progression. Further validation of the influence of smoking on IL1RN expression is warranted.
Kim, Kyeongseok; Yang, Gwang-Mo; Choi, Hye Yeon
Cytokeratin 19 (KRT19) is a cytoplasmic intermediate filament protein, which is responsible for structural rigidity and multipurpose scaffolds. In several cancers, KRT19 is overexpressed and may play a crucial role in tumorigenic transformation. In our previous study, we revealed the role of KRT19 as signaling component which mediated Wnt/NOTCH crosstalk through NUMB transcription in breast cancer. Here, we investigated the function of KRT19 in cancer reprogramming and drug resistance in breast cancer cells. We found that expression of KRT19 was attenuated in several patients-derived breast cancer tissues and patients with a low expression of KRT19 were significantly correlated with poor prognosis in breast cancer patients. Consistently, highly aggressive and drug-resistant breast cancer patient-derived cancer stem cell-like cells (konkuk university-cancer stem cell-like cell (KU-CSLCs)) displayed higher expression of cancer stem cell (CSC) markers, including ALDH1, CXCR4, and CD133, but a much lower expression of KRT19 than that is seen in highly aggressive triple negative breast cancer MDA-MB231 cells. Moreover, we revealed that the knockdown of KRT19 in MDA-MB231 cells led to an enhancement of cancer properties, such as cell proliferation, sphere formation, migration, and drug resistance, while the overexpression of KRT19 in KU-CSLCs resulted in the significant attenuation of cancer properties. KRT19 regulated cancer stem cell reprogramming by modulating the expression of cancer stem cell markers (ALDH1, CXCR4, and CD133), as well as the phosphorylation of Src and GSK3β (Tyr216). Therefore, our data may imply that the modulation of KRT19 expression could be involved in cancer stem cell reprogramming and drug sensitivity, which might have clinical implications for cancer or cancer stem cell treatment. PMID:29747452
Saha, Subbroto Kumar; Kim, Kyeongseok; Yang, Gwang-Mo; Choi, Hye Yeon; Cho, Ssang-Goo
Cytokeratin 19 ( KRT19 ) is a cytoplasmic intermediate filament protein, which is responsible for structural rigidity and multipurpose scaffolds. In several cancers, KRT19 is overexpressed and may play a crucial role in tumorigenic transformation. In our previous study, we revealed the role of KRT19 as signaling component which mediated Wnt/NOTCH crosstalk through NUMB transcription in breast cancer. Here, we investigated the function of KRT19 in cancer reprogramming and drug resistance in breast cancer cells. We found that expression of KRT19 was attenuated in several patients-derived breast cancer tissues and patients with a low expression of KRT19 were significantly correlated with poor prognosis in breast cancer patients. Consistently, highly aggressive and drug-resistant breast cancer patient-derived cancer stem cell-like cells (konkuk university-cancer stem cell-like cell (KU-CSLCs)) displayed higher expression of cancer stem cell (CSC) markers, including ALDH1 , CXCR4 , and CD133 , but a much lower expression of KRT19 than that is seen in highly aggressive triple negative breast cancer MDA-MB231 cells. Moreover, we revealed that the knockdown of KRT19 in MDA-MB231 cells led to an enhancement of cancer properties, such as cell proliferation, sphere formation, migration, and drug resistance, while the overexpression of KRT19 in KU-CSLCs resulted in the significant attenuation of cancer properties. KRT19 regulated cancer stem cell reprogramming by modulating the expression of cancer stem cell markers ( ALDH1 , CXCR4 , and CD133 ), as well as the phosphorylation of Src and GSK3β (Tyr216). Therefore, our data may imply that the modulation of KRT19 expression could be involved in cancer stem cell reprogramming and drug sensitivity, which might have clinical implications for cancer or cancer stem cell treatment.
Wu, H; Wang, K; Liu, W; Hao, Q
Drug resistance is a major cause of treatment failure in ovarian cancer patients, and novel therapeutic strategies are urgently needed. Overexpression of phosphatase and tensin homolog (PTEN) has been shown to preserve the cisplatin-resistance of ovarian cancer cells, while cisplatin-induced keratin 10 (KRT10) overexpression mediates the resistance-reversing effect of PTEN. However, whether overexpression of PTEN or KRT10 can improve the cisplatin resistance of ovarian cancer in vivo has not been investigated. Therefore, we investigated the effects of adenovirus-mediated PTEN or KRT10 overexpression on the cisplatin resistance of ovarian cancer in vivo. Recombinant adenoviruses carrying the gene for PTEN or KRT10 were constructed. The effects of overexpression of PTEN and KRT10 on cisplatin resistance of ovarian cancer cells were examined using the 3(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT) and TdT-mediated dUTP nick-end labeling (TUNEL) assays in vitro. Subcutaneously transplanted nude mice, as a model of human ovarian cancer, were used to test the effects of PTEN and KRT10 on cisplatin resistance of ovarian cancer in vivo. The MTT assay showed that recombinant adenovirus-mediated overexpression of KRT10 and PTEN enhanced the proliferation inhibition effect of cisplatin on C13K cells. Recombinant adenovirus-mediated overexpression of KRT10 and PTEN also increased the cisplatin-induced apoptosis rate of C13K cells. Furthermore, recombinant adenovirus-mediated overexpression of KRT10 and PTEN enhanced the inhibitory effect of cisplatin on C13K xenograft tumor growth. Thus, recombinant adenovirus-mediated overexpression of KRT10 and PTEN may improve the cisplatin resistance of ovarian cancer in vitro and in vivo.
Miura, Hirohito; Kusakabe, Yuko; Hashido, Kento; Hino, Akihiro; Ooki, Makoto; Harada, Shuitsu
Tastants reach the tip of taste bud cells through taste pores which are openings in the epithelium. We found Sprr2a is selectively expressed in the upper layer of the epithelium surrounding taste buds in the circumvallate papilla (CV) where the epithelium is organized into taste pores. Sprr2a is a member of a small proline-rich protein family, which is suggested to be involved in the restitution/migration phase of epithelial wound healing. The expression of Sprr2a was restricted to the upper layer and largely segregated with Ptch1 expression that is restricted to the basal side of the epithelium around the taste buds. Denervation resulted in the gradual loss of Sprr2a-expressing cells over 10 days similarly to that of taste bud cells which is in contrast to the rapid loss of Ptch1 expression. We also found that denervation caused an increase of Keratin (Krt)13 expression around taste buds that corresponded with the disappearance of Sprr2a and Ptch1 expression. Taste buds were surrounded by Krt13-negative cells in the CV in control mice. However, at 6 days post-denervation, taste buds were tightly surrounded by Krt13-positive cells. During taste bud development, taste bud cells emerged together with Krt13-negtive cells, and Sprr2a expression was increased along with the progress of taste bud development. These results demonstrate that regional gene expression surrounding taste buds is associated with taste bud formation and controlled by the innervating taste nerve. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Chen Siang Ng
Full Text Available Feathers have complex forms and are an excellent model to study the development and evolution of morphologies. Existing chicken feather mutants are especially useful for identifying genetic determinants of feather formation. This study focused on the gene F, underlying the frizzle feather trait that has a characteristic curled feather rachis and barbs in domestic chickens. Our developmental biology studies identified defects in feather medulla formation, and physical studies revealed that the frizzle feather curls in a stepwise manner. The frizzle gene is transmitted in an autosomal incomplete dominant mode. A whole-genome linkage scan of five pedigrees with 2678 SNPs revealed association of the frizzle locus with a keratin gene-enriched region within the linkage group E22C19W28_E50C23. Sequence analyses of the keratin gene cluster identified a 69 bp in-frame deletion in a conserved region of KRT75, an α-keratin gene. Retroviral-mediated expression of the mutated F cDNA in the wild-type rectrix qualitatively changed the bending of the rachis with some features of frizzle feathers including irregular kinks, severe bending near their distal ends, and substantially higher variations among samples in comparison to normal feathers. These results confirmed KRT75 as the F gene. This study demonstrates the potential of our approach for identifying genetic determinants of feather forms.
Verma, Shyam; Pasternack, Sandra M.; Rütten, Arno; Ruzicka, Thomas; Betz, Regina C.; Hanneken, Sandra
Galli Galli disease (GGD) is the name given to a rare form of acantholytic Dowling-Degos disease. (DDD), the latter itself being a rare condition. We believe we are describing for the first time in Indian dermatologic literature a case of GGD in a family where 25 persons have DDD and have been able to document a KRT5 mutation in four members of the family. Whereas reticulate pigmentation is a hallmark of DDD there are rare reports of mottled pigmentation with multiple asymptomatic hypopigmented macules scattered diffusely along with the pigmentation. All the cases described here show a mottled pigmentation comprising hypo and hyperpigmented asymptomatic macules. After the clinical diagnosis was made by one of the authors (SV) in India, the German authors repeated histological examination and successfully demonstrated a heterozygous nonsense mutation, c.C10T (p.Gln4X), in exon 1 of the KRT5 gene, from various centers in Munich, Bonn, Dusseldorf and Friedrichschafen in Germany. PMID:25284854
Courtney, D G; Moore, J E; Atkinson, S D; Maurizi, E; Allen, E H A; Pedrioli, D M L; McLean, W H I; Nesbit, M A; Moore, C B T
CRISPR/Cas9-based therapeutics hold the possibility for permanent treatment of genetic disease. The potency and specificity of this system has been used to target dominantly inherited conditions caused by heterozygous missense mutations through inclusion of the mutated base in the short-guide RNA (sgRNA) sequence. This research evaluates a novel approach for targeting heterozygous single-nucleotide polymorphisms (SNPs) using CRISPR/Cas9. We determined that a mutation within KRT12, which causes Meesmann's epithelial corneal dystrophy (MECD), leads to the occurrence of a novel protospacer adjacent motif (PAM). We designed an sgRNA complementary to the sequence adjacent to this SNP-derived PAM and evaluated its potency and allele specificity both in vitro and in vivo. This sgRNA was found to be highly effective at reducing the expression of mutant KRT12 mRNA and protein in vitro. To assess its activity in vivo we injected a combined Cas9/sgRNA expression construct into the corneal stroma of a humanized MECD mouse model. Sequence analysis of corneal genomic DNA revealed non-homologous end-joining repair resulting in frame-shifting deletions within the mutant KRT12 allele. This study is the first to demonstrate in vivo gene editing of a heterozygous disease-causing SNP that results in a novel PAM, further highlighting the potential for CRISPR/Cas9-based therapeutics.
Os instrumentos de regulação baseados no conhecimento: o caso do programme for international student assessment (PISA Knowledge-based regulation tools (KRT: the programme for international student assessment (PISA case
Full Text Available Este artigo inscreve-se na temática dos novos modos de regulação da educação, em particular nos instrumentos de políticas públicas. No quadro da instrumentação da acção pública, a atenção recai nos instrumentos de regulação baseados no conhecimento (Knowledge-based Regulation Tools [KRT]. Na verdade, a economia mundial fundamenta-se, cada vez mais, no conhecimento, o qual emerge como instrumento de política, regulando os actores sociais e legitimando a decisão política. O Programme for International Student Assessment (PISA, da Organização para Cooperação e Desenvolvimento Económico (OCDE, foi o instrumento escolhido como passível de configurar um KRT. O texto baseiase em seis estudos de caso, assentes em entrevistas e análise documental. Intentando na circulação e no uso do PISA, na Bélgica, Escócia, França, Hungria, Portugal e Roménia, procuramos demonstrar que o PISA se afirma como um KRT, provando a relação circular entre conhecimento e política, dado que, como instrumento de política, produz conhecimento e, como instrumento científico, produz política.This text focuses on the study of a KRT (Knowledgebased Regulation Tool, within the wider framework of the new modes of regulation in education, and use of instruments in public action. The world economy is gradually more knowledge-based. Knowledge emerges as a tool for policy-making and for regulating social actors, and legitimating the political decision-making. We choose the OECD's Program for International Student Assessment (PISA as an example of a KRT. The article is based on six case-studies, with interviews and document analysis. Our goal was to study the circulation and use of PISA, in Belgium, Scotland, France, Hungary, Portugal and Romania, trying to show that PISA is indeed a KRT, thus proving the circular relationship between knowledge and policy, because as a policy instrument it produces knowledge, and as a scientific tool it produces policy.
Aarna, Olav, 1942-
Ilmunud ka: Lääne Elu 31. mai, lk. 2, Põhjarannik 31. mai, lk. 2, Severnoje Poberezhje 31. mai, lk. 2, Meie Maa 31. mai, lk.2, Sakala 1. juuni lk. 2, Nädaline, Lõunaleht, Koit 2. juuni lk. 2,2,6, Kuulutaja 3. juuni lk. 4, Valgamaalane 4. juuni lk. 2. Kordusartikkel Meie Maa 15. juuni lk. 2. Kahest Res Publica poolt algatatud eelnõust koolikorralduse muutmiseks
Aarna, Olav, 1942-
Ilmunud ka: Võrumaa Teataja, 5. okt. 2004, lk. 2; Vali Uudised, 6. okt. 2004, lk. 2; Põhjarannik, 6. okt. 2004, lk. 2; Severnoje Poberezhje, 6. okt. 2004, lk. 2; Nädaline, 7. okt. 2004, lk. 5; Lääne Elu, 7. okt. 2004, lk. 2; Koit, 7. okt. 2004, lk. 6; Hiiu Leht, 8. okt. 2004, lk. 2; Meie Maa, 9. okt. 2004, lk. 2; Sakala, 14. okt. 2004, lk. 2. Hariduskorraldusest Eestis, vaidlused käivad autori sõnul kahe leeri vahel
Aarna, Olav, 1942-
Ilmunud ka: Järva Teataja 1. september lk. 2, Meie Maa 1. september lk. 2, Koit 1. september lk. 6, Severnoje Poberezhje 1. september lk. 2, Vali Uudised 2. september lk. 2, Sakala 2. september lk. 2, Hiiu Leht 2. september lk. 2, Kuulutaja 2. september lk. 4, Nädaline 8. september lk. 4. Riigikogu kultuurikomisjoni esimehe sõnul peaks igaüks sõnastama enda jaoks rahuldava vastuse küsimusele, mis on hea haridus
Eesti Põllumajandus-Kaubanduskoja poolt 30. jaanuaril 2004. a. Haapsalus korraldatud seminarist, kus tutvustati Taani ja Belgia põllumajandusorganisatsioone ning Euroopa põllumajandusorganisatsiooni COPA/COGECA
Aarna, Olav, 1942-
Autori sõnul on ühiskonnas kujunemas selge arusaam, et rahvusliku innovatsioonisüsteemi osaks oleval haridussüsteemil on arengumudeli muutmisel täita võtmeroll. Graafik: Eesti arengustsenaariumid. Tabel: Eesti haridusstsenaariumid
14.-18. märtsini toimus Tallinnas ajalooõpetajate assotsiatsiooni EUROCLIO (European Standing Conference of History Teachers Association) aastakonverents, kuhu saabus üle saja külalise 37 riigist. Konverentsi aruteluteema oli igapäevaelu käsitlemine ajalooõpetuses. 13. märtsil oli haridusministeeriumis minister Tõnis Lukase vastuvõtt õpilaste kodu-uurimuslikust võistlusest osa võtnud tublimatele õpilastele ja nende juhendajatele ning õpetajatele. 1999/2000. õa viidi Körberi Sihtasutuse ja Eesti Ajalooõpetajate Seltsi korraldatud õpilaste ajaloo-alaste uurimistööde võistlus läbi esimest korda. Teemaks oli "Eesti kodu ja pere XX sajandil". 2000. a kuulutati välja uus võistlus teemal "Eesti kool".
Full Text Available nd Neonatal Diseases and Abnormalities (C16) > Congenital Abnormalities (C16.131) > Skin Abnormalities (C16....ases, Inborn (C16.320) > Skin Diseases, Genetic (C16.320.850) > Epidermolysis Bullosa (C16.320.850.275) > Ep...idermolysis Bullosa Simplex (C16.320.850.275.180) Skin and Connective Tissue Diseases (C17) > Skin Diseases (C17.800) > Skin....493) > Epidermolysis Bullosa Simplex (C17.800.804.493.180) Skin and Connective Tissue Diseases (C17) > Skin Diseases (C17.800) > Ski...rmolysis Bullosa Simplex (C17.800.827.275.180) Skin and Connective Tissue Diseases (C17) > Skin
Ehala, Olav, 1950-
"Thijl Ulenspiegeli" lavastustest Eestis, heliplaadist "Thijl Ulenspiegel ja teisi laule". Plaadil esitavad O. Ehala muusikat Tallinna Linnateatri näitlejad Tallinna Kammerorkestri saatel. CD-plaadile salvestatud laule sai kuulda kontsertidel "Tallinna Linnateatel laulab. Õnnelik õhtu"
29. sept.̀2000 toimus Haridusministeeriumis Õppurite Nõukogu istung, kus oli arutusel käitumishinde asendamine kirjaliku iseloomustusega, rahvusvahelise õpilaspileti ISIC Scholar kasutuselevõtmine ja Õppurite Nõukogu uute liikmete määramine
Parts, Madli-Liis, 1969-
Jazzüritustest: rootsi jazzlauljatari Rigmor Gustafssoni kontserdist 8. dets. Estonia kontserdisaalis, inglise saksofonisti Courtney Pine heliplaadi "Resistance" esitluskontserdist 15. dets. Rock Café's, Eesti Raadio ja Jazzkaare heategevuskontserdist "Aita alustada elu" O. Ehala muusikaga, Moskva vokaalkvarteti Cool & Jazzy kontserdist, Hedvig Hansoni kontserdist "Vaikuse kaja" 1. dets. Nigulistes
19. juunil 2000 kirjutasid haridusminister Tõnis Lukas ja Briti haridus- ja tööminister Blackstone alla EV Haridusministeeriumi ja Ühendatud Kuningriigi Haridus- ja Tööministeeriumi ühisavaldusele haridus- ja koolitusalase koostöö kohta
Tallinnasse kogunesid Läänemere Agenda 21 üldhariduse töörühma liikmed kümnest riigist 22.- 23. märtsil töökoosolekule, kuulati ära läbiviidud haridusalase küsitluse tulemused ning lepiti kokku haridusalase lõppdokumendi vormistamises, mille koostamiseks peavad riigid andma ülevaate säästva arengu põhimõtete kajastumisest hariduse eesmärkides ja sisus
Ehlvest, Jaan, 1962-
Intervjuu Jaan Ehlvestiga olukorrast nii Eesti kui maailma males pärast maleolümpiat Elistas, kus Eesti meeskond jäi 40. kohale ning selle tulemusega ei olnud rahul ei meeskond ega ka Eesti Maleliit
Chaya, Etsushi; Suzuki, Tohru; Karita, Shuichi; Hanya, Akira; Yoshino-Yasuda, Shoko; Kitamoto, Noriyuki
Two protease-like proteins, KrtA and KrtC, were identified in Fusarium oxysporum 26-1. Genes coding these proteins, krtA and krtC, were isolated and characterized. Recombinant KrtA (rKrtA) and KrtC (rKrtC) were successfully expressed in Aspergillus oryzae and secreted. The combination of rKrtA and rKrtC completely removed the cuticle of wool fibers. Copyright © 2013 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.
Kaalep, Tõnu, 1966-2018
Heliplaatidest: Olav Ehala "Armastatud laulud", Rein Rannap "Tantsib klaveril", Annie "Anniemal", Freeform Five "Strangest Things", Handsome Boy Modeling School "White People", Def Räädu "Planet Duckrabbit"
Narva Peetri platsil seisnud Lenini pronksskulptuurist (skulptor Olav Männi, arhitekt Borg), mille praegune asukoht on Narva kindluse territooriumil muuseumi eksponaadina. Kommentaarid Eldar Efendijevilt
Narva Peetri platsil seisnud Lenini pronksskulptuurist (skulptor Olav Männi, arhitekt Borg), mille praegune asukoht on Narva kindluse territooriumil muuseumi eksponaadina. Kommentaarid Eldar Efendijevilt
Full Text Available Keratin subtypes are selectively expressed depending on the cell type. They not only provide structural support, but regulate the metabolic processes and signaling pathways that control the growth of the epithelium. KRT17 (keratin 17 is induced in the regenerative epithelium and acts on diverse signaling pathways. Here, we demonstrate that KRT17 is invariably and permanently induced in oral squamous cell carcinoma (OSCC, as revealed by immunohistochemistry and cDNA microarray analysis. Two representative OSCC cell lines; KRT17-weakly expressing Ca9-22 and KRT17-highly expressing HSC3 were used to establish KRT17-overexpressing Ca9-22 and KRT17-knockdown HSC3 cells. Analysis of these cells revealed that KRT17 promoted cell proliferation and migration by stimulating the Akt/mTOR pathway. KRT17 also upregulated the expression of SLC2A1 (solute carrier family 2 member 1/Glut1 and glucose uptake. To further investigate the effect of KRT17 on tumorigenesis, KRT17-knockout HSC3 cells were established and were transplanted to the cephalic skin of nude mice. The tumors that developed from KRT17-knockout HSC3 cells had a lower Ki-67 labeling index and were significantly smaller compared to the controls. These results indicate that KRT17 stimulates the Akt/mTOR pathway and glucose uptake, thereby facilitating tumor growth. We could not confirm the relationship between KRT17 and SFN (stratifin in the cells examined in this study. However, our study reinforces the concept that the cellular properties of cancer are regulated by a series of molecules similar to those found in wound healing. In OSCC, KRT17 acts as a pathogenic keratin that facilitates tumor growth through the stimulation of multiple signaling pathways, highlighting the importance of KRT17 as a multifunctional promoter of tumorigenesis.
Full Text Available Keratins are structural marker proteins with tissue specific expression; however, recent reports indicate their involvement in cancer progression. Previous study from our lab revealed deregulation of many genes related to structural molecular integrity including KRT76. Here we evaluate the role of KRT76 downregulation in oral precancer and cancer development.We evaluated KRT76 expression by qRT-PCR in normal and tumor tissues of the oral cavity. We also analyzed K76 expression by immunohistochemistry in normal, oral precancerous lesion (OPL, oral squamous cell carcinoma (OSCC and in hamster model of oral carcinogenesis. Further, functional implication of KRT76 loss was confirmed using KRT76-knockout (KO mice.We observed a strong association of reduced K76 expression with increased risk of OPL and OSCC development. The buccal epithelium of DMBA treated hamsters showed a similar trend. Oral cavity of KRT76-KO mice showed preneoplastic changes in the gingivobuccal epithelium while no pathological changes were observed in KRT76 negative tissues such as tongue.The present study demonstrates loss of KRT76 in oral carcinogenesis. The KRT76-KO mice data underlines the potential of KRT76 being an early event although this loss is not sufficient to drive the development of oral cancers. Thus, future studies to investigate the contributing role of KRT76 in light of other tumor driving events are warranted.
Full Text Available The lung alveoli slowly self-renew pneumocytes, but their facultative regeneration capacity is rapidly efficient after an injury, so fibrosis infrequently occurs. We recently observed Keratin 14 (KRT14 expression during diffuse alveolar damage (DAD, but not in controls. We wonder if KRT14 may be a marker of pneumocyte transition from quiescence to regeneration. Quantitative PCR and Western blot analyses highlighted the presence of KRT14 (mRNA and protein only in human lung samples with DAD or interstitial lung disease (ILD. In the exponentially growing cell lines A549 and H441, the mRNA and protein levels of KRT14 peaked at day one after cell seeding and decreased at day two, opposite to what observed for the proliferation marker E2F1. The inverse relation of KRT14 versus E2F1 expression holds true also for other proliferative markers, such as cyclin E1 and cyclin D1. Of interest, we also found that E2F1 silencing caused cell cycle arrest and increased KRT14 expression, whilst E2F1 stimulation induced cell cycle progression and decreased KRT14. KRT14 also increased in proliferative pneumocytes (HPAEpiC just before transdifferentiation. Overall, our results suggest that KRT14 is a viable biomarker of pneumocyte activation, and repair/regeneration. The involvement of KRT14 in regenerative process may suggest a novel pharmaceutical target to accelerate lung repair.
Chan, Carol W M; Wong, Newton A; Liu, Ying
colorectal cancer cell lines. Deletion and mutation analysis of the KRT20 promoter showed that the minimum regulatory region for the control of KRT20 expression by CDX1 is within 246 bp upstream of the KRT20 transcription start site. ChIP analysis confirmed that CDX1 binds to the predicted CDX elements...... in this region of the KRT20 promoter in vivo. In addition, immunohistochemistry showed expression of CDX1 parallels that of KRT20 in the normal crypt, which further supports their close relationship. In summary, our observations strongly imply that KRT20 is directly regulated by CDX1, and therefore suggest...... a role for CDX1 in maintaining differentiation in intestinal epithelial cells. Because a key feature of the development of a cancer is an unbalanced program of proliferation and differentiation, dysregulation of CDX1 may be an advantage for the development of a colorectal carcinoma. This could, therefore...
Stand structure and regeneration of harvested Araucaria araucana–Nothofagus stands in central Chile. Rafael M Navarro-Cerrillo, Fernando Olave, Francisco Moreno, Sergio de Miguel, Margarita Clemente ...
Amor, Mari, 1973-
Helilooja loodud originaalmuusika kasutamisest eesti sõnateatris, koostööst lavastajaga. Sõnalavastuste muusikalisest kujundusest avaldavad arvamust ka Viive Ernesaks, Ardo Ran Varres, Olav Ehala, Eino Tamberg, Mati Unt ja Rein Agur
Harvardi ülikooli tudengid plaanivad hakata välja andma ajakirja H-Bomb, mis kajastaks seksiteemat Harvardi vaatevinklist. Kommenteerivad TÜ teabejuht Illari Lään, TTÜ teabejuht Tiit Sinissaar ja Riigikogu kultuurikomisjoni esimees Olav Aarna
Laaniste, Mari, 1977-
Dokumentaalfilm animaator Priit Pärnast "Mees animatsioonist" : režissöör Hardi Volmer : peaprodutsent ja operaator Arko Okk : stsenarist Toomas Kall : helilooja Olav Ehala : Acuba Film 2005. Lisatud andmed H. Volmeri kohta
Dokumentaalfilm "Kodanik - riigi alus" : autor ja produtsent Rein Hanson : režissöörid Tambet Tasuja ja Marko Piirsoo : operaator Priit Murusalu : helilooja Olav Ehala : Läänemaa Telestuudio 2000
Narvas Peetri väljakul asunud Lenini kuju (skulptor Olav Männi, 1957) saatusest. Demonteeriti 1993. a. ja viidi Narva muuseumi territooriumile, kus ta on ainus Eestis avalikus paigas asuv Lenini kuju
Duverger, Olivier; Carlson, Jenna C; Karacz, Chelsea M; Schwartz, Mary E; Cross, Michael A; Marazita, Mary L; Shaffer, John R; Morasso, Maria I
Pachyonychia congenita (PC) is a cutaneous disorder primarily characterized by nail dystrophy and painful palmoplantar keratoderma. PC is caused by mutations in KRT6A, KRT6B, KRT6C, KRT16, and KRT17, a set of keratin genes expressed in the nail bed, palmoplantar epidermis, oral mucosal epithelium, hair follicle and sweat gland. RNA-seq analysis revealed that all PC-associated keratins (except for Krt6c that does exist in the mouse genome) are expressed in the mouse enamel organ. We further demonstrated that these keratins are produced by ameloblasts and are incorporated into mature human enamel. Using genetic and intraoral examination data from 573 adults and 449 children, we identified several missense polymorphisms in KRT6A, KRT6B and KRT6C that lead to a higher risk for dental caries. Structural analysis of teeth from a PC patient carrying a p.Asn171Lys substitution in keratin-6a (K6a) revealed disruption of enamel rod sheaths resulting in altered rod shape and distribution. Finally, this PC-associated substitution as well as more frequent caries-associated SNPs, found in two of the KRT6 genes, that result in p.Ser143Asn substitution (rs28538343 in KRT6B and rs151117600 in KRT6C), alter the assembly of K6 filaments in ameloblast-like cells. These results identify a new set of keratins involved in tooth enamel formation, distinguish novel susceptibility loci for tooth decay and reveal additional clinical features of pachyonychia congenita.
Haybaeck, Johannes; Stumptner, Cornelia; Thueringer, Andrea; Kolbe, Thomas; Magin, Thomas M; Hesse, Michael; Fickert, Peter; Tsybrovskyy, Oleksiy; Müller, Heimo; Trauner, Michael; Zatloukal, Kurt; Denk, Helmut
Keratin 8 (K8) and keratin 18 (K18) form the major hepatocyte cytoskeleton. We investigated the impact of genetic loss of either K8 or K18 on liver homeostasis under toxic stress with the hypothesis that K8 and K18 exert different functions. krt8⁻/⁻ and krt18⁻/⁻ mice crossed into the same 129-ola genetic background were treated by acute and chronic administration of 3,5-diethoxy-carbonyl-1,4-dihydrocollidine (DDC). In acutely DDC-intoxicated mice, macrovesicular steatosis was more pronounced in krt8⁻/⁻ and krt18⁻/⁻ compared with wild-type (wt) animals. Mallory-Denk bodies (MDBs) appeared in krt18⁻/⁻ mice already at an early stage of intoxication in contrast to krt8⁻/⁻ mice that did not display MDB formation when fed with DDC. Keratin-deficient mice displayed significantly lower numbers of apoptotic hepatocytes than wt animals. krt8⁻/⁻, krt18⁻/⁻ and control mice displayed comparable cell proliferation rates. Chronically DDC-intoxicated krt18⁻/⁻ and wt mice showed a similarly increased degree of steatohepatitis with hepatocyte ballooning and MDB formation. In krt8⁻/⁻ mice, steatosis was less, ballooning, and MDBs were absent. krt18⁻/⁻ mice developed MDBs whereas krt8⁻/⁻ mice on the same genetic background did not, highlighting the significance of different structural properties of keratins. They are independent of the genetic background as an intrinsic factor. By contrast, toxicity effects may depend on the genetic background. krt8⁻/⁻ and krt18⁻/⁻ mice on the same genetic background show similar sensitivity to DDC intoxication and almost resemble wt animals regarding survival, degree of porphyria, liver-to-body weight ratio, serum bilirubin and liver enzyme levels. This stands in contrast to previous work where krt8⁻/⁻ and krt18⁻/⁻ mice on different genetic backgrounds were investigated.
Full Text Available Recent studies have demonstrated that flavonoid glucuronides can be deconjugated to the active form aglycone by β-glucuronidase-expressing macrophages. Keigairengyoto (KRT is a flavonoid-rich traditional Japanese medicine reported to enhance bacterial clearance through immune modulation. Our aims are to examine the pharmacokinetics of KRT flavonoids and to identify active flavonoids contributing to the adjuvant effects of KRT. KRT was evaluated at pharmacokinetic analysis to quantify absorbed flavonoids, and cutaneous infection assay induced in mice by inoculation of Staphylococcus aureus. Preventive or therapeutic KRT administration reduced the number of bacteria in the infection site as well as macroscopic and microscopic lesion scores with efficacies similar to antibiotics. Pharmacokinetic study revealed low plasma levels of flavonoid aglycones after KRT administration; however, plasma concentrations were enhanced markedly by β-glucuronidase treatment, with baicalein the most abundant (Cmax, 1.32 µg/mL. In random screening assays, flavonoids such as bacalein, genistein, and apigenin enhanced bacteria phagocytosis by macrophages. Glucuronide bacalin was converted to aglycone baicalein by incubation with living macrophages, macrophage lysate, or skin homogenate. Taken together, the adjuvant effect of KRT may be due to some blood-absorbed flavonoids which enhance macrophage functions in host defense. Flavonoid-rich KRT may be a beneficial treatment for infectious skin inflammation.
Hirayama, Masatoshi; Liu, Ying; Kawakita, Tetsuya; Shimmura, Shigeto; Tsubota, Kazuo
The lacrimal gland secretes tear fluids that protect the ocular surface epithelium, and its dysfunction leads to dry eye disease (DED). The functional restoration of the lacrimal gland by engraftment of a bioengineered lacrimal gland using lacrimal gland germ epithelial cells has been proposed to cure DED in mice. Here, we investigate the expression profile of cytokeratins in the lacrimal gland germ epithelium to clarify their unique characteristics. We performed quantitative polymerase chain reaction (Q-PCR) and immunohistochemistry (IHC) analysis to clarify the expression profile of cytokeratin in the lacrimal gland germ epithelium. The mRNA expression of keratin (KRT) 5, KRT8, KRT14, KRT15, and KRT18 in the lacrimal gland germ epithelium was increased compared with that in mouse embryonic stem cells and the lacrimal gland germ mesenchyme, as analyzed by Q-PCR. The expression level of KRT15 increased in the transition from stem cells to lacrimal gland germ epithelium, then decreased as the lacrimal gland matured. IHC revealed that the expression set of these cytokeratins in the lacrimal gland germ epithelium was different from that in the adult lacrimal gland. The expression of KRT15 was observed in the lacrimal gland germ epithelium, and it segmentalized into some of the basal cells in the intercanulated duct in mature gland. We determined the expression profile of cytokeratins in the lacrimal gland epithelium, and identified KRT15 as a candidate unique cellular marker for the lacrimal gland germ epithelium. Copyright © 2015 Elsevier Ltd. All rights reserved.
Fischer, Heinz; Langbein, Lutz; Reichelt, Julia; Buchberger, Maria; Tschachler, Erwin; Eckhart, Leopold
K1 and K2 are the main type II keratins in the suprabasal epidermis where each of them heterodimerizes with the type I keratin K10 to form intermediate filaments. In regions of the ears, tail, and soles of the mouse, only K2 is co-expressed with K10, suggesting that these keratins suffice to form a mechanically resilient cytoskeleton. To determine the effects of the suppression of both main keratins, K2 and K10, in the suprabasal plantar epidermis of the mouse. Krt2(-/-) Krt10(-/-) mice were generated by crossing Krt2(-/-) and Krt10(-/-) mice. Epidermal morphology of soles of hind-paws was examined macroscopically and histologically. Immunofluorescence analysis and quantitative PCR analysis were performed to analyze the expression of keratins in sole skin of wildtype and Krt2(-/-) Krt10(-/-) mice. Highly abundant proteins of the sole stratum corneum were determined by electrophoretic and chromatographic separation and subsequent mass spectrometry. K2 and K10 are the most prominent suprabasal keratins in normal mouse soles with the exception of the footpads where K1, K9 and K10 predominate. Mice lacking both K2 and K10 were viable and developed epidermal acanthosis and hyperkeratosis in inter-footpad epidermis of the soles. The expression of keratins K1, K9 and K16 was massively increased at the RNA and protein levels in the soles of Krt2(-/-) Krt10(-/-) mice. This study demonstrates that the loss of the main cytoskeletal components of plantar epidermis, i.e. K2 and K10, can be only partly compensated by the upregulation of other keratins. The thickening of the epidermis in the soles of Krt2(-/-) Krt10(-/-) mice may serve as a model for pathomechanistic aspects of palmoplantar keratoderma. Copyright © 2015. Published by Elsevier Ireland Ltd.
Rodrigues-Pinto, Ricardo; Berry, Andrew; Piper-Hanley, Karen; Hanley, Neil; Richardson, Stephen M; Hoyland, Judith A
In humans, the nucleus pulposus (NP) is composed of large vacuolated notochordal cells in the fetus but, soon after birth, becomes populated by smaller, chondrocyte-like cells. Although animal studies indicate that notochord-derived cells persist in the adult NP, the ontogeny of the adult human NP cell population is still unclear. As such, identification of unique notochordal markers is required. This study was conducted to determine the spatiotemporal expression of putative human notochordal markers to aid in the elucidation of the ontogeny of adult human NP cells. Human embryos and fetuses (3.5-18 weeks post-conception (WPC)) were microdissected to isolate the spine anlagens (notochord and somites/sclerotome). Morphology of the developing IVD was assessed using hematoxylin and eosin. Expression of keratin (KRT) 8, KRT18, KRT19, CD24, GAL3, CD55, BASP1, CTGF, T, CD90, Tie2, and E-cadherin was assessed using immunohistochemistry. KRT8, KRT18, KRT19 were uniquely expressed by notochordal cells at all spine levels at all stages studied; CD24 was expressed at all stages except 3.5 WPC. While GAL3, CD55, BASP1, CTGF, and T were expressed by notochordal cells at specific stages, they were also co-expressed by sclerotomal cells. CD90, Tie2, and E-cadherin expression was not detectable in developing human spine cells at any stage. This study has identified, for the first time, the consistent expression of KRT8, KRT18, KRT19, and CD24 as human notochord-specific markers during early IVD development. Thus, we propose that these markers can be used to help ascertain the ontogeny of adult human NP cells. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. J Orthop Res 34:1327-1340, 2016. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc.
Rodrigues‐Pinto, Ricardo; Berry, Andrew; Piper‐Hanley, Karen; Hanley, Neil; Richardson, Stephen M.
ABSTRACT In humans, the nucleus pulposus (NP) is composed of large vacuolated notochordal cells in the fetus but, soon after birth, becomes populated by smaller, chondrocyte‐like cells. Although animal studies indicate that notochord‐derived cells persist in the adult NP, the ontogeny of the adult human NP cell population is still unclear. As such, identification of unique notochordal markers is required. This study was conducted to determine the spatiotemporal expression of putative human notochordal markers to aid in the elucidation of the ontogeny of adult human NP cells. Human embryos and fetuses (3.5–18 weeks post‐conception (WPC)) were microdissected to isolate the spine anlagens (notochord and somites/sclerotome). Morphology of the developing IVD was assessed using hematoxylin and eosin. Expression of keratin (KRT) 8, KRT18, KRT19, CD24, GAL3, CD55, BASP1, CTGF, T, CD90, Tie2, and E‐cadherin was assessed using immunohistochemistry. KRT8, KRT18, KRT19 were uniquely expressed by notochordal cells at all spine levels at all stages studied; CD24 was expressed at all stages except 3.5 WPC. While GAL3, CD55, BASP1, CTGF, and T were expressed by notochordal cells at specific stages, they were also co‐expressed by sclerotomal cells. CD90, Tie2, and E‐cadherin expression was not detectable in developing human spine cells at any stage. This study has identified, for the first time, the consistent expression of KRT8, KRT18, KRT19, and CD24 as human notochord‐specific markers during early IVD development. Thus, we propose that these markers can be used to help ascertain the ontogeny of adult human NP cells. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. J Orthop Res 34:1327–1340, 2016. PMID:26910849
... can be triggered by UV light, sweating, or friction on the skin. The pigmentation changes characteristic of ... A, Ruzicka T, Betz RC, Hanneken S. The First Report of KRT5 Mutation Underlying Acantholytic Dowling-Degos Disease ...
Sankar, Savita; Tanner, Jason M.; Bell, Russell; Chaturvedi, Aashi; Randall, R. Lor; Beckerle, Mary C.
Oncogenic transformation in Ewing sarcoma is caused by EWS/FLI, an aberrant transcription factor fusion oncogene. Glioma-associated oncogene homolog 1 (GLI1) is a critical target gene activated by EWS/FLI, but the mechanism by which GLI1 contributes to the transformed phenotype of Ewing sarcoma was unknown. In this work, we identify keratin 17 (KRT17) as a direct downstream target gene upregulated by GLI1. We demonstrate that KRT17 regulates cellular adhesion by activating AKT/PKB (protein kinase B) signaling. In addition, KRT17 is necessary for oncogenic transformation in Ewing sarcoma and accounts for much of the GLI1-mediated transformation function but via a mechanism independent of AKT signaling. Taken together, our data reveal previously unknown molecular functions for a cytoplasmic intermediate filament protein, KRT17, in coordinating EWS/FLI- and GLI1-mediated oncogenic transformation and cellular adhesion in Ewing sarcoma. PMID:24043308
Uuest heliplaadist "Grieg: Works for String Orchestra. Gothenburg Symphony Orchestra, Neeme Järvi. CD 437 520 - 2GH Grieg: Land Sighting, Op.32, Olav Trygvason, Op.50, Per Gynt Suites N1,Op.46, N2,Op.55. Randi Stene, Anne Gjevang, Hakan Hagegard, Gothenburg Symphony Chorus, Gothenburg Symphony Orchestra, Neeme Järvi. CD 437 523 - 2 GH
Karits, Christel, 1966-
Muusikaturu korraldamisest 18. sept. Estonia teatrihoone taga ajaloolisel turuplatsil. Katri Kaasik-Aaslavi ja Vaino Vahingu näidendi "Teatriromanss" (muusika arranzheerija ja pianist Olav Ehala) esietendusest Estonia kammersaalis 22. oktoobril. Giuseppe Verdi ooperi "Aida" etendamisest Rocca al Mare Onistar Tennisekeskuses 8.-10., 12.-17. oktoobril
Galeriis SED ARTE avati 6. mail rahvusvaheline kunstinäitus "XXI sajandi natüürmort". Eksponeeritud on 47 kunstniku tööd Eestist, USA-st, Valgevenest, Ukrainast ja Venemaalt. Eestist osalevad Nikolai Kormašov, Olav Maran, Tauno Kangro, Slava Semerikov, Vladimir Anšon, Sergei Inkatov, Sergei Minin ja teised
Tungal, Leelo, 1947-
Joonisfilmid "Lotte" ja "Lotte reis lõunamaale" : stsenaristid Andrus Kivirähk, Janno Põldma, Heiki Ernits : kunstnik Heiki Ernits : lavastajad Leo Lätti, Ebe Tramberg : helilooja Olav Ehala : Eesti Joonisfilm 2000. Lisa : S. Teinemaa koostatud J. Põldma ja H. Ernitsa filmograafia
Riigikogu liige Jaak Allik peab vajalikuks leida ETV-le lisamiljoneid olümpiamängude ja jalgpalli MM-i teleülekanneteks. Riigikogu liikmed Olav Aarna ja Katrin Saks kritiseerisid valitsust, et rahvusringhäälingu arengukava suhtes pole võetud seisukohta. Kultuuriminister Raivo Palmaru arvamusi. Lisa: Ringhäälingureform tulekul
Sõrra, Jaan, 1954-
Konverentsi "580 päeva Euroopa Liidus " osalejate pöördumine. Vt ka vastused deklaratsioonile lk. 103-107 riigisekretär Heiki Loot, põllumajandusminister Ester Tuiksoo, haridus- ja teadusminister Mailis Reps, keskkonnaminister Villu Reiljan, Riigikogu kultuurikomisjon Olav Aarna, rahandusminister Aivar Sõerd ja Aare Järvan
Myklebust, Jon Olav
This article, by Jon Olav Myklebust from Volda University, Norway, presents analyses of social security dependence among students with special educational needs in Norway who at the start of upper secondary school had various disabilities--of a somatic, psychological and/or social nature. They were all educated in ordinary schools, in special or…
Tamm, Saari, 1968-
Lühisõnumid: ERSO osales Läänemere festivalil. 18. - 29. VIII toimuvad EMAs suvekursused "Crossing Borders in interpretation of Classical Music and jazz". Konstantin Türnpu 140. 22. - 24. VIII toimub XII Lõuna-Eesti noorte pianistide suvekool. 21. VIII esineb Estonia kontserdisaalis Helsinki Festival Orchestra. 20. VIII toimub Tartu laululaval Olav Ehala loomingu galakontsert
Ma, Yan-Min; Wu, Kai-Jie; Dang, Qiang; Shi, Qi; Gao, Yang; Guo, Peng; Xu, Shan; Wang, Xin-Yang; He, Da-Lin; Gong, Yong-Guang
Androgen therapy is the mainstay of treatment for the hypogonadotropic hypogonadal micropenis because it obviously enhances penis growth in prepubescent microphallic patients. However, the molecular mechanisms of androgen treatment leading to penis growth are still largely unknown. To clarify this well-known phenomenon, we successfully generated a castrated male Sprague Dawley rat model at puberty followed by testosterone administration. Interestingly, compared with the control group, testosterone treatment stimulated a dose-dependent increase of penis weight, length, and width in castrated rats accompanied with a dramatic recovery of the pathological changes of the penis. Mechanistically, testosterone administration substantially increased the expression of androgen receptor (AR) protein. Increased AR protein in the penis could subsequently initiate transcription of its target genes, including keratin 33B (Krt33b). Importantly, we demonstrated that KRT33B is generally expressed in the rat penis and that most KRT33B expression is cytoplasmic. Furthermore, AR could directly modulate its expression by binding to a putative androgen response element sequence of the Krt33b promoter. Overall, this study reveals a novel mechanism facilitating penis growth after testosterone treatment in precastrated prepubescent animals, in which androgen enhances the expression of AR protein as well as its target genes, such as Krt33b.
Full Text Available Androgen therapy is the mainstay of treatment for the hypogonadotropic hypogonadal micropenis because it obviously enhances penis growth in prepubescent microphallic patients. However, the molecular mechanisms of androgen treatment leading to penis growth are still largely unknown. To clarify this well-known phenomenon, we successfully generated a castrated male Sprague Dawley rat model at puberty followed by testosterone administration. Interestingly, compared with the control group, testosterone treatment stimulated a dose-dependent increase of penis weight, length, and width in castrated rats accompanied with a dramatic recovery of the pathological changes of the penis. Mechanistically, testosterone administration substantially increased the expression of androgen receptor (AR protein. Increased AR protein in the penis could subsequently initiate transcription of its target genes, including keratin 33B (Krt33b. Importantly, we demonstrated that KRT33B is generally expressed in the rat penis and that most KRT33B expression is cytoplasmic. Furthermore, AR could directly modulate its expression by binding to a putative androgen response element sequence of the Krt33b promoter. Overall, this study reveals a novel mechanism facilitating penis growth after testosterone treatment in precastrated prepubescent animals, in which androgen enhances the expression of AR protein as well as its target genes, such as Krt33b.
Full Text Available A validated animal model would assist with research on the immunological consequences of the chronic expression of stress keratins KRT6, KRT16, and KRT17, as observed in human pre-malignant hyperproliferative epithelium. Here we examine keratin gene expression profile in skin from mice expressing the E7 oncoprotein of HPV16 (K14E7 demonstrating persistently hyperproliferative epithelium, in nontransgenic mouse skin, and in hyperproliferative actinic keratosis lesions from human skin. We demonstrate that K14E7 mouse skin overexpresses stress keratins in a similar manner to human actinic keratoses, that overexpression is a consequence of epithelial hyperproliferation induced by E7, and that overexpression further increases in response to injury. As stress keratins modify local immunity and epithelial cell function and differentiation, the K14E7 mouse model should permit study of how continued overexpression of stress keratins impacts on epithelial tumor development and on local innate and adaptive immunity.
Full Text Available During the 30th, 31st, and 32nd Japanese Antarctic Research Expeditions (JARE-30,JARE-31,and JARE-32, sea-ice conditions were recorded by video camera on board the SHIRASE. Then, the sea-ice images were used to estimate compactness and thickness quantitatively. Analyzed legs are those toward Breid Bay and from Breid Bay to Syowa Station during JARE-30 and JARE-31,and those toward the Prince Olav Coast, from the Prince Olav Coast to Breid Bay, and from Breid Bay to Syowa Station during JARE-32. The results show yearly variations of ice compactness and thickness, latitudinal variations of thickness, and differences in thickness histograms between JARE-30 and JARE-32 in Lutzow-Holm Bay. Albedo values were measured simultaneously by a shortwave radiometer. These values are proportional to those of ice compactness. Finally, we examined the relationship between ice compactness and vertical gradient of air temperature above sea ice.
Stermer, E.M. [Univ. of Oslo, Dept. of Oral Radiology, Oslo (Norway); Risnes, S. [Univ. of Oslo, Dept. of Oral Biology, Faculty of Dentistry, Oslo (Norway); Fischer, P.M. [Chalmers Univ. of Technology, Dept. of Physics, SIMS Lab., Goeteborg (Sweden)
A blackish staining found on the crowns of teeth of 51 skulls from the excavation of the medieval St. Olav`s church in Trondheim was analyzed using secondary ion mass spectrometry (SIMS) and atomic absorption spectrometry (AAS). In four teeth, mass spectra and step scan concentration profiles of SIMS were performed and compared with the grey scale pattern in photographs of the analyzed paths. The manganese curve showed the highest degree of conformity with the grey scale pattern. The AAS analysis confirmed the increased content of manganese in blackish stained enamel. It was concluded that manganese, probably in the form of an oxide deposited from the soil, was the cause of the blackish staining. (au).
Stermer Beyer-Olsen, E M
An excavation of a part of the graveyard of St Olav's church, Trondheim, Norway, uncovered 389 tombs from the medieval period (1100-1600). Radiographic examination of 140 skulls with an intact premaxilla revealed hyperdontia in the form of a mesiodens in two (1.4%) cases. This is within the same range as similar medieval and present Nordic populations. Change in functional pattern does not seem to influence the prevalence.
The 38 staff members who are celebrating 25 years at CERN in 2010 were invited by the Director-General to a reception in their honour on 21 October. ASBURY David IT HEGARTY Seamus HR BAUDRENGHIEN Philippe BE ISNARD Christian IT BERGSMA Felix PH JONES Robert IT BERNAL Jean-Manuel TE JOUBERJEAN Franck IT BERRIG Olav Ejner BE LAGRANGE Thierry FP BONT Hillebrand GS MARIN Antonio BE BOURGEOIS Nicolas PH MESENGE Pascal EN BOURREL Thierry EN MISSIAEN Dominique BE ...
Greenwold, Matthew J.; Bao, Weier; Jarvis, Erich D.
BACKGROUND: Vertebrate skin appendages are constructed of keratins produced by multigene families. Alpha (α) keratins are found in all vertebrates, while beta (β) keratins are found exclusively in reptiles and birds. We have studied the molecular evolution of these gene families in the genomes...... of 48 phylogenetically diverse birds and their expression in the scales and feathers of the chicken. RESULTS: We found that the total number of α-keratins is lower in birds than mammals and non-avian reptiles, yet two α-keratin genes (KRT42 and KRT75) have expanded in birds. The β-keratins, however...
Full Text Available Recent discovery of hair follicle keratin 75 (KRT75 in enamel raises questions about the function of this protein in enamel and the mechanisms of its secretion. It is also not clear how this protein with a very specific and narrow expression pattern, limited to the inner root sheath of the hair follicle, became associated with enamel. We propose a hypothesis that KRT75 was co-opted by ameloblasts during the evolution of Tomes' process and the prismatic enamel in synapsids.
Starostová, Michaela; Čermák, Vladimír; Dvořáková, Marta; Karafiát, Vít; Kosla, Jan; Dvořák, Michal
Roč. 540, č. 1 (2014), s. 122-129 ISSN 0378-1119 R&D Projects: GA AV ČR KAN200520801 Institutional support: RVO:68378050 Keywords : Melanocyte development * Tamoxifen-inducible v-Myb * v-Myb-dependent genes * PRDC * KRT19 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.138, year: 2014
Basmanav, F Buket; Oprisoreanu, Ana-Maria; Pasternack, Sandra M
Dowling-Degos disease (DDD) is an autosomal-dominant genodermatosis characterized by progressive and disfiguring reticulate hyperpigmentation. We previously identified loss-of-function mutations in KRT5 but were only able to detect pathogenic mutations in fewer than half of our subjects. To ident...
Koolmar, Roman, 1904-1971
1937. a. projekteeritud Teedeministeeriumi ametnike korteriühing "Ühiskodu" ja kohtunike korteriühing "Asum" Raua põik 3 ja 5. Välisvaade tänavalt ja sisehoovist. Korruse plaanid. Lk. 65 "Ühiskodu" I korrusel, krt. 2 elanud Koolmarite korteri kaminanurk
Agbatogun, Alaba Olaoluwakotansibe
Drawing from the socio-cultural theory of Vygotsky, this study compared the academic performance gains scores of pupils in a Keypad Response Technology (KRT) class with those in two other pedagogies to determine the learners' language proficiency level in ESL classroom. A sample of 99 Nigerian primary six pupils participated in the study.…
Full Text Available BACKGROUND: Application of induced pluripotent stem (iPS cells in regenerative medicine will bypass ethical issues associated with use of embryonic stem cells. In addition, patient-specific IPS cells can be useful to elucidate the pathophysiology of genetic disorders, drug screening, and tailor-made medicine. However, in order to apply iPS cells to mitotic tissue, induction of tissue stem cells that give rise to progeny of the target organ is required. METHODOLOGY/PRINCIPAL FINDINGS: We induced stratified epithelial cells from mouse iPS cells by co-culture with PA6 feeder cells (SDIA-method with use of BMP4. Clusters of cells positive for the differentiation markers KRT1 or KRT12 were observed in KRT14-positive colonies. We successfully cloned KRT14 and p63 double-positive stratified epithelial progenitor cells from iPS-derived epithelial cells, which formed stratified epithelial sheets consisting of five- to six-polarized epithelial cells in vitro. When these clonal cells were cultured on denuded mouse corneas, a robust stratified epithelial layer was observed with physiological cell polarity including high levels of E-cadherin, p63 and K15 expression in the basal layer and ZO-1 in the superficial layer, recapitulating the apico-basal polarity of the epithelium in vivo. CONCLUSIONS/SIGNIFICANCE: These results suggest that KRT14 and p63 double-positive epithelial progenitor cells can be cloned from iPS cells in order to produce polarized multilayer epithelial cell sheets.
Carén, Helena; Djos, Anna; Nethander, Maria; Sjöberg, Rose-Marie; Kogner, Per; Enström, Camilla; Nilsson, Staffan; Martinsson, Tommy
Epigenetic mechanisms such as DNA methylation and histone modifications are important regulators of gene expression and are frequently involved in silencing tumor suppressor genes. In order to identify genes that are epigenetically regulated in neuroblastoma tumors, we treated four neuroblastoma cell lines with the demethylating agent 5-Aza-2'-deoxycytidine (5-Aza-dC) either separately or in conjunction with the histone deacetylase inhibitor trichostatin A (TSA). Expression was analyzed using whole-genome expression arrays to identify genes activated by the treatment. These data were then combined with data from genome-wide DNA methylation arrays to identify candidate genes silenced in neuroblastoma due to DNA methylation. We present eight genes (KRT19, PRKCDBP, SCNN1A, POU2F2, TGFBI, COL1A2, DHRS3 and DUSP23) that are methylated in neuroblastoma, most of them not previously reported as such, some of which also distinguish between biological subsets of neuroblastoma tumors. Differential methylation was observed for the genes SCNN1A (p < 0.001), PRKCDBP (p < 0.001) and KRT19 (p < 0.01). Among these, the mRNA expression of KRT19 and PRKCDBP was significantly lower in patients that have died from the disease compared with patients with no evidence of disease (fold change -8.3, p = 0.01 for KRT19 and fold change -2.4, p = 0.04 for PRKCDBP). In our study, a low methylation frequency of SCNN1A, PRKCDBP and KRT19 is significantly associated with favorable outcome in neuroblastoma. It is likely that analysis of specific DNA methylation will be one of several methods in future patient therapy stratification protocols for treatment of childhood neuroblastomas
Liffers, Sven-T; Schwarte-Waldhoff, Irmgard; Meyer, Helmut E; Stühler, Kai; Hahn, Stephan A; Maghnouj, Abdelouahid; Munding, Johanna B; Jackstadt, René; Herbrand, Ulrike; Schulenborg, Thomas; Marcus, Katrin; Klein-Scory, Susanne; Schmiegel, Wolff
Inactivating mutations of SMAD4 are frequent in metastatic colorectal carcinomas. In previous analyses, we were able to show that restoration of Smad4 expression in Smad4-deficient SW480 human colon carcinoma cells was adequate to suppress tumorigenicity and invasive potential, whereas in vitro cell growth was not affected. Using this cellular model system, we searched for new Smad4 targets comparing nuclear subproteomes derived from Smad4 re-expressing and Smad4 negative SW480 cells. High resolution two-dimensional (2D) gel electrophoresis was applied to identify novel Smad4 targets in the nuclear subproteome of Smad4 re-expressing SW480 cells. The identified candidate protein Keratin 23 was further characterized by tandem affinity purification. Immunoprecipitation, subfractionation and immunolocalization studies in combination with RNAi were used to validate the Keratin 23-14-3-3ε interaction. We identified keratins 8 and 18, heat shock proteins 60 and 70, plectin 1, as well as 14-3-3ε and γ as novel proteins present in the KRT23-interacting complex. Co-immunoprecipitation and subfractionation analyses as well as immunolocalization studies in our Smad4-SW480 model cells provided further evidence that KRT23 associates with 14-3-3ε and that Smad4 dependent KRT23 up-regulation induces a shift of the 14-3-3ε protein from a nuclear to a cytoplasmic localization. Based on our findings we propose a new regulatory circuitry involving Smad4 dependent up-regulation of KRT23 (directly or indirectly) which in turn modulates the interaction between KRT23 and 14-3-3ε leading to a cytoplasmic sequestration of 14-3-3ε. This cytoplasmic KRT23-14-3-3 interaction may alter the functional status of the well described 14-3-3 scaffold protein, known to regulate key cellular processes, such as signal transduction, cell cycle control, and apoptosis and may thus be a previously unappreciated facet of the Smad4 tumor suppressive circuitry
Bosna, Valeria Vittoria Aurora
El Escultismo para chicos empezó en Inglaterra en 1907 por Robert Baden Powell y en 1910 antes con Agnes Baden Powell y después con Olave Sant Claire Soames iniciaron el Escultismo femenino y el Guidismo. El Movimiento educativo scout para chicos y chicas es la organización juvenil más difundida al mundo. En Italia el Escultismo masculino y femenino llegó en el 1912 y durante todo el siglo XX trabajó con chicos y chicas de manera separada hasta al 1976. Durante los años cincuenta y sesenta, g...
Vanemuise kontserdimajas 11. nov. isadepäeva kontserdil "Isad ja pojad" esinemas Olav Ehala ja Tanel Ehala klaveril ja Pärnu Linnaorkester, kaastegev Kiigelaulukuuik (dirigent Erki Pehk). 12. nov. kammerlaval festivalil "Fiesta de la guitarra '05" kitarriduo Katona Twins, 17. nov. Aleksander Rudini ja Tallinna Kammerorkestri kontsert. TÜ aulas 11. nov. kitarrikontsert: Rody van Gemert & Mikko Ikäheimo, 13. nov. "Fiesta de la guitarra '05" pidulik gala. TÜ ajaloo muuseumis 14. nov. Elleri Muusikakooli kontsert "Sügisbarokk". Jaani kirikus 13. nov. festivalil "Fiesta de la guitarra '05" Miguel Rivera ja Luis Carro Barquero
Full Text Available A 50-year-old man presented with congenital scaling and hyperkeratosis on his palms, the soles of his feet and the extensor areas of his joints. The flexural areas were unaffected. His maternal grandmother, questionably his maternal uncle, his mother, all three brothers, one of his two sisters as well as two nephews and three nieces have or had similar skin changes. A punch biopsy was taken from the left palm. Clinical and histological signs led to the diagnosis of erythrodermia congenitalis ichthyosiformis bullosa of Brocq. We confirmed this genetically and found a heterozygous duplication (c.1752dupT in the keratin 1 gene (KRT-1. To our knowledge, this is the first case of this skin condition reported in the literature with a heterozygous duplication (c.1752dupT in KRT-1.
Vestentoft, Peter Siig; Jelnes, Peter; Andersen, Jesper Bøje
differentially up- or down-modulated (P tier of defense (Agrn, Bgn, Fbn1, Col4a1, Col8a1, Col9a3, Lama5, Lamb1, Lamb2, Itga4, Igtb2, Itgb4, Itgb6, Nid2), and their signal intensities showed a strong or very...... strong correlation with Krt1- 19, a well-established marker of a ductular/HPC reaction. Furthermore, a significant up-modulation and very strong correlation between the transcriptional profiles of Krt1-19 and St14 encoding matriptase, a component of a novel protease system, was found in the second tier...... that laminin, Collagen1a1, agrin and nidogen1 surrounded bile ducts, proliferating cholangiocytes, and HPCs in ductular reactions regardless of the nature of defense. Similarly, matriptase and HAI-1 were expressed in cholangiocytes regardless of the tier of defense, but in the second tier of defense...
Rasha R. Ahmed
Full Text Available BACKGROUND: Impaired wound healing is a complication of diabetes and a serious problem in clinical practice. We previously found that whey protein (WP was able to regulate wound healing normally in streptozotocin (STZ-dia-betic models. This subsequent study was designed to assess the effect of WP on heat shock protein-72 (Hsp72 and keratin16 (Krt16 expression during wound healing in diabetic rats. METHODS: WP at a dosage of 100 mg/kg of body weight was orally administered daily to wounded normal and STZ-diabetic rats for 8 days. RESULTS: At day 4, the WP-treated diabetic wound was significantly reduced compared to that in the corresponding control. Diabetic wounded rats developed severe inflammatory infiltration and moderate capillary dilatation and regeneration. Treated rats had mild necrotic formation, moderate infiltration, moderate to severe capillary dilatation and regeneration, in addition to moderate epidermal formation. Hsp72 and Krt16 densities showed low and dense activity in diabetic wounded and diabetic wounded treated groups, respectively. At day 8, WP-treatment of diabetic wounded animals revealed great amelioration with complete recovery and closure of the wound. Reactivity of Hsp72 and Krt16 was reversed, showing dense and low, or medium and low, activity in the diabetic wounded and diabetic wounded treated groups, respectively. Hsp72 expression in the pancreas was found to show dense reactivity with WP-treated diabetic wound rats. CONCLUSION: This data provides evidence for the potential impact of WP in the up-regulation of Hsp72 and Krt16 in T1D, resulting in an improved wound healing process in diabetic models.
Hu, Wen-Yang; Hu, Dan-Ping; Xie, Lishi; Li, Ye; Majumdar, Shyama; Nonn, Larisa; Hu, Hong; Shioda, Toshi; Prins, Gail S
Using primary cultures of normal human prostate epithelial cells, we developed a novel prostasphere-based, label-retention assay that permits identification and isolation of stem cells at a single cell level. Their bona fide stem cell nature was corroborated using in vitro and in vivo regenerative assays and documentation of symmetric/asymmetric division. Robust WNT10B and KRT13 levels without E-cadherin or KRT14 staining distinguished individual stem cells from daughter progenitors in spheroids. Following FACS to isolate label-retaining stem cells from label-free progenitors, RNA-seq identified unique gene signatures for the separate populations which may serve as useful biomarkers. Knockdown of KRT13 or PRAC1 reduced sphere formation and symmetric self-renewal highlighting their role in stem cell maintenance. Pathways analysis identified ribosome biogenesis and membrane estrogen-receptor signaling enriched in stem cells with NF-ĸB signaling enriched in progenitors; activities that were biologically confirmed. Further, bioassays identified heightened autophagy flux and reduced metabolism in stem cells relative to progenitors. These approaches similarly identified stem-like cells from prostate cancer specimens and prostate, breast and colon cancer cell lines suggesting wide applicability. Together, the present studies isolate and identify unique characteristics of normal human prostate stem cells and uncover processes that maintain stem cell homeostasis in the prostate gland. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
Full Text Available Using primary cultures of normal human prostate epithelial cells, we developed a novel prostasphere-based, label-retention assay that permits identification and isolation of stem cells at a single cell level. Their bona fide stem cell nature was corroborated using in vitro and in vivo regenerative assays and documentation of symmetric/asymmetric division. Robust WNT10B and KRT13 levels without E-cadherin or KRT14 staining distinguished individual stem cells from daughter progenitors in spheroids. Following FACS to isolate label-retaining stem cells from label-free progenitors, RNA-seq identified unique gene signatures for the separate populations which may serve as useful biomarkers. Knockdown of KRT13 or PRAC1 reduced sphere formation and symmetric self-renewal highlighting their role in stem cell maintenance. Pathways analysis identified ribosome biogenesis and membrane estrogen-receptor signaling enriched in stem cells with NF-ĸB signaling enriched in progenitors; activities that were biologically confirmed. Further, bioassays identified heightened autophagy flux and reduced metabolism in stem cells relative to progenitors. These approaches similarly identified stem-like cells from prostate cancer specimens and prostate, breast and colon cancer cell lines suggesting wide applicability. Together, the present studies isolate and identify unique characteristics of normal human prostate stem cells and uncover processes that maintain stem cell homeostasis in the prostate gland.
Full Text Available Although recent cancer genomics studies have identified a large number of genes that were mutated in human cancers, p53 remains as the most frequently mutated gene. To further elucidate the p53-signalling network, we performed transcriptome analysis on 24 tissues in p53+/+ or p53−/− mice after whole-body X-ray irradiation. Here we found transactivation of a total of 3551 genes in one or more of the 24 tissues only in p53+/+ mice, while 2576 genes were downregulated. p53 mRNA expression level in each tissue was significantly associated with the number of genes upregulated by irradiation. Annotation using TCGA (The Cancer Genome Atlas database revealed that p53 negatively regulated mRNA expression of several cancer therapeutic targets or pathways such as BTK, SYK, and CTLA4 in breast cancer tissues. In addition, stomach exhibited the induction of Krt6, Krt16, and Krt17 as well as loricrin, an epidermal differentiation marker, after the X-ray irradiation only in p53+/+ mice, implying a mechanism to protect damaged tissues by rapid induction of differentiation. Our comprehensive transcriptome analysis elucidated tissue specific roles of p53 and its signalling networks in DNA-damage response that will enhance our understanding of cancer biology.
Omlor, G W; Nerlich, A G; Tirlapur, U K; Urban, J P; Guehring, T
Embryonic notochordal disc nucleus cells (NC) have been identified to protect disc tissue against disc degeneration but in human beings NC phenotype gets lost with aging and the pathophysiological mechanisms are poorly understood. NC may stimulate other cells via soluble factors, and NC-conditioned medium can be used to stimulate matrix production of other disc cells and mesenchymal stem cells and thus may be of special interest for biological disc repair. As this stimulatory effect is associated with the NC phenotype, we investigated how cell morphology and gene-expression of the NC phenotype changes with time in 3D-cell culture. NC and inner annulus chondrocyte-like cells (CLC) from immature pigtails (freshly isolated cells/tissue, 3D-alginate beads, 3D-clusters) were cultured for up to 16 days under normoxia and hypoxia. Protein-expression was analysed by immunohistology and gene-expression analysis was carried out on freshly isolated cells and cultured cells. Cell morphology and proliferation were analysed by two-photon-laser-microscopy. Two-photon-laser-microscopy showed a homogenous and small CLC population in the inner annulus, which differed from the large vacuole-containing NC in the nucleus. Immunohistology found 93 % KRT8 positive cells in the nucleus and intracellular and pericellular Col2, IL6, and IL12 staining while CLC were KRT8 negative. Freshly isolated NC showed significantly higher KRT8 and CAIII but lower Col2 gene-expression than CLC. NC in 3D-cultures demonstrated significant size reduction and loss of vacuoles with culture time, all indicating a loss of the characteristic NC morphology. Hypoxia reduced the rate of decrease in NC size and vacuoles. Gene-expression of KRT8 and CAIII in NC fell significantly early in culture while Col2 did not decrease significantly within the culture period. In CLC, KRT8 and CAIII gene-expression was low and did not change noticeably in culture, whereas Col2 expression fell with time in culture. 3D
Full Text Available BACKGROUND: Obesity is a complex, multifactorial disorder influenced by the interaction of genetic, epigenetic, and environmental factors. Obesity increases the risk of contracting many chronic diseases or metabolic syndrome. Researchers have established several mammalian models of obesity to study its underlying mechanism. However, a lower vertebrate model for conveniently performing drug screening against obesity remains elusive. The specific aim of this study was to create a zebrafish obesity model by over expressing the insulin signaling hub of the Akt1 gene. METHODOLOGY/PRINCIPAL FINDINGS: Skin oncogenic transformation screening shows that a stable zebrafish transgenic of Tg(krt4Hsa.myrAkt1(cy18 displays severely obese phenotypes at the adult stage. In Tg(krt4:Hsa.myrAkt1(cy18, the expression of exogenous human constitutively active Akt1 (myrAkt1 can activate endogenous downstream targets of mTOR, GSK-3α/β, and 70S6K. During the embryonic to larval transitory phase, the specific over expression of myrAkt1 in skin can promote hypertrophic and hyperplastic growth. From 21 hour post-fertilization (hpf onwards, myrAkt1 transgene was ectopically expressed in several mesenchymal derived tissues. This may be the result of the integration position effect. Tg(krt4:Hsa.myrAkt1(cy18 caused a rapid increase of body weight, hyperplastic growth of adipocytes, abnormal accumulation of fat tissues, and blood glucose intolerance at the adult stage. Real-time RT-PCR analysis showed the majority of key genes on regulating adipogenesis, adipocytokine, and inflammation are highly upregulated in Tg(krt4:Hsa.myrAkt1(cy18. In contrast, the myogenesis- and skeletogenesis-related gene transcripts are significantly downregulated in Tg(krt4:Hsa.myrAkt1(cy18, suggesting that excess adipocyte differentiation occurs at the expense of other mesenchymal derived tissues. CONCLUSION/SIGNIFICANCE: Collectively, the findings of this study provide direct evidence that Akt1
Rita Marie Sandberg
Full Text Available Objective. To study health-related quality of life (HRQoL in obese presurgery patients with binge eating disorder (BED and with subdiagnostic binge eating disorder (SBED compared to patients without eating disorders or SBED. Method. Participants were patients referred to St. Olavs University Hospital, Norway, for bariatric surgery. Eating Disorders in Obesity (EDO questionnaire was used to diagnose BED and SBED. Short-Form Health Survey (SF-12 assessed health-related quality of life. Questionnaires were returned by 160 of 209 patients. The present study sample consisted of 143 patients (103 women and 40 men as 17 patients did not complete the SF-12. Results. Patients with BED and patients with SBED both had significantly lower mental HRQoL, but not physical HRQoL, compared to patients without eating disorders. Discussion. The findings indicate that obese presurgery patients with BED, and also SBED, may have special treatment needs in regard to their mental health.
Dr. Cameron joined the Arctic Institute of North America in 1956 to participate in IGY-related activities in Antarctica. He served as Chief Glaciologist at Wilkes Station, on the coast of East Antarctica. This was a joint Navy-civilian operation consisting of 17 Navy personnel and 10 scientists. Specifically, his glaciological team consisted of two colleagues with whom he had worked before - Olav Loken in Norway in the summer of 1953, and John Molholm in Greenland in the summer of 1954. This team spent much of its time at a remote station established 80 kilometers (50 miles) inland, where they conducted both meteorological and glaciological studies. One of the glaciological studies entailed digging a 35-meter (approx.115-foot) vertical pit to study snow densification and stratigraphy. The assignment for the Navy Seabees was to first establish a joint US-NZ base at Cape Hallett and then go along the coast of East Antarctica and set up Wilkes Station.
Stermer, E.M.; Risnes, S.; Fischer, P.M.
A blackish staining found on the crowns of teeth of 51 skulls from the excavation of the medieval St. Olav's church in Trondheim was analyzed using secondary ion mass spectrometry (SIMS) and atomic absorption spectrometry (AAS). In four teeth, mass spectra and step scan concentration profiles of SIMS were performed and compared with the grey scale pattern in photographs of the analyzed paths. The manganese curve showed the highest degree of conformity with the grey scale pattern. The AAS analysis confirmed the increased content of manganese in blackish stained enamel. It was concluded that manganese, probably in the form of an oxide deposited from the soil, was the cause of the blackish staining. (au)
Full Text Available Apart from the well-known role of somatic cell count as a parameter reflecting the inflammatory status of the mammary gland, the composition of cells isolated from milk is considered as a valuable material for gene expression studies in mammals. Due to its unique composition, in recent years an increasing interest in mare's milk consumption has been observed. Thus, investigating the genetic background of horse's milk variability presents and interesting study model. Relying on 39 milk samples collected from mares representing three breeds (Polish Primitive Horse, Polish Cold-blooded Horse, Polish Warmblood Horse we aimed to investigate the utility of equine milk somatic cells as a source of mRNA and to screen the best reference genes for RT-qPCR using geNorm and NormFinder algorithms. The results showed that despite relatively low somatic cell counts in mare's milk, the amount and the quality of the extracted RNA are sufficient for gene expression studies. The analysis of the utility of 7 potential reference genes for RT-qPCR experiments for the normalization of equine milk somatic cells revealed some differences between the outcomes of the applied algorithms, although in both cases the KRT8 and TOP2B genes were pointed as the most stable. Analysis by geNorm showed that the combination of 4 reference genes (ACTB, GAPDH, TOP2B and KRT8 is required for apropriate RT-qPCR experiments normalization, whereas NormFinder algorithm pointed the combination of KRT8 and RPS9 genes as the most suitable. The trial study of the relative transcript abundance of the beta-casein gene with the use of various types and numbers of internal control genes confirmed once again that the selection of proper reference gene combinations is crucial for the final results of each real-time PCR experiment.
Jiang, Ming; Li, Haiyan; Zhang, Yongchun; Yang, Ying; Lu, Rong; Liu, Kuancan; Lin, Sijie; Lan, Xiaopeng; Wang, Haikun; Wu, Han; Zhu, Jian; Zhou, Zhongren; Xu, Jianming; Lee, Dong-Kee; Zhang, Lanjing; Lee, Yuan-Cho; Yuan, Jingsong; Abrams, Julian A.; Wang, Timothy G.; Sepulveda, Antonia R.; Wu, Qi; Chen, Huaiyong; Sun, Xin; She, Junjun; Chen, Xiaoxin; Que, Jianwen
In several organ systems the transitional zone between different types of epithelia is a hotspot for pre-neoplastic metaplasia and malignancy1–3. However, the cell-of-origin for the metaplastic epithelium and subsequent malignancy, remains obscure1–3. In the case of Barrett’s oesophagus (BE), intestinal metaplasia occurs at the gastro-oesophageal junction, where stratified squamous epithelium transitions into simple columnar cells4. Based on different experimental models, several alternative cell types have been proposed as the source of the metaplasia, but in all cases the evidence is inconclusive and no model completely mimics BE with the presence of intestinal goblet cells5–8. Here, we describe a novel transitional columnar epithelium with distinct basal progenitor cells (p63+ KRT5+ KRT7+) in the squamous-columnar junction (SCJ) in the upper gastrointestinal tract of the mouse. We use multiple models and lineage tracing strategies to show that this unique SCJ basal cell population serves as a source of progenitors for the transitional epithelium. Moreover, upon ectopic expression of CDX2 these transitional basal progenitors differentiate into intestinal-like epithelium including goblet cells, thus reproducing Barrett’s metaplasia. A similar transitional columnar epithelium is present at the transitional zones of other mouse tissues, including the anorectal junction, and, importantly, at the gastro-oesophageal junction in the human gut. Acid reflux-induced oesophagitis and the multilayered epithelium (MLE) believed to be a precursor of BE are both characterized by the expansion of the transitional basal progenitor cells. Taken together our findings reveal the presence of a previously unidentified transitional zone in the epithelium of the upper gastrointestinal tract and provide evidence that the p63+ KRT7+ basal cells in this zone are the cell-of-origin for MLE and BE. PMID:29019984
Gary A Clawson
Full Text Available Circulating tumor cells (CTCs are of recognized importance for diagnosis and prognosis of cancer patients. With melanoma, most studies do not show any clear relationship between CTC levels and stage of disease. Here, CTCs were enriched (∼400X from blood of melanoma patients using a simple centrifugation device (OncoQuick, and 4 melanocyte target RNAs (TYR, MLANA, MITF, and MIF were quantified using QPCR. Approximately one-third of melanoma patients had elevated MIF and MLANA transcripts (p<0.0001 and p<0.001, respectively compared with healthy controls. In contrast, healthy controls had uniformly higher levels of TYR and MITF than melanoma patients (p<0.0001. There was a marked shift of leukocytes into the CTC-enriched fractions (a 430% increase in RNA recovery, p<0.001, and no relationship between CTC levels and stage of disease was found. CTCs were captured on microfabricated filters and cultured. Captured melanoma CTCs were large cells, and consisted of 2 subpopulations, based on immunoreactivity. One subpopulation (∼50% stained for both pan-cytokeratin (KRT markers and the common leukocyte marker CD-45, whereas the second subpopulation stained for only KRT. Since similar cells are described in many cancers, we also examined blood from colorectal and pancreatic cancer patients. We observed analogous results, with most captured CTCs staining for both CD-45/KRT markers (and for the monocyte differentiation marker CD-14. Our results suggest that immature melanocyte-related cells (expressing TYR and MITF RNA may circulate in healthy controls, although they are not readily detectable without considerable enrichment. Further, as early-stage melanomas develop, immature melanocyte migration into the blood is somehow curtailed, whereas a significant proportion of patients develop elevated CTC levels (based on MIF and MLANA RNAs. The nature of the captured CTCs is consistent with literature describing leukocyte/macrophage-tumor cell fusion hybrids
Harun, Mohd Hairul Nizam; Sepian, Siti Norzalehawati; Chua, Kien-Hui; Ropilah, Abd Rahman; Abd Ghafar, Norzana; Che-Hamzah, Jemaima; Bt Hj Idrus, Ruszymah; Annuar, Faridah Hanom
The anterior surface of the eye is covered by several physically contiguous but histologically distinguishable epithelia overlying the cornea, limbus, bulbar conjunctiva, fornix conjunctiva, and palpebral conjunctiva. The self-renewing nature of the conjunctival epithelia makes their long-term survival ultimately dependent on small populations of stem cells. Hence, the objective of this study was to investigate the expression of the stem cell genes Sox2, OCT4, NANOG, Rex1, NES, and ABCG2 in cultured human conjunctival epithelium from different conjunctival zones, namely, the bulbar, palpebral and fornix zones. Three samples were taken from patients with primary pterygium and cataract (age range 56-66 years) who presented to our eye clinic at the UKM Medical Centre. The eye was examined with slit lamp to ensure there was no underlying ocular surface diseases and glaucoma. Conjunctival tissue was taken from patients who underwent a standard cataract or pterygium operation as a primary procedure. Tissues were digested, cultured, and propagated until an adequate number of cells was obtained. Total RNA was extracted and subjected to expression analysis of conjunctival epithelium genes (KRT4, KRT13, KRT19) and stem cell genes (Sox2, OCT4, NANOG, Rex1, NES, ABCG2) by reverse transcriptase-PCR and 2% agarose gel electrophoresis. The expression of Sox2, OCT4, and NANOG genes were detected in the fornical cells, while bulbar cells only expressed Sox2 and palpebral cells only expressed OCT4. Based on these results, the human forniceal region expresses a higher number of stem cell genes than the palpebral and bulbar conjunctiva.
Guo, Zhiling; Hu, Qin; Tian, Jijing; Yan, Li; Jing, Chuanyong; Xie, Heidi Qunhui; Bao, Wenjun; Rice, Robert H; Zhao, Bin; Jiang, Guibin
Proteomics technology is an attractive biomarker candidate discovery tool that can be applied to study large sets of biological molecules. To identify novel biomarkers and molecular targets in arsenic-induced skin lesions, we have determined the protein profile of arsenic-affected human epidermal stratum corneum by shotgun proteomics. Samples of palm and foot sole from healthy subjects were analyzed, demonstrating similar protein patterns in palm and sole. Samples were collected from the palms of subjects with arsenic keratosis (lesional and adjacent non-lesional samples) and arsenic-exposed subjects without lesions (normal). Samples from non-exposed healthy individuals served as controls. We found that three proteins in arsenic-exposed lesional epidermis were consistently distinguishably expressed from the unaffected epidermis. One of these proteins, the cadherin-like transmembrane glycoprotein, desmoglein 1 (DSG1) was suppressed. Down-regulation of DSG1 may lead to reduced cell-cell adhesion, resulting in abnormal epidermal differentiation. The expression of keratin 6c (KRT6C) and fatty acid binding protein 5 (FABP5) were significantly increased. FABP5 is an intracellular lipid chaperone that plays an essential role in fatty acid metabolism in human skin. This raises a possibility that overexpression of FABP5 may affect the proliferation or differentiation of keratinocytes by altering lipid metabolism. KRT6C is a constituent of the cytoskeleton that maintains epidermal integrity and cohesion. Abnormal expression of KRT6C may affect its structural role in the epidermis. Our findings suggest an important approach for future studies of arsenic-mediated toxicity and skin cancer, where certain proteins may represent useful biomarkers of early diagnoses in high-risk populations and hopefully new treatment targets. Further studies are required to understand the biological role of these markers in skin pathogenesis from arsenic exposure. Copyright © 2016 Elsevier Ltd
Full Text Available Berit T Valeberg,1 Lise H Høvik,2 Kari H Gjeilo3–6 1Faculty of Nursing, Oslo and Akershus University College of Applied Sciences, Oslo, 2Clinic of Anaesthesia and Intensive Care Medicine, St. Olavs Hospital, Trondheim University Hospital, 3Department of Cardiothoracic Surgery, 4Department of Cardiology, 5National Competence Centre for Complex Symptom Disorders, St. Olavs Hospital, Trondheim University Hospital, 6Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway Background and purpose: This was a prospective cohort study assessing data from 71 adult patients undergoing total knee arthroplasty (TKA following a standardized fast-track program between January and July 2013. The objective was to examine the relationship between self-rated pain sensitivity, as measured by the Pain Sensitivity Questionnaire (PSQ, and postoperative pain after TKA. Methods: The baseline questionnaires, PSQ and Brief Pain Inventory, were given to the patients for self-administration at the presurgical evaluation (1–2 weeks prior to surgery. The follow-up questionnaire, Brief Pain Inventory, was administered at the first follow-up, 8 weeks after surgery. Results: A statistically significant association was found between average preoperative pain and average pain 8 weeks after surgery (P=0.001. The PSQ-minor was statistically significantly associated with average pain only for patients younger than 70 years (P=0.03. Interpretation: This is the first study to examine the relationship between pain sensitivity measured by PSQ and postoperative pain in patients after TKA. We found that a lower score on the PSQ-minor was statistically significantly associated with patients’ pain 8 weeks after TKA surgery, but only for younger patients. Further research is needed to explore whether the PSQ could be a useful screening tool for patients’ pain sensitivity in clinical settings. Keywords
Ehlers, Niels; Hjortdal, Jesper; Nielsen, Kim
symptoms often include blurred vision and ocular irritation. Typical cases may be entirely free of complaints. Intermittent pain episodes, such as occur in recurrent erosion syndrome, are not the rule. Genetic sequencing indicated a familial relationship with the originally described Meesmann family......'s dystrophy occurs worldwide. The largest family described is the original German one, now supplemented with a Danish branch. Despite the presence of an identical genetic defect, the clinical phenotype varies. This suggests that non-KRT12-related mechanisms are responsible for the variation....
30 M. Nikolo: Effect of Texture and Density on Grain Coupling of Sintered Y-Ba-Cu-O Superconductors 11:30 - 12:00 A. SzAsz : The Symmetries and High...The Hall coefficient is always positive and obeys the RH (x T- 1 law . The I Hall mobility p2-I2 < I cm2/V.S. At T < Tc, the thermoelectric power equals...461561 80-6550 Prof. A. Szasz PP Dr. Martin Schwarz PP Eotvos University Angewandte Physik Muzeum Krt. 6-8 Hoechst AG H-1088 Budapest Hungary Gebaeude
Grams, Morgan E; Sang, Yingying; Ballew, Shoshana H; Carrero, Juan Jesus; Djurdjev, Ognjenka; Heerspink, Hiddo J L; Ho, Kevin; Ito, Sadayoshi; Marks, Angharad; Naimark, David; Nash, Danielle M; Navaneethan, Sankar D; Sarnak, Mark; Stengel, Benedicte; Visseren, Frank L J; Wang, Angela Yee-Moon; Köttgen, Anna; Levey, Andrew S; Woodward, Mark; Eckardt, Kai-Uwe; Hemmelgarn, Brenda; Coresh, Josef
Patients with chronic kidney disease and severely decreased glomerular filtration rate (GFR) are at high risk for kidney failure, cardiovascular disease (CVD) and death. Accurate estimates of risk and timing of these clinical outcomes could guide patient counseling and therapy. Therefore, we developed models using data of 264,296 individuals in 30 countries participating in the international Chronic Kidney Disease Prognosis Consortium with estimated GFR (eGFR)s under 30 ml/min/1.73m 2 . Median participant eGFR and urine albumin-to-creatinine ratio were 24 ml/min/1.73m 2 and 168 mg/g, respectively. Using competing-risk regression, random-effect meta-analysis, and Markov processes with Monte Carlo simulations, we developed two- and four-year models of the probability and timing of kidney failure requiring kidney replacement therapy (KRT), a non-fatal CVD event, and death according to age, sex, race, eGFR, albumin-to-creatinine ratio, systolic blood pressure, smoking status, diabetes mellitus, and history of CVD. Hypothetically applied to a 60-year-old white male with a history of CVD, a systolic blood pressure of 140 mmHg, an eGFR of 25 ml/min/1.73m 2 and a urine albumin-to-creatinine ratio of 1000 mg/g, the four-year model predicted a 17% chance of survival after KRT, a 17% chance of survival after a CVD event, a 4% chance of survival after both, and a 28% chance of death (9% as a first event, and 19% after another CVD event or KRT). Risk predictions for KRT showed good overall agreement with the published kidney failure risk equation, and both models were well calibrated with observed risk. Thus, commonly-measured clinical characteristics can predict the timing and occurrence of clinical outcomes in patients with severely decreased GFR. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
Navarro, Antonia; Yin, Ping; Monsivais, Diana; Lin, Simon M.; Du, Pan; Wei, Jian-Jun; Bulun, Serdar E.
Background Uterine leiomyomas, or fibroids, represent the most common benign tumor of the female reproductive tract. Fibroids become symptomatic in 30% of all women and up to 70% of African American women of reproductive age. Epigenetic dysregulation of individual genes has been demonstrated in leiomyoma cells; however, the in vivo genome-wide distribution of such epigenetic abnormalities remains unknown. Principal Findings We characterized and compared genome-wide DNA methylation and mRNA expression profiles in uterine leiomyoma and matched adjacent normal myometrial tissues from 18 African American women. We found 55 genes with differential promoter methylation and concominant differences in mRNA expression in uterine leiomyoma versus normal myometrium. Eighty percent of the identified genes showed an inverse relationship between DNA methylation status and mRNA expression in uterine leiomyoma tissues, and the majority of genes (62%) displayed hypermethylation associated with gene silencing. We selected three genes, the known tumor suppressors KLF11, DLEC1, and KRT19 and verified promoter hypermethylation, mRNA repression and protein expression using bisulfite sequencing, real-time PCR and western blot. Incubation of primary leiomyoma smooth muscle cells with a DNA methyltransferase inhibitor restored KLF11, DLEC1 and KRT19 mRNA levels. Conclusions These results suggest a possible functional role of promoter DNA methylation-mediated gene silencing in the pathogenesis of uterine leiomyoma in African American women. PMID:22428009
Khan, Anwar Kamal; Muhammad, Noor; Aziz, Abdul; Khan, Sher Alam; Shah, Khadim; Nasir, Abdul; Khan, Muzammil Ahmad; Khan, Saadullah
Pure hair and nail ectodermal dysplasia (PHNED) is a congenital disorder of hair abnormalities and nail dysplasia. Both autosomal recessive and dominant inheritance fashion of PHNED occurs. In literature, to date, five different forms of PHNED have been reported at molecular level, having three genes known and two loci with no gene yet. In this study, a four generations consanguineous family of Pakistani origin with autosomal recessive PHNED was investigated. Affected members exhibited PHNED phenotypes with involvement of complete hair loss and nail dysplasia. To screen for mutation in the genes (HOXC13, KRT74, KRT85), its coding exons and exons-intron boundaries were sequenced. The 3D models of normal and mutated HOXC13 were predicted by using homology modeling. Through investigating the family to known loci, the family was mapped to ectodermal dysplasia 9 (ECTD9) loci with genetic address of 12q13.13. Mutation screening revealed a novel missense mutation (c.929A > C; p.Asn310Thr) in homeobox DNA binding domain of HOXC13 gene in affected members of the family. Due to mutation, loss of hydrogen bonding and difference in potential energy occurs, which may resulting in alteration of protein function. This is the first mutation reported in homeodomain, while 5 th mutation reported in HOXC13 gene causing PHNED.
Full Text Available The in situ proximity ligation assay (isPLA is an increasingly used technology for in situ detection of protein interactions, post-translational modifications, and spatial relationships of antigens in cells and tissues, in general. In order to test its performance we compared isPLA with immunofluorescence microscopy by analyzing protein interactions in cytoplasmic protein aggregates, so-called Mallory Denk bodies (MDBs. These structures represent protein inclusions in hepatocytes typically found in human steatohepatitis and they can be generated in mice by feeding of 3,5-diethoxy-carbonyl-1,4-dihydrocollidine (DDC. We investigated the colocalization of all three key MDB components, namely keratin 8 (K8, keratin 18 (K18, and p62 (sequestosome 1 by isPLA and immunofluorescence microscopy. Sensitivity and specificity of isPLA was assessed by using Krt8-/- and Krt18-/- mice as biological controls, along with a series of technical controls. isPLA signal visualization is a robust technology with excellent sensitivity and specificity. The biological relevance of signals generated critically depends on the performance of antibodies used, which requires careful testing of antibodies like in immunofluorescence microscopy. There is a clear advantage of isPLA in visualizing protein co-localization, particularly when antigens are present at markedly different concentrations. Furthermore, isPLA is superior to confocal microscopy with respect to spatial resolution of colocalizing antigens. Disadvantages compared to immunofluorescence are increased costs and longer duration of the laboratory protocol.
Sharafat, Shahram; Takahashi, Akiyuki; Nagasawa, Koji; Ghoniem, Nasr
Low energy (<100 keV) helium implantation of tungsten has been shown to result in the formation of unusual surface morphologies over a large temperature range (700-2100 deg. C). Simulation of these macroscopic phenomena requires a multiscale approach to modeling helium transport in both space and time. We present here a multiscale helium transport model by coupling spatially-resolved kinetic rate theory (KRT) with kinetic Monte Carlo (KMC) simulation to model helium bubble nucleation and growth. The KRT-based HEROS Code establishes defect concentrations as well as stable helium bubble nuclei as a function of implantation parameters and position from the implanted surface and the KMC-based Mc-HEROS Code models the growth of helium bubbles due to migration and coalescence. Temperature- and stress-gradients can act as driving forces, resulting in biased bubble migration. The Mc-HEROS Code was modified to simulate the impact of stress gradients on bubble migration and coalescence. In this work, we report on bubble growth and gas release of helium implanted tungsten W/O stress gradients. First, surface pore densities and size distributions are compared with available experimental results for stress-free helium implantation conditions. Next, the impact of stress gradients on helium bubble evolution is simulated. The influence of stress fields on bubble and surface pore evolution are compared with stress-free simulations. It is shown that near surface stress gradients accelerate helium bubbles towards the free surface, but do not increasing average bubble diameters significantly.
Zhu, Jie; Wang, Peng; Yu, Zhimin; Lai, Wei; Cao, Yi; Huang, Pinbo; Xu, Qiaodong; Yu, Menglei; Xu, Junyao; Huang, Zitong; Zeng, Bing
Diabetes mellitus is frequently accompanied by chronic complications like delayed wound healing, which is consider to be attributed to the accumulation of advanced glycosylation end product (AGE). However, the impacts of AGE on epidermal stem cells (ESCs) are largely unknown. This study aims to address the influence and mechanism of AGE on ESCs. ESCs isolated from rats were cultured in AGE-modified bovine serum albumin and transfected with small interfering RNA to knock down AGE-specific receptor (AGER). Expression of stem cell markers integrin β1 (ITGB1) and keratin 19 (KRT19), cell viability, apoptosis and reactive oxygen species (ROS) were examined. Wnt pathway-related factors Wnt family member 1 (WNT1), WNT3A, β-catenin, v-myc avian myelocytomatosis viral oncogene homolog (MYC), cyclin D1 (CCND1) and matrix metallopeptidase 7 (MMP7) were quantified. The interaction between forkhead box O1 (FOXO1) and β-catenin was assessed by co-immunoprecipitation. Results indicated that AGE down-regulated ITGB1 and KRT19 expression, suppressed ESC viability and promoted apoptosis, and ROS level ( P factor 1 to interact with β-catenin, which might help to elucidate the mechanism of AGE repressing ESCs. This study helps to understand the mechanism of accumulated AGE in affecting ESC capacities, and provides potential therapeutic targets to meliorate diabetic wound healing.
Rayner, Hugh C; Hollingworth, Lee; Higgins, Robert; Dodds, Simon
A significant proportion of patients with diabetes mellitus do not get the benefit of treatment that would reduce their risk of progressive kidney disease and reach a nephrologist once significant loss of kidney function has already occurred. Systematic disease management of patients with diabetes and kidney disease. Diverse population (approximately 800,000) in and around Birmingham, West Midlands, UK. Number of outpatient appointments, estimated glomerular filtration rate (eGFR) at first contact with nephrologist, number of patients starting kidney replacement therapy (KRT) and mode of KRT at start. Identification of patients with low or deteriorating trend in eGFR from weekly database review, specialist diabetes-kidney clinic, self-management of blood pressure and transfer to multidisciplinary clinic >12 months before end-stage kidney disease. New patients increased from 62 in 2003 to 132 in 2010; follow-ups fell from 251 to 174. Median eGFR at first clinic visit increased from 28.8 ml/min/1.73 m(2) (range 6.1-67.0) in 2000/2001 to 35.0 (11.1-147.5) in 2010 (pmanagement across a large population significantly improves patient outcomes, increases the productivity of a specialist service and could reduce healthcare costs compared with the current model of care.
Van Zeveren Alex
Full Text Available Abstract Background Normal preimplantation embryo development encompasses a series of events including first cleavage division, activation of the embryonic genome, compaction and blastocyst formation. First lineage differentiation starts at the blastocyst stage with the formation of the trophectoderm and the inner cell mass. The main objective of this study was the detection, identification and expression analysis of genes associated with blastocyst formation in order to help us better understand this process. This information could lead to improvements of in vitro embryo production procedures. Results A subtractive cDNA library was constructed enriched for transcripts preferentially expressed at the blastocyst stage compared to the 2-cell and 8-cell stage. Sequence information was obtained for 65 randomly selected clones. The RNA expression levels of 12 candidate genes were determined throughout 3 stages of preimplantation embryo development (2-cell, 8-cell and blastocyst and compared with the RNA expression levels of in vivo "golden standard" embryos using real-time PCR. The RNA expression profiles of 9 (75% transcripts (KRT18, FN1, MYL6, ATP1B3, FTH1, HINT1, SLC25A5, ATP6V0B, RPL10 were in agreement with the subtractive cDNA cloning approach, whereas for the remaining 3 (25% (ACTN1, COPE, EEF1A1 the RNA expression level was equal or even higher at the earlier developmental stages compared to the blastocyst stage. Moreover, significant differences in RNA expression levels were observed between in vitro and in vivo produced embryos. By immunofluorescent labelling, the protein expression of KRT18, FN1 and MYL6 was determined throughout bovine preimplantation embryo development and showed the same pattern as the RNA expression analyses. Conclusion By subtractive cDNA cloning, candidate genes involved in blastocyst formation were identified. For several candidate genes, important differences in gene expression were observed between in vivo and in
Full Text Available Abstract Background Invasive ductal and lobular carcinomas (IDC and ILC are the most common histological types of breast cancer. Clinical follow-up data and metastatic patterns suggest that the development and progression of these tumors are different. The aim of our study was to identify gene expression profiles of IDC and ILC in relation to normal breast epithelial cells. Methods We examined 30 samples (normal ductal and lobular cells from 10 patients, IDC cells from 5 patients, ILC cells from 5 patients microdissected from cryosections of ten mastectomy specimens from postmenopausal patients. Fifty nanograms of total RNA were amplified and labeled by PCR and in vitro transcription. Samples were analysed upon Affymetrix U133 Plus 2.0 Arrays. The expression of seven differentially expressed genes (CDH1, EMP1, DDR1, DVL1, KRT5, KRT6, KRT17 was verified by immunohistochemistry on tissue microarrays. Expression of ASPN mRNA was validated by in situ hybridization on frozen sections, and CTHRC1, ASPN and COL3A1 were tested by PCR. Results Using GCOS pairwise comparison algorithm and rank products we have identified 84 named genes common to ILC versus normal cell types, 74 named genes common to IDC versus normal cell types, 78 named genes differentially expressed between normal ductal and lobular cells, and 28 named genes between IDC and ILC. Genes distinguishing between IDC and ILC are involved in epithelial-mesenchymal transition, TGF-beta and Wnt signaling. These changes were present in both tumor types but appeared to be more prominent in ILC. Immunohistochemistry for several novel markers (EMP1, DVL1, DDR1 distinguished large sets of IDC from ILC. Conclusion IDC and ILC can be differentiated both at the gene and protein levels. In this study we report two candidate genes, asporin (ASPN and collagen triple helix repeat containing 1 (CTHRC1 which might be significant in breast carcinogenesis. Besides E-cadherin, the proteins validated on tissue
Turashvili, Gulisa; Srovnal, Josef; Hajduch, Marian; Murray, Paul; Kolar, Zdenek; Bouchal, Jan; Baumforth, Karl; Wei, Wenbin; Dziechciarkova, Marta; Ehrmann, Jiri; Klein, Jiri; Fridman, Eduard; Skarda, Jozef
Invasive ductal and lobular carcinomas (IDC and ILC) are the most common histological types of breast cancer. Clinical follow-up data and metastatic patterns suggest that the development and progression of these tumors are different. The aim of our study was to identify gene expression profiles of IDC and ILC in relation to normal breast epithelial cells. We examined 30 samples (normal ductal and lobular cells from 10 patients, IDC cells from 5 patients, ILC cells from 5 patients) microdissected from cryosections of ten mastectomy specimens from postmenopausal patients. Fifty nanograms of total RNA were amplified and labeled by PCR and in vitro transcription. Samples were analysed upon Affymetrix U133 Plus 2.0 Arrays. The expression of seven differentially expressed genes (CDH1, EMP1, DDR1, DVL1, KRT5, KRT6, KRT17) was verified by immunohistochemistry on tissue microarrays. Expression of ASPN mRNA was validated by in situ hybridization on frozen sections, and CTHRC1, ASPN and COL3A1 were tested by PCR. Using GCOS pairwise comparison algorithm and rank products we have identified 84 named genes common to ILC versus normal cell types, 74 named genes common to IDC versus normal cell types, 78 named genes differentially expressed between normal ductal and lobular cells, and 28 named genes between IDC and ILC. Genes distinguishing between IDC and ILC are involved in epithelial-mesenchymal transition, TGF-beta and Wnt signaling. These changes were present in both tumor types but appeared to be more prominent in ILC. Immunohistochemistry for several novel markers (EMP1, DVL1, DDR1) distinguished large sets of IDC from ILC. IDC and ILC can be differentiated both at the gene and protein levels. In this study we report two candidate genes, asporin (ASPN) and collagen triple helix repeat containing 1 (CTHRC1) which might be significant in breast carcinogenesis. Besides E-cadherin, the proteins validated on tissue microarrays (EMP1, DVL1, DDR1) may represent novel
Krueger, James; Clark, James D; Suárez-Fariñas, Mayte; Fuentes-Duculan, Judilyn; Cueto, Inna; Wang, Claire Q; Tan, Huaming; Wolk, Robert; Rottinghaus, Scott T; Whitley, Maryann Z; Valdez, Hernan; von Schack, David; O'Neil, Shawn P; Reddy, Padmalatha S; Tatulych, Svitlana
Tofacitinib is an oral Janus kinase inhibitor being investigated for psoriasis. We sought to elucidate the molecular mechanisms underlying the clinical efficacy of tofacitinib in patients with psoriasis. Twelve patients with plaque psoriasis were randomized (3:1) to receive 10 mg of tofacitinib or placebo twice daily for 12 weeks. Biopsy specimens were taken from nonlesional (baseline) and lesional (baseline, days 1 and 3, and weeks 1, 2, 4, and 12) skin. Biopsy specimens were examined for psoriatic epidermal features (thickness, Ki67(+) keratinocytes and keratin 16 [KRT16] mRNA expression, and phosphorylated signal transducer and activator of transcription [pSTAT](+) nuclei) and T-cell and dendritic cell (DC) subsets by using immunohistochemistry, and mRNA transcripts were quantified by using a microarray. In lesional skin keratinocyte pSTAT1 and pSTAT3 staining was increased at baseline but reduced after 1 day of tofacitinib (baseline, median of 1290 pSTAT1(+) cells/μm(2); day 1, median of 332 pSTAT1(+) cells/μm(2); and nonlesional, median of 155 pSTAT1(+) cells/μm(2)). Epidermal thickness and KRT16 mRNA expression were significantly and progressively reduced after days 1 and 3 of tofacitinib administration, respectively (eg, KRT16 decreased 2.74-fold, day 3 vs baseline, P = .016). Decreases in DC and T-cell numbers were observed after weeks 1 and 2, respectively. At week 4, significant decreases in IL-23/TH17 pathways were observed that persisted through week 12. Improvements in clinical and histologic features were strongly associated with changes in expression of psoriasis-related genes and reduction in IL-17 gene expression. Tofacitinib has a multitiered response in patients with psoriasis: (1) rapid attenuation of keratinocyte Janus kinase/STAT signaling; (2) removal of keratinocyte-induced cytokine signaling, leading to reductions in pathologic DC and T-cell numbers to nonlesional levels; and (3) inhibition of the IL-23/TH17 pathway. Copyright © 2016
Full Text Available Knut A Hestad,1–3 Siri Weider,3,4 Kristian Bernhard Nilsen,5–7 Marit Sæbø Indredavik,8,9 Trond Sand7,10 1Department of Research, Innlandet Hospital Trust, Brumunddal, Norway; 2Department of Public Health, Hedmark University of Applied Sciences, Elverum, Norway; 3Department of Psychology, Faculty of Social Sciences and Technology Management, Norwegian University of Science and Technology (NTNU, Trondheim, Norway; 4Department of Psychiatry, Specialised Unit for Eating Disorder Patients, Levanger Hospital, Health Trust Nord-Trøndelag, Levanger, Norway; 5Department of Neuroscience, Norwegian University of Science and Technology (NTNU, Trondheim, Norway; 6Department of Work Psychology and Physiology, National Institute of Occupational Health, Oslo, Norway; 7Department of Neurology, Section for Clinical Neurophysiology, Oslo University Hospital, Ullevål, Oslo, Norway; 8Regional Centre for Child and Youth Mental Health and Child Welfare, Faculty of Medicine, Norwegian University of Science and Technology (NTNU, Trondheim, Norway; 9Department of Child and Adolescent Psychiatry, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway; 10Department of Neurology and Clinical Neurophysiology, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway Objective: To conduct a blind study of quantitative electroencephalogram-band amplitudes in patients with anorexia nervosa (AN and healthy controls.Methods: Twenty-one patients with AN and 24 controls were examined with eyes-closed 16-channel electroencephalogram. Main variables were absolute alpha, theta, and delta amplitudes in frontal, temporal, and posterior regions.Results: There were no significant differences between the AN patients and controls regarding absolute regional band amplitudes in µV. Borderline significance was found for anterior theta (P=0.051. Significantly increased left and right frontal electrode theta amplitude was found in AN patients (F3, P=0.014; F4, P
Full Text Available This issue of Seminar.net contains three articles that were written in connection with a Norwegian e-learning conference titled “Networked collaboration, sharing and response”. The conference was held in Mars 2008 in Trondheim, and the presentations from the conference is available (in norwegian language at http://www.nvu.no. Networked collaboration was chosen as a theme because collaboration is important to achieve learning, according to the social-constructivistic pedagogy that has a strong standing in Norway, but how should this occur on the net? Sharing of content, as in digital learning resources, is a phenomenon with increasing popularity as described in the OECD-report “Giving Knowledge for Free”. But to achieve reuse of content, not only publishing it, it is important with a networked community where the plethora of information can be sorted with relevance to specific topics. Response is about guiding, coaching and tutoring. In what ways may resources and tools be used to move in the direction of solving Bloom’s two sigma problem/challenge? The first article, by Morten Flate Paulsen, shows how cooperative learning can be implemented successfully so that students have optimal individual freedom within online learning communities. The second article, by Carl F. Dons, shows how student teachers can be prepared to deal with pupils who have a wide range of experiences of the digital world. The third and last article, by Kristin Dale, is sharing experiences with multiple choice-tests to give midterm responses to students. In addition, this issue has a commentary article by Rune Krumsvik discussing the need to develop new practices for teachers and students on the background of the digital developments. The conference and articles covers three big themes. It may be difficult to find more important issues, apart from finding money and time to support its development. Olav Skundberg, guest editorAssociate professor
exosomes. B. Dynamic light scattering (DLS) showing the size of the exosomes. 6 Histone H4 OS=Homo sapiens GN=HIST1H4A PE=1 SV=2 H4_HUMAN Keratin, type I...cytoskeletal 9 OS=Homo sapiens GN=KRT9 PE=1 SV=3 K1C9_HUMAN Isoform 2 of Clathrin heavy chain 1 OS=Homo sapiens GN=CLTC sp|Q00610-2|CLH1_HUMAN (+1...Clathrin heavy chain 2 OS=Homo sapiens GN=CLTCL1 PE=1 SV=2 sp|P53675|CLH2_HUMAN Cluster of Histone H2A type 1-B/E OS=Homo sapiens GN=HIST1H2AB PE=1 SV
Persuhn, D C; Souza, E M; Steffens, M B; Pedrosa, F O; Yates, M G; Rigo, L U
The role of the Ntr system in Herbaspirillum seropedicae was determined via ntrB and ntrC mutants. Three phenotypes were identified in these mutants: Nif(-), deficiency in growth using nitrate, and low glutamine synthetase (GS) activity. All phenotypes were restored by the plasmid pKRT1 containing the intact glnA, ntrB and ntrC genes of H. seropedicae. The promoter region of glnA was subcloned into a beta-galactosidase fusion vector and the results suggested that NtrC positively regulates the glnA promoter in response to low nitrogen. The H. seropedicae ntrC and ntrB mutant strains showed a deficiency of adenylylation/deadenylylation of GS, indicating that NtrC and NtrB are involved in both transcription and activity control of GS in this organism.
Full Text Available Circulating tumor cells (CTCs are becoming a scientifically recognized indicator of primary tumors and/or metastasis. These cells can now be accurately detected and characterized as the result of technological advances. We analyzed the presence of CTCs in the peripheral blood of patients with metastatic breast cancer by real-time reverse-transcription PCR (RT-qPCR using a panel of selected genes. The analysis of a single marker, without an EpCAM based enrichment approach, allowed the positive identification of 35% of the metastatic breast cancer patients. The analysis of five genes (SCGB2, TFF1, TFF3, Muc1, KRT20 performed in all the samples increased the detection to 61%. We describe a sensitive, reproducible and easy to implement approach to characterize CTC in patients with metastasic breast cancer.
Therkildsen, Christina; Eriksson, Pontus; Höglund, Mattias
Lynch syndrome confers an increased risk for urothelial carcinoma (UC). Molecular subtypes may be relevant to prognosis and therapeutic possibilities, but have to date not been defined in Lynch syndrome-associated urothelial cancer. We aimed to provide a molecular description of Lynch syndrome......-associated UC. Thus, Lynch syndrome-associated UC of the upper urinary tract and the urinary bladder were identified in the Danish hereditary non-polyposis colorectal cancer (HNPCC) register and were transcriptionally and immunohistochemically profiled and further related to data from 307 sporadic urothelial...... carcinomas. Whole genome mRNA expression profiles of 41 tumors and immunohistochemical stainings against FGFR3, KRT5, CCNB1, RB1, and CDKN2A (p16) of 37 tumors from Lynch syndrome patients were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data was analyzed...
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Hiram Larangeira de Almeida Jr
Full Text Available O estudo das alterações moleculares das epidermólises bolhosas tem contribuído para que se compreenda melhor essas enfermidades. Na epidermólise bolhosa simples a maioria dos casos está associada com alteração nas citoqueratinas basais 5 (gen KRT5 e 14 (gen KRT14, o que modifica o citoesqueleto na camada basal da epiderme, levando à degeneração dessa camada, formando bolha intra-epidérmica. Mutações na plectina (gen PLEC1, componente da placa interna do hemidesmossoma, levam também à clivagem intra-epidérmica. Na epidermólise bolhosa juncional vários gens estão envolvidos, em decorrência da complexidade da zona da membrana basal, todos levando ao descolamento dos queratinócitos basais na lâmina lúcida, pela disfunção da aderência entre esses e a lâmina densa. Alterações na laminina 5 (gens LAMA3, LAMB3 e LAMC2, integrina alfa6beta4 (gens ITGA6 e ITGB4 e colágeno XVII (gen COL17A1 foram descritas. Por fim, na epidermólise bolhosa distrófica apenas um gen está mutado, alterando o colágeno VII (gen COL7A1, principal componente das fibrilas ancorantes, produzindo clivagem abaixo da lâmina densa, variando fenotipicamente de acordo com a conseqüência da mutação. Outra aplicação importante dessas informações refere-se ao diagnóstico pré-natal, com a perspectiva no futuro da terapia gênica.New data regarding the molecular aspects of the heterogeneous group of epidermolysis bullosa has brought some important information about its pathogenesis. In epidermolysis bullosa simplex the majority of mutations are localized in the genes of the basal cytokeratin 5 (gene KRT5 and 14 (gene KRT14, cytolysis at this layer with intraepidermal blister is seen under light microscopy. Mutations of plectin (gene PLEC1, a protein found in the inner hemidesmosomal plaque, leads also to intraepidermal blisters. In junctional epidermolysis bullosa many proteins from the basal membrane zone are involved, such as laminin 5 (genes
Full Text Available The IKKβ is known to regulate transcription factor NF-κB activation leading to inflammatory responses. Recent gene knockout studies have shown that IKKβ can orchestrate local inflammatory responses and regulate homeostasis of epithelial tissues. To investigate whether IKKβ has an intrinsic role in epithelial cells, we established an in vivo system in the immune privileged corneal epithelium. We generated triple transgenic Krt12(rtTA/rtTAt/tet-O-Cre/Ikkβ(F/F (Ikkβ(ΔCE/ΔCE mice by crossing the Krt12-rtTA knock-in mice, which express the reverse tetracycline transcription activator in corneal epithelial cells, with the tet-O-Cre and Ikkβ(F/F mice. Doxycycline-induced IKKβ ablation occurred in corneal epithelial cells of triple transgenic Ikkβ(ΔCE/ΔCE mice, but loss of IKKβ did not cause ocular abnormalities in fetal development and postnatal maintenance. Instead, loss of IKKβ significantly delayed healing of corneal epithelial debridement without affecting cell proliferation, apoptosis or macrophage infiltration. In vitro studies with human corneal epithelial cells (HCEpi also showed that IKKβ was required for cytokine-induced cell migration and wound closure but was dispensable for cell proliferation. In both in vivo and in vitro settings, IKKβ was required for optimal activation of NF-κB and p38 signaling in corneal epithelial cells, and p38 activation is likely mediated through formation of an IKKβ-p38 protein complex. Thus, our studies in corneal epithelium reveal a previously un-recognized role for IKKβ in the control of epithelial cell motility and wound healing.
Basmanav, F. Buket; Oprisoreanu, Ana-Maria; Pasternack, Sandra M.; Thiele, Holger; Fritz, Günter; Wenzel, Jörg; Größer, Leopold; Wehner, Maria; Wolf, Sabrina; Fagerberg, Christina; Bygum, Anette; Altmüller, Janine; Rütten, Arno; Parmentier, Laurent; El Shabrawi-Caelen, Laila; Hafner, Christian; Nürnberg, Peter; Kruse, Roland; Schoch, Susanne; Hanneken, Sandra; Betz, Regina C.
Dowling-Degos disease (DDD) is an autosomal-dominant genodermatosis characterized by progressive and disfiguring reticulate hyperpigmentation. We previously identified loss-of-function mutations in KRT5 but were only able to detect pathogenic mutations in fewer than half of our subjects. To identify additional causes of DDD, we performed exome sequencing in five unrelated affected individuals without mutations in KRT5. Data analysis identified three heterozygous mutations from these individuals, all within the same gene. These mutations, namely c.11G>A (p.Trp4∗), c.652C>T (p.Arg218∗), and c.798-2A>C, are within POGLUT1, which encodes protein O-glucosyltransferase 1. Further screening of unexplained cases for POGLUT1 identified six additional mutations, as well as two of the above described mutations. Immunohistochemistry of skin biopsies of affected individuals with POGLUT1 mutations showed significantly weaker POGLUT1 staining in comparison to healthy controls with strong localization of POGLUT1 in the upper parts of the epidermis. Immunoblot analysis revealed that translation of either wild-type (WT) POGLUT1 or of the protein carrying the p.Arg279Trp substitution led to the expected size of about 50 kDa, whereas the c.652C>T (p.Arg218∗) mutation led to translation of a truncated protein of about 30 kDa. Immunofluorescence analysis identified a colocalization of the WT protein with the endoplasmic reticulum and a notable aggregating pattern for the truncated protein. Recently, mutations in POFUT1, which encodes protein O-fucosyltransferase 1, were also reported to be responsible for DDD. Interestingly, both POGLUT1 and POFUT1 are essential regulators of Notch activity. Our results furthermore emphasize the important role of the Notch pathway in pigmentation and keratinocyte morphology. PMID:24387993
Permuth, Jennifer B.; Pirie, Ailith; Ann Chen, Y.; Lin, Hui-Yi; Reid, Brett M.; Chen, Zhihua; Monteiro, Alvaro; Dennis, Joe; Mendoza-Fandino, Gustavo; Anton-Culver, Hoda; Bandera, Elisa V.; Bisogna, Maria; Brinton, Louise; Brooks-Wilson, Angela; Carney, Michael E.; Chenevix-Trench, Georgia; Cook, Linda S.; Cramer, Daniel W.; Cunningham, Julie M.; Cybulski, Cezary; D’Aloisio, Aimee A.; Anne Doherty, Jennifer; Earp, Madalene; Edwards, Robert P.; Fridley, Brooke L.; Gayther, Simon A.; Gentry-Maharaj, Aleksandra; Goodman, Marc T.; Gronwald, Jacek; Hogdall, Estrid; Iversen, Edwin S.; Jakubowska, Anna; Jensen, Allan; Karlan, Beth Y.; Kelemen, Linda E.; Kjaer, Suzanne K.; Kraft, Peter; Le, Nhu D.; Levine, Douglas A.; Lissowska, Jolanta; Lubinski, Jan; Matsuo, Keitaro; Menon, Usha; Modugno, Rosemary; Moysich, Kirsten B.; Nakanishi, Toru; Ness, Roberta B.; Olson, Sara; Orlow, Irene; Pearce, Celeste L.; Pejovic, Tanja; Poole, Elizabeth M.; Ramus, Susan J.; Anne Rossing, Mary; Sandler, Dale P.; Shu, Xiao-Ou; Song, Honglin; Taylor, Jack A.; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J.; Tworoger, Shelley S.; Webb, Penelope M.; Wentzensen, Nicolas; Wilkens, Lynne R.; Winham, Stacey; Woo, Yin-Ling; Wu, Anna H.; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Phelan, Catherine M.; Schildkraut, Joellen M.; Berchuck, Andrew; Goode, Ellen L.; Pharoah, Paul D. P.; Sellers, Thomas A.
Rare and low frequency variants are not well covered in most germline genotyping arrays and are understudied in relation to epithelial ovarian cancer (EOC) risk. To address this gap, we used genotyping arrays targeting rarer protein-coding variation in 8,165 EOC cases and 11,619 controls from the international Ovarian Cancer Association Consortium (OCAC). Pooled association analyses were conducted at the variant and gene level for 98,543 variants directly genotyped through two exome genotyping projects. Only common variants that represent or are in strong linkage disequilibrium (LD) with previously-identified signals at established loci reached traditional thresholds for exome-wide significance (P P≥5.0 ×10 − 7) were detected for rare and low-frequency variants at 16 novel loci. Four rare missense variants were identified (ACTBL2 rs73757391 (5q11.2), BTD rs200337373 (3p25.1), KRT13 rs150321809 (17q21.2) and MC2R rs104894658 (18p11.21)), but only MC2R rs104894668 had a large effect size (OR = 9.66). Genes most strongly associated with EOC risk included ACTBL2 (PAML = 3.23 × 10 − 5; PSKAT-o = 9.23 × 10 − 4) and KRT13 (PAML = 1.67 × 10 − 4; PSKAT-o = 1.07 × 10 − 5), reaffirming variant-level analysis. In summary, this large study identified several rare and low-frequency variants and genes that may contribute to EOC susceptibility, albeit with possible small effects. Future studies that integrate epidemiology, sequencing, and functional assays are needed to further unravel the unexplained heritability and biology of this disease. PMID:27378695
Full Text Available In the developing peripheral nervous system, a coordinated reciprocal signaling between Schwann cells and axons is crucial for accurate myelination. The myelin and lymphocyte protein MAL is a component of lipid rafts that is important for targeting proteins and lipids to distinct domains. MAL overexpression impedes peripheral myelinogenesis, which is evident by a delayed onset of myelination and reduced expression of the myelin protein zero (Mpz/P0 and the low-affinity neurotrophin receptor p75NTR . This study shows that MAL overexpression leads to a significant reduction of Mpz and p75NTR expression in primary mouse Schwann cell cultures, which was already evident before differentiation, implicating an effect of MAL in early Schwann cell development. Their transcription was robustly reduced, despite normal expression of essential transcription factors and receptors. Further, the cAMP response element-binding protein (CREB and phosphoinositide 3-kinase signaling pathways important for Schwann cell differentiation were correctly induced, highlighting that other so far unknown rate limiting factors do exist. We identified novel genes expressed by Schwann cells in a MAL-dependent manner in vivo and in vitro. A number of those, including S100a4, RhoU and Krt23, are implicated in cytoskeletal organization and plasma membrane dynamics. We showed that S100a4 is predominantly expressed by nonmyelinating Schwann cells, whereas RhoU was localized within myelin membranes, and Krt23 was detected in nonmyelinating as well as in myelinating Schwann cells. Their differential expression during early peripheral nerve development further underlines their possible role in influencing Schwann cell differentiation and myelination.
Xu, Yan; Xie, Jianhui; Cao, Yu; Zhou, Huaigu; Ping, Yuan; Chen, Liankang; Gu, Lihua; Hu, Wei; Bi, Gang; Ge, Jianye; Chen, Xin; Zhao, Ziqin
The identification of human body fluids or tissues through mRNA-based profiling is very useful for forensic investigations. Previous studies have shown mRNA biomarkers are effective to identify the origin of biological samples. In this study, we selected 16 tissue specific biomarkers to evaluate their specificities and sensitivities for human body fluids and tissues identification, including porphobilinogen deaminase (PBGD), hemoglobin beta (HBB) and Glycophorin A (GLY) for circulatory blood, protamine 2 (PRM2) and transglutaminase 4 (TGM4) for semen, mucin 4 (MUC4) and human beta defensin 1(HBD1) for vaginal secretion, matrix metalloproteinases 7 and 11 (MMP7 and MMP11) for menstrual blood, keratin 4(KRT4) for oral mucosa, loricrin (LOR) and cystatin 6 (CST6) for skin, histatin 3(HTN3) for saliva, statherin (STATH) for nasal secretion, dermcidin (DCD) for sweat and uromodulin (UMOD) for urine. The above mentioned ten common forensic body fluids or tissues were used in the evaluation. Based on the evaluation, a reverse transcription (RT) PCR multiplex assay, XCYR1, which includes 12 biomarkers (i.e., HBB, GLY, HTN3, PRM2, KRT4, MMP11, MUC4, DCD, UMOD, MMP7, TGM4, and STATH) and 2 housekeeping genes [i.e., glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and 18SrRNA], was developed. This assay was further validated with real casework samples and mock samples (with both single source and mixture) and it was approved that XCYR1 is effective to identify common body fluids or tissues (i.e., circulatory blood, saliva, semen, vaginal secretion, menstrual blood, oral mucosa, nasal secretion, sweat and urine) in forensic casework samples. PMID:24991806
Gripp, Karen W; Ennis, Sara; Napoli, Joseph
Exome analysis has had a dramatic impact on genetic research. We present the application of such newly generated information to patient care. The patient was a female, born with normal growth parameters to nonconsanguineous parents after an uneventful pregnancy. She had bilateral cleft lip/palate and ankyloblepharon. Sparse hair, dysplastic nails and hypohidrosis were subsequently noted. With exception of speech related issues, her development was normal. A clinical diagnosis of ankyloblepharon-ectodermal defects-cleft lip/palate or Hay-Wells syndrome resulted in TP63 sequence analysis. TP63 sequence and deletion/duplication analysis of all coding exons had a normal result, as did chromosome and SNP array analysis. Diagnostic exome analysis revealed a heterozygous nonsense mutation in KRT83 categorized as deleterious and associated with monilethrix. In addition, a homozygous missense variant of unknown clinical significance was reported in RIPK4. Using research based exome analysis, RIPK4 had just a few months prior been identified as pathogenic for Bartsocas-Papas syndrome. While the clinical diagnostic report implied the KRT83 mutation as a more likely cause for the patient's phenotype, clinical correlation, literature review and use of computerized mutation analysis programs allowed us to identify the homozygous RIPK4 (c.488G > A; p.Gly163Asp) mutation as the underlying pathogenic change. Consequently, we expand the phenotype of Bartsocas-Papas syndrome to an attenuated presentation resembling Hay-Wells syndrome, lacking lethality and pterygia. In contrast to the autosomal dominant Hay-Wells syndrome, Bartsocas-Papas syndrome is autosomal recessive, implying a 25% recurrence risk. Copyright © 2013 Wiley Periodicals, Inc.
Duverger, Olivier; Beniash, Elia; Morasso, Maria I.
Dental enamel is a hardest tissue in the human body, and although it starts as a tissue rich in proteins, by the time of eruption of the tooth in the oral cavity only a small fraction of the protein remains. While this organic matrix of enamel represents less than 1% by weight it plays essential roles in improving both toughness and resilience to chemical attacks. Despite the fact that the first studies of the enamel matrix began in the 19th century its exact composition and mechanisms of its function remain poorly understood. It was proposed that keratin or a keratin-like primitive epithelial component exists in mature enamel, however due to the extreme insolubility of its organic matrix the presence of keratins there was never clearly established. We have recently identified expression of a number of hair keratins in ameloblasts, the enamel secreting cells, and demonstrated their incorporation into mature enamel. Mutation in epithelial hair keratin KRT75 leads to a skin condition called pseudofollicularis barbae. Carriers of this mutation have an altered enamel structure and mechanical properties. Importantly, these individuals have a much higher prevalence of caries. To the best of our knowledge, this is the first study showing a direct link between a mutation in a protein-coding region of a gene and increased caries rates. In this paper we present an overview of the evidence of keratin-like material in enamel that has accumulated over the last 150 years. Furthermore, we propose potential mechanisms of action of KTR75 in enamel and highlight the clinical implications of the link between mutations in KRT75 and caries. Finally, we discuss the potential use of keratins for enamel repair. PMID:26709044
El Sheikh Saad, H; Toullec, A; Vacher, S; Pocard, M; Bieche, I; Perrot-Applanat, M
Exposure to low doses of environmental estrogens such as bisphenol A and genistein (G) alters mammary gland development. The effects of environmental anti-androgens, such as the fungicide vinclozolin (V), on mammary gland morphogenesis are unknown. We previously reported that perinatal exposure to G, V, and the GV combination causes histological changes in the mammary gland during the peripubertal period, suggesting alterations to the peripubertal hormone response. We now investigate whether perinatal exposure to these compounds alters the gene expression profiles of the developing glands to identify the dysregulated signaling pathways and the underlying mechanisms. G, V, or GV (1 mg/kg body weight per day) was added to diet of Wistar rats, from conception to weaning; female offspring mammary glands were collected at postnatal days (PNDs) 35 and 50. Genes displaying differential expression and belonging to different functional categories were validated by quantitative PCR and immunocytochemistry. At PND35, G had little effect; the slight changes noted were in genes related to morphogenesis. The changes following exposure to V concerned the functional categories associated with development (Cldn1, Krt17, and Sprr1a), carbohydrate metabolism, and steroidogenesis. The GV mixture upregulated genes (Krt17, Pvalb, and Tnni2) involved in muscle development, indicating effects on myoepithelial cells during mammary gland morphogenesis. Importantly, at PND50, cycling females exposed to GV showed an increase in the expression of genes (Csn2, Wap, and Elf5) related to differentiation, consistent with the previously reported abnormal lobuloalveolar development previously described. Thus, perinatal exposure to GV alters the mammary gland hormone response differently at PND35 (puberty) and in animals with established cycles.
Schwartz Joel L
Full Text Available Abstract Background The head and neck/oral squamous cell carcinoma (HNOSCC is a diverse group of cancers, which develop from many different anatomic sites and are associated with different risk factors and genetic characteristics. The oral tongue squamous cell carcinoma (OTSCC is one of the most common types of HNOSCC. It is significantly more aggressive than other forms of HNOSCC, in terms of local invasion and spread. In this study, we aim to identify specific transcriptomic signatures that associated with OTSCC. Results Genome-wide transcriptomic profiles were obtained for 53 primary OTSCCs and 22 matching normal tissues. Genes that exhibit statistically significant differences in expression between OTSCCs and normal were identified. These include up-regulated genes (MMP1, MMP10, MMP3, MMP12, PTHLH, INHBA, LAMC2, IL8, KRT17, COL1A2, IFI6, ISG15, PLAU, GREM1, MMP9, IFI44, CXCL1, and down-regulated genes (KRT4, MAL, CRNN, SCEL, CRISP3, SPINK5, CLCA4, ADH1B, P11, TGM3, RHCG, PPP1R3C, CEACAM7, HPGD, CFD, ABCA8, CLU, CYP3A5. The expressional difference of IL8 and MMP9 were further validated by real-time quantitative RT-PCR and immunohistochemistry. The Gene Ontology analysis suggested a number of altered biological processes in OTSCCs, including enhancements in phosphate transport, collagen catabolism, I-kappaB kinase/NF-kappaB signaling cascade, extracellular matrix organization and biogenesis, chemotaxis, as well as suppressions of superoxide release, hydrogen peroxide metabolism, cellular response to hydrogen peroxide, keratinization, and keratinocyte differentiation in OTSCCs. Conclusion In summary, our study provided a transcriptomic signature for OTSCC that may lead to a diagnosis or screen tool and provide the foundation for further functional validation of these specific candidate genes for OTSCC.
Xiao, Yuan; Yuan, Wentao; Yu, Bo; Guo, Yan; Xu, Xu; Wang, Xinqiong; Yu, Yi; Yu, Yi; Gong, Biao; Xu, Chundi
To identify causal mutations in certain genes in children with acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP). After patients were enrolled (CP, 55; ARP, 14) and their clinical characteristics were investigated, we performed next-generation sequencing to detect nucleotide variations among the following 10 genes: cationic trypsinogen protease serine 1 (PRSS1), serine protease inhibitor, Kazal type 1 (SPINK1), cystic fibrosis transmembrane conductance regulator gene (CFTR), chymotrypsin C (CTRC), calcium-sensing receptor (CASR), cathepsin B (CTSB), keratin 8 (KRT8), CLAUDIN 2 (CLDN2), carboxypeptidase A1 (CPA1), and ATPase type 8B member 1 (ATP8B1). Mutations were searched against online databases to obtain information on the cause of the diseases. Certain novel mutations were analyzed using the SIFT2 and Polyphen-2 to predict the effect on protein function. There were 45 patients with CP and 10 patients with ARP who harbored 1 or more mutations in these genes; 45 patients had at least 1 mutation related to pancreatitis. Mutations were observed in the PRSS1, SPINK1, and CFTR genes in 17 patients, the CASR gene in 5 patients, and the CTSB, CTRC, and KRT8 genes in 1 patient. Mutations were not found in the CLDN, CPA1, or ATP8B1 genes. We found that mutations in SPINK1 may increase the risk of pancreatic duct stones (OR, 11.07; P = .003). The patients with CFTR mutations had a higher level of serum amylase (316.0 U/L vs 92.5 U/L; P = .026). Mutations, especially those in PRSS1, SPINK1, and CFTR, accounted for the major etiologies in Chinese children with CP or ARP. Children presenting mutations in the SPINK1 gene may have a higher risk of developing pancreatic duct stones. Copyright © 2017 Elsevier Inc. All rights reserved.
Szczecinska, W; Nesteruk, D; Wertheim-Tysarowska, K; Greenblatt, D T; Baty, D; Browne, F; Liu, L; Ozoemena, L; Terron-Kwiatkowski, A; McGrath, J A; Mellerio, J E; Morton, J; Woźniak, K; Kowalewski, C; Has, C; Moss, C
Acral peeling skin syndrome (APSS) is a rare skin fragility disorder usually caused by mutations in the transglutaminase 5 gene (TGM5). We investigated the mutation spectrum of APSS in the U.K., Germany and Poland. We identified 59 children with APSS from 52 families. The phenotype was readily recognizable, with some variation in severity both within and between families. Most cases had been misdiagnosed as the localized form of epidermolysis bullosa simplex (EBS-loc). Eighteen different TGM5 mutations were identified, 15 of which were novel. Eight mutations were unique to a single family, nine each occurred in two families, while the common p.Gly113Cys mutation linked to a second missense variant p.Thr109Met occurred in 47 of the 52 families and was homozygous in 28. Most patients were of nonconsanguineous white European origin. We propose that APSS is under-reported and widely misdiagnosed as EBS-loc, with significant counselling implications as APSS is autosomal recessive while EBS-loc is dominant. We recommend screening for TGM5 mutations when EBS-loc is suspected but not confirmed by mutations in KRT5 or KRT14. Our report trebles the number of known TGM5 mutations. It provides further evidence that p.Gly113Cys is a founder mutation in the European population. This is consistent with the striking ethnic distribution of APSS in U.K., where the majority of patients are of nonconsanguineous white European origin, in contrast to the pattern of other recessive skin disorders. © 2014 British Association of Dermatologists.
Lallemant, Benjamin; Hollande, Frédéric; Lallemant, Jean-Gabriel; Lumbroso, Serge; Brouillet, Jean-Paul; Evrard, Alexandre; Combescure, Christophe; Chapuis, Heliette; Chambon, Guillaume; Raynal, Caroline; Reynaud, Christophe; Sabra, Omar; Joubert, Dominique
Analysis of 23 published transcriptome studies allowed us to identify nine genes displaying frequent alterations in HNSCC (FN1, MMP1, PLAU, SPARC, IL1RN, KRT4, KRT13, MAL, and TGM3). We aimed to independently confirm these dysregulations and to identify potential relationships with clinical data for diagnostic, staging and prognostic purposes either at the tissue level or in saliva rinse. For a period of two years, we systematically collected tumor tissue, normal matched mucosa and saliva of patients diagnosed with primary untreated HNSCC. Expression levels of the nine genes of interest were measured by RT-qPCR in tumor and healthy matched mucosa from 46 patients. MMP1 expression level was measured by RT-qPCR in the salivary rinse of 51 HNSCC patients and 18 control cases. Dysregulation of the nine genes was confirmed by the Wilcoxon test. IL1RN, MAL and MMP1 were the most efficient diagnostic markers of HNSCC, with ROC AUC > 0.95 and both sensitivity and specificity above 91%. No clinically relevant correlation was found between gene expression level in tumor and T stage, N stage, tumor grade, global survival or disease-free survival. Our preliminary results suggests that with 100% specificity, MMP1 detection in saliva rinse is potentially useful for non invasive diagnosis of HNSCC of the oral cavity or oropharynx, but technical improvement is needed since sensitivity was only 20%. IL1RN, MAL and MMP1 are prospective tumor diagnostic markers for HNSCC. MMP1 overexpression is the most promising marker, and its detection could help identify tumor cells in tissue or saliva
Mannsåker, Bård; Vikan, Torkel; Holme, Jonas
There is some evidence linking air pollution to cardiovascular morbidity. Our aim was to examine whether there is a correlation between air pollution and cardiovascular morbidity in the city of Trondheim, Norway. We compared the mean daily number of admissions for cardiovascular disease to the St. Olav University hospital on days with relatively low and high levels of PM10 (1993-2001), PM2,5, NO, NO2, SO2, O3, toluene and paraxylene (1998-2001). A time series analysis was carried out to see how day-to-day variations in concentrations of air pollutants correlated with the number of hospitalizations for cardiovascular disease. In the bivariate analysis, the mean daily number of hospitalizations was found to be significantly higher (p < 0.05) on days with NO and NO2 levels above the 80 th percentile (57.6 microg/m3 and 43.1 microg/m3, respectively) than on days with pollutant levels below the 20th percentile (11.3 microg/m3 and 16.9 microg/m3, respectively). Time series analysis did not show any statistically significant correlation between day-to-day variations in air pollution and hospital admissions for cardiovascular disease. The findings regarding NO2 and NO indicate that exposure to gases and/or ultra-small particles from diesel exhaust may influence cardiovascular morbidity.
Full Text Available Lars H Pedersen,1,2 Olav B Petersen,1,2 Mette Nørgaard,3 Charlotte Ekelund,4 Lars Pedersen,3 Ann Tabor,4 Henrik T Sørensen3 1Department of Clinical Medicine, Aarhus University, 2Department of Obstetrics and Gynecology, 3Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, 4Department of Fetal Medicine, Rigshospitalet, Copenhagen, Denmark Abstract: A linked population-based database is being created in Denmark for research on drug safety during pregnancy. It combines information from the Danish National Health Service Prescription Database (with information on all prescriptions reimbursed in Denmark since 2004, the Danish Fetal Medicine Database, the Danish National Registry of Patients, and the Medical Birth Registry. The new linked database will provide validated information on malformations diagnosed both prenatally and postnatally. The cohort from 2008 to 2014 will comprise 589,000 pregnancies with information on 424,000 pregnancies resulting in live-born children, ~420,000 pregnancies undergoing prenatal ultrasound scans, 65,000 miscarriages, and 92,000 terminations. It will be updated yearly with information on ~80,000 pregnancies. The cohort will enable identification of drug exposures associated with severe malformations, not only based on malformations diagnosed after birth but also including those having led to termination of pregnancy or miscarriage. Such combined data will provide a unique source of information for research on the safety of medications used during pregnancy. Keywords: malformations, teratology, therapeutic drug monitoring, epidemiological methods, registries
Background Overweight, obesity and associated conditions are major public health concerns in Norway. The prevalence of overweight and obesity in the general population in Norway is increasing, but there are limited data on how the situation is in hospitals. This study aimed to find the prevalence of overweight and obesity, and explore the associations of overweight, obesity and its related medical conditions in an adult in-patient sample at specified somatic and psychiatric departments at St. Olavs Hospital, Trondheim. Results A total of 497 patients participated. The mean BMI for the total sample at screening was 25.4 kg/m2. The prevalence of overweight and obesity was 45.1%. There was a higher association of overweight and obesity among patients aged 40–59 years (OR: 1.7) compared to those being younger. There was no significant difference between the somatic and the psychiatric samples. In the somatic sample overweight and obesity was associated with obesity-related conditions for both genders (OR: 2.0 and 2.1, respectively), when adjusted for age. Conclusion The substantial prevalence of overweight and obese patients may pose a threat to future hospital services. To further address the burden of overweight and obesity in hospitals, we need more knowledge about consequences of length of stay, use of resources and overall cost. PMID:24571809
Rekand, T; Schaanning, E E; Varga, V; Schattel, U; Gronning, M
A national retrospective descriptive study. To study the clinical effects of spinal cord injuries (SCIs) caused by paragliding accidents in Norway. Spinal cord units at Haukeland University Hospital, Sunnaas Rehabilitation Hospital and St Olav Hospital in Norway. We studied the medical files for nine patients with SCI caused by paragliding accidents to evaluate the circumstances of the accidents, and clinical effects of injury. We obtained the data from hospital patient files at all three spinal units in Norway and crosschecked them through the Norwegian Paragliding Association's voluntary registry for injuries. All patients were hospitalized from 1997 to 2006, eight men and one woman, with mean age 30.7 years. The causes of the accidents were landing problems combined with unexpected wind whirls, technical problems and limited experience with unexpected events. All patients contracted fractures in the thoracolumbal junction of the spine, most commonly at the L1 level. At clinical follow-up, all patients presented clinically incomplete SCI (American Spinal Injury Association impairment scores B-D). Their main health problems differed widely, ranging from urinary and sexual disturbances to neuropathic pain and loss of motor functioning. Only three patients returned to full-time employment after rehabilitation. Paragliding accidents cause spinal fractures predominantly in the thoracolumbal junction with subsequent SCIs and increased morbidity. All patients experienced permanent health problems that influenced daily activities and required long-time clinical follow-up and medical intervention. Better education in landing techniques and understanding of aerodynamics may reduce the risk of paragliding accidents.
Full Text Available Ottar SjaastadDepartment of Neurology, St. Olav´s Hospital, 7006 Trondheim University Hospitals, Trondheim, NorwayAbstract: Shortlasting, unilateral, neuralgiform headache attacks with conjunctival injection and tearing (SUNCT syndrome is a rare headache, described by our group in 1989. This overview presents our early studies of SUNCT pathogenesis. Due to the conspicuous ictal, ocular phenomena, ie, conjunctival injection and tearing, our studies started out with ocular parameters: intraocular pressure and corneal indentation pulse amplitudes, both of which showed clear ictal increments, symptomatic side. Beat-to-beat, noninvasive blood pressure measurements during attack showed instant, systolic blood pressure rise and corresponding pulse rate decrease. Carotid body, the principal peripheral chemoreceptor, seemed to function normally. The middle cerebral artery was dilated during attacks, particularly on the symptomatic side. Finally, some viewpoints are added regarding terminology. SUNCT is a workable and accepted term. There does not seem to be any need for another, fictitious term to describe the same clinical picture.Keywords: SUNCT syndrome, intraocular blood flow, intraocular pressure, median artery blood flow, carotid body function, hypothalamic stimulation
From the beginning of October this year the United Nations Postal Administration has been able to issue Swiss-denomination stamps valid for correspondence posted at the Palais des Nations, Geneva. This is the first time that the UN in Geneva has been able to send mail using its own postage stamps and is therefore of great interest to philatelists. The principal aim of the UN Postal Administration is to make UN activities and those of the specialized agencies better known in the world through stamps. In 1969 there have been issues in honour of the UN Institute for Training and Research (UNITAR), the Economic Commission for Latin America, the International Law Commission and the International Labour Organisation (ILO). Among those next year will be a stamp to commemorate the efforts of the World Health Organization (WHO) to fight cancer. There are eight denominations in the new Swiss issue, each with special designs. They are 1 franc (designed by Rashid-ud-Din, Pakistan); 10 centimes, 30 centimes and 75 centime (Ole Hamann, Denmark); 5 centimes (Jozsef Vertel, Hungary); 3 francs, showing the statue in the Trusteeship Council Chamber, New York; 50 centimes (Olav S. Mathiesen, Denmark); and 20 centimes (Georges Hamori, Australia). (author)
Beyer-Olsen, E M; Risnes, S
An excavation in Trondheim, Norway, in 1984-85, uncovered a part of the medieval (1100-1600) cemetery of St Olav's Church. Of 388 excavated skeletons, 248 had skulls where the condition of the jaws and teeth allowed examination. In 51 of these skulls the teeth exhibited a characteristic blackish staining. A higher percentage of affected skulls was found in areas with organic, woodchip layers than in areas with gravelly sand. Affected skulls tended to have a high percentage of their teeth stained, but the staining tended to be restricted to only one or two of the three tooth surfaces scored. Posterior teeth were more often affected than anterior teeth, the occlusal/incisal part more often than the cervical part, and the buccal/labial part more often than the lingual part. Nonerupted third molars could also be stained. Staining seemed to be hampered by calculus. Occurrence of staining was independent of the presence or absence of a coffin and of coffin type. The extent of staining (% of stained surfaces within a dentition) was independent of sex and age. High correlation was found between all four jaw quadrants. There was no independence between color of the jawbone and occurrence of stained teeth. It was concluded that the staining phenomenon probably can be ascribed to factors in the soil. In vivo predisposing influences cannot be excluded.
Pape, K; Westin, S
When Trondheim celebrated its millenium in 1997, this also marked a 1000 year-old medical tradition. In medieval times, sick and disabled people made their pilgrimage to the Nidaros cathedral and the grave of Saint Olav (995-1030). Working from the assumption that every organized society develops rituals and rules to deal with disease and death, we have looked for evidence of what kind of healers one would expect there were in medieval Trondheim up to the reformation in 1537. Sources include reports from archaeological excavations, written material of both medieval and more recent origin, buildings and objects, and living traditions. Three kinds of healer traditions can be identified: The popular and "wise" folk healers were based on traditional pre-Christian mythology and belief in natural forces. The charitable clerics emerged with Christianity. The "professional" wound healers evolved from the needs of the military, later to merge with the early barber surgeons. Traces of scientific traditions, the Salerno school and early European university medicine can be found in local texts, but there is no evidence of any university educated doctor practising in Trondheim before the 17th century.
Full Text Available Olle Söderhamn1,2, John Olav Bjørnestad1, Anne Skisland1, Christina Cliffordson21Faculty of Health and Sport Sciences, University of Agder, Grimstad and Kristiansand, Norway; 2Department of Nursing, Health and Culture, University West, Trollhättan, SwedenAbstract: The aim of this study was to investigate the construct validity of the Moral Development Scale for Professionals (MDSP using structural equation modeling. The instrument is a 12-item self-report instrument, developed in the Scandinavian cultural context and based on Kohlberg’s theory. A hypothesized simplex structure model underlying the MDSP was tested through structural equation modeling. Validity was also tested as the proportion of respondents older than 20 years that reached the highest moral level, which according to the theory should be small. A convenience sample of 339 nursing students with a mean age of 25.3 years participated. Results confirmed the simplex model structure, indicating that MDSP reflects a moral construct empirically organized from low to high. A minority of respondents >20 years of age (13.5% scored more than 80% on the highest moral level. The findings support the construct validity of the MDSP and the stages and levels in Kohlberg’s theory.Keywords: Kohlberg, scale testing, simplex structure model, structural equation modeling
Nysted, M; Drogset, J O
To describe the mechanism, location and types of injury for all patients treated for trampoline-associated injuries at St Olav's University Hospital, Trondheim, Norway, from March 2001to October 2004. Patients were identified from a National Injury Surveillance System. All patients were asked to complete a standard questionnaire at their first visit at the hospital. Most data were recorded prospectively, but data on the mechanism of injury, the number of participants on the trampoline at the time of injury, adult supervision and whether the activity occurred at school or in another organised setting were collected retrospectively. A total of 556 patients, 56% male and 44% female, were included. The mean age of patients was 11 (range 1-62) years. 77% of the injuries occurred on the body of the trampoline, including falls on to the mat, collisions with another jumper, falls on to the frame or the springs, and performing a somersault, whereas 22% of the people fell off the trampoline. In 74% of the cases, more than two people were on the trampoline, with as many as nine trampolinists noted at the time of injury. For children Trampolining can cause serious injuries, especially in the neck and elbow areas of young children. The use of a trampoline is a high-risk activity. However, a ban is not supported. The importance of having safety guidelines for the use of trampolines is emphasised.
Hansen, Hanne Hoff; Hasselgård, Cecilie Edh; Undheim, Anne Mari; Indredavik, Marit Sæbø
Few studies have focused the association between bullying and psychiatric disorders in clinical samples. The aim of this study was to examine if bullying behaviour was associated with psychiatric disorders and school well-being. The cross-sectional study was part of a health survey at St. Olav's University Hospital. The sample consisted of 685 adolescent patients aged 13-18 years who completed an electronic questionnaire. Clinical diagnoses were collected from clinical records. In this clinical psychiatric sample, 19% reported being bullied often or very often, and 51% reported being bullied from time to time. Logistic regression analyses showed associations between being a victim and having a mood disorder, and between being involved in bullying behaviour and reporting lower scores on school well-being. No difference was found in bullying behaviour on gender, age and SES. The risk of being a victim was high among adolescents in this clinical sample, especially among patients with mood disorders. Any involvement in bullying behaviour was associated with reduced school well-being.
Full Text Available Identification of zygosity in transgenik fish is normally achieved by PCR analysis with genomic DNA template extracted from the tissue of progenies which are derived by mating the transgenic fish and wild-type counterpart. This method needs relatively large amounts of fish material and is time- and labor-intensive. New approaches addressing this problem could be of great help for fish biotechnologists. In this experiment, we applied a quantitative real-time PCR (qr-PCR method to analyze zygosity in a stable line of transgenic zebrafish (Danio rerio carrying masu salmon, Oncorhynchus masou D6-desaturase-like gene. The qr-PCR was performed using iQ SYBR Green Supermix in the iCycler iQ Real-time PCR Detection System (Bio-Rad Laboratories, USA. Data were analyzed using the comparative cycle threshold method. The results demonstrated a clear-cut identification of all transgenic fish (n=20 classified as a homozygous or heterozygous. Mating of those fish with wild-type had revealed transgene transmission to the offspring following expected Mendelian laws. Thus, we found that the qTR-PCR to be effective for a rapid and precise determination of zygosity in transgenic fish. This technique could be useful in the establishment of breeding programs for mass transgenic fish production and in experiments in which zygosity effect could have a functional impact. Keywords: quantitative real-time PCR; zygosity; transgenic fish; mass production ABSTRAK Identifikasi sigositas ikan transgenik biasanya dilakukan menggunakan analisa PCR dengan cetakan DNA genomik yang diekstraksi dari jaringan ikan hasil persilangan antara ikan transgenik dan ikan normal. Metode ini memerlukan ikan dalam jumlah yang banyak, dan juga waktu serta tenaga. Pendekatan baru untuk mengatasi masalah tersebut akan memberikan manfaat besar kepada peneliti bioteknologi perikanan. Pada penelitian ini, kami menggunakan metode PCR real-time kuantitatif (krt-PCR untuk
Kravik Katherine L
periods and a recovery time of 22 days. Mitotic activity ceased in response to drug treatment for all cell lines, consistent with down-regulation of mitosis-regulatory genes. Differential expression in response to 5-FU treatment was demonstrated for genes involved in regulation of nucleotide binding/metabolism (ATAD2, GNL2, GNL3, MATR3, amino acid metabolism (AHCY, GSS, IVD, OAT, cytoskeleton organization (KRT7, KRT8, KRT19, MAST1, transport (MTCH1, NCBP1, SNAPAP, VPS52, and oxygen metabolism (COX5A, COX7C. Conclusion Our gene expression data suggest that altered regulation of nucleotide metabolism, amino acid metabolism, cytoskeleton organization, transport, and oxygen metabolism may underlie the differential resistance to 5-FU seen in these cell lines. The contributory roles to 5-FU resistance of some of the affected genes on these pathways will be assessed in future studies.
Despite a substantial increase in hospital resources, increased hospital admissions and out-patient visits, long waiting lists have been a significant problem in Norwegian health care. A detailed analysis of the development in resource allocation and productivity at St. Olavs University Hospital in central Norway was therefore undertaken. Resource allocation and patient volume was analysed during the period 1995 to 2001. Data were analysed both for emergency and elective admissions as well as outpatient visits specified into new referrals and follow-up consultations. Full time employee equivalents for doctors and nurses increased by 36.6% and 25.9%, respectively, and all employees by 28.1%. However, admitted patients, outpatient consultations and surgical procedures only increased by 10%, 15% and 8.3%, respectively. Thus, the productivity for each hospital employee, defined as operations pr. surgeon, outpatient consultations pr. doctor etc. was significantly reduced. A striking finding was that although the number of outpatient consultations increased, the number of new referrals actually went down and the whole increase in activity at the outpatient clinics could be explained by a substantial increase in follow-up consultations. This trend was more evident in the surgical departments, where some departments actually showed a reduction in total outpatient consultations. In view of the slow increase in hospital activity in spite of a significant increase in resources, it can be speculated that patient volume might be a limiting factor for hospital activity. The health market (patient population) might not be big enough in relation to the investments in increased production capacity (equipment and manpower).
Aune, Ingvild; Möller, Anders
To increase our understanding of how pregnant women experience early ultrasound examination that includes a risk assessment for chromosomal anomalies and how such women perceive the test results. Qualitative study at St. Olavs Hospital in Norway. Both pre- and post-examination interviews were conducted with ten pregnant women who underwent risk assessment for chromosomal anomalies. Grounded theory was used to analyse the results. The study generated a core category (I want a choice, but I don't want to decide), which related to the conflict between choice and decision making. There were also five main categories (existential choices, search for knowledge, anxiety, feeling of guilt and counselling and care). The main categories describe the complex feelings experienced by the women regarding the risk assessment. Factors contributing to the difficulty of choice included loss of control and coping, emotional connection to the fetus and social pressure. As the women sought independent choices without any external influence, they also felt greater responsibility. The women's understanding of the actual risk varied, and they used different types of logic and methods to evaluate the risk and reach a decision. The pregnant women in this study wanted prenatal diagnostic information and easy access to specialty services. Stress-related feelings and non-transparent information about the actual and perceived risks as well as personal moral judgments made the decision-making process complicated. Improved distribution of information and frequent contact with health professionals may help such women to make informed choices in accordance with their values and beliefs. Copyright © 2010 Elsevier Ltd. All rights reserved.
Wasmuth, H H; Tranø, G; Wibe, A; Endreseth, B H; Rydning, A; Myrvold, H E
The long-term failure rate of ileal pouch-anal anastomosis (IPAA) is 10-15%. When salvage surgery is unsuccessful, most surgeons prefer pouch excision with conventional ileostomy, thus sacrificing 40-50 cm of ileum. Conversion of a pelvic pouch to a continent ileostomy (CI, Kock pouch) is an alternative that preserves both the ileal surface and pouch properties. The aim of the study was to evaluate clinical outcome after the construction of a CI following a failed IPAA. During 1984-2007, 317 patients were operated with IPAA at St Olavs Hospital and evaluated for failure, treatment and outcome. Seven patients with IPAA failure had CI. Four patients with IPAA failure referred from other hospitals underwent conversion to CI and are included in the final analysis. Seven patients had a CI constructed from the transposing pelvic pouch and four had the pelvic pouch removed and a new continent pouch constructed from the distal ileum. Median follow up after conversion to CI was 7 years (0-17 years). Two CI had to be removed due to fistulae. One patient needed a revision of the nipple valve due to pouch loosening. At the end of follow-up, 8 of the 11 patients were fully continent. One patient with Crohn's disease had minor leakage. In patients with pelvic pouch failure, the possibility of conversion to CI should be presented to the patient as an alternative to pouch excision and permanent ileostomy. The advantage is the continence and possibly a better body image. Construction of a CI on a new ileal segment may be considered, but the consequences of additional small bowel loss and risk of malnutrition if the Kock pouch fails should be appraised.
Stein Kaasa, MD, speaks to Dominic Chamberlain, Assistant Commissioning Editor: Stein Kaasa specializes in oncology and palliative medicine. In 1993 he was appointed as the first professor in palliative medicine in Scandinavia and he was one of the founders of the palliative care unit in Trondheim (Norway). He also was the founder of the European Palliative Care Research Centre. He has been president of the European Association for Palliative Care, coordinator for one EU-funded project and is Work Package Leader of several EU-funded research collaboratives and international partnerships on research and policy development. Kaasa has been an important advocate for evidence-based practice and has worked extensively to get palliative care research on the agenda, both nationally and internationally. Through his role as Cancer Director in Norway he coordinated and led the development of guidelines for different cancer diseases. Important areas of work were the development of regional cancer treatment guidelines and integration of patient disease trajectories into the existing guidelines. Currently he is Vice Managing Director at St Olavs Hospital, Trondheim University Hospital (Norway), Professor of palliative medicine at the Faculty of Medicine, Norwegian University of Science and Technology and leads the European Palliative Care Research Centre and chairs the European Association for Palliative Care Research Network. Professor Kaasa has published more than 450 articles and book chapters. He has authored the Nordic Textbook of Palliative Care and is coauthor and editor of the Oxford Textbook of Palliative Medicine. Professor Kaasa advises many international journals - either as an advisory board member or as a reviewer (Journal of Pain and Symptom Management, Palliative Medicine, Journal of Palliative Medicine, Oncology, Journal of Clinical Oncology, Pain and The Lancet Oncology).
Full Text Available Borge Lillebo,1 Andreas Seim,2 Ole-Petter Vinjevoll,3 Oddvar Uleberg31Norwegian EHR Research Centre, Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway; 2Department of Computer and Information Science, Faculty of Information Technology, Mathematics and Electrical Engineering, NTNU, Trondheim, Norway; 3Department of Anaesthesia and Emergency Medicine, St Olav's University Hospital, Trondheim, NorwayBackground: Trauma teams improve the initial management of trauma patients. Optimal timing of trauma alerts could improve team preparedness and performance while also limiting adverse ripple effects throughout the hospital. The purpose of this study was to evaluate how timing of trauma team activation and notification affects initial in-hospital management of trauma patients.Methods: Data from a single hospital trauma care quality registry were matched with data from a trauma team alert log. The time from patient arrival to chest X-ray, and the emergency department length of stay were compared with the timing of trauma team activations and whether or not trauma team members received a preactivation notification.Results: In 2009, the trauma team was activated 352 times; 269 times met the inclusion criteria. There were statistically significant differences in time to chest X-ray for differently timed trauma team activations (P = 0.003. Median time to chest X-ray for teams activated 15–20 minutes prearrival was 5 minutes, and 8 minutes for teams activated <5 minutes before patient arrival. Timing had no effect on length of stay in the emergency department (P = 0.694. We found no effect of preactivation notification on time to chest X-ray (P = 0.474 or length of stay (P = 0.684.Conclusion: Proactive trauma team activation improved the initial management of trauma patients. Trauma teams should be activated prior to patient arrival.Keywords: emergency medical service communication systems
Full Text Available Knut Magne Augestad,1–3 Arthur Revhaug,1,3 Roar Johnsen,4 Stein-Olav Skrøvseth,2 Rolv-Ole Lindsetmo1,3 1Department of Gastrointestinal Surgery, 2Department of Integrated Care and Telemedicine, University Hospital North Norway, Tromsø, Norway; 3Department of Colorectal Surgery, University Hospitals Case Medical Center, Cleveland, Ohio, USA; 4Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway Background: Poor coordination between levels of care plays a central role in determining the quality and cost of health care. To improve patient coordination, systematic structures, guidelines, and processes for creating, transferring, and recognizing information are needed to facilitate referral routines. Methods: Prospective observational survey of implementation of electronic medical record (EMR-supported guidelines for surgical treatment. Results: One university clinic, two local hospitals, 31 municipalities, and three EMR vendors participated in the implementation project. Surgical referral guidelines were developed using the Delphi method; 22 surgeons and seven general practitioners (GPs needed 109 hours to reach consensus. Based on consensus guidelines, an electronic referral service supported by a clinical decision support system, fully integrated into the GPs' EMR, was developed. Fifty-five information technology personnel and 563 hours were needed (total cost 67,000 £ to implement a guideline supported system in the EMR for 139 GPs. Economical analyses from a hospital and societal perspective, showed that 504 (range 401–670 and 37 (range 29–49 referred patients, respectively, were needed to provide a cost-effective service. Conclusion: A considerable amount of resources were needed to reach consensus on the surgical referral guidelines. A structured approach by the Delphi method and close collaboration between IT personnel, surgeons and primary care physicians were needed to
Full Text Available Abstract Background Hip fractures in older people are associated with high morbidity, mortality, disability and reduction in quality of life. Traditionally people with hip fracture are cared for in orthopaedic departments without additional geriatric assessment. However, studies of postoperative rehabilitation indicate improved efficiency of multidisciplinary geriatric rehabilitation as compared to traditional care. This randomized controlled trial (RCT aims to investigate whether an additional comprehensive geriatric assessment of hip fracture patients in a special orthogeriatric unit during the acute in-hospital phase may improve outcomes as compared to treatment as usual in an orthopaedic unit. Methods/design The intervention of interest, a comprehensive geriatric assessment is compared with traditional care in an orthopaedic ward. The study includes 401 home-dwelling older persons >70 years of age, previously able to walk 10 meters and now treated for hip fracture at St. Olav Hospital, Trondheim, Norway. The participants are enrolled and randomised during the stay in the Emergency Department. Primary outcome measure is mobility measured by the Short Physical Performance Battery (SPPB at 4 months after surgery. Secondary outcomes measured at 1, 4 and 12 months postoperatively are place of residence, activities of daily living, balance and gait, falls and fear of falling, quality of life and depressive symptoms, as well as use of health care resources and survival. Discussion We believe that the design of the study, the randomisation procedure and outcome measurements will be of sufficient strength and quality to evaluate the impact of comprehensive geriatric assessment on mobility and other relevant outcomes in hip fracture patients. Trials registration ClinicalTrials.gov, NCT00667914
Betten, Jan; Roness, Aleksander Kirkerud; Endreseth, Birger Henning; Trønnes, Håkon; Tyvold, Stig Sverre; Klepstad, Pål; Nordseth, Trond
Admittance to a high dependency unit (HDU) is expensive. Patients who receive surgical treatment with 'low anterior resection of the rectum' (LAR) or 'abdominoperineal resection of the rectum' (APR) at our hospital are routinely treated in an HDU the first 16-24 h of the postoperative (PO) period. The aim of this study was to describe the extent of HDU-specific interventions given. We included patients treated with LAR or APR at the St. Olav University Hospital (Trondheim, Norway) over a 1-year period. Physiologic data and HDU-interventions recorded during the PO-period were obtained from the anesthesia information management system (AIMS). HDU-specific interventions were defined as the need for respiratory support, fluid replacement therapy >500 ml/h, vasoactive medications, or a need for high dose opioids (morphine >7.5 mg/h i.v.). Sixty-two patients were included. Most patients needed HDU-specific interventions during the first 6 h of the PO period. After this, one-third of the patients needed one or more of the HDU-specific interventions for shorter periods of time. Another one-third of the patients had a need for HDU-specific therapies for more than ten consecutive hours, primarily an infusion of nor-epinephrine. Most patients treated with LAR or APR was in need of an HDU-specific intervention during the first 6 h of the PO-period, with a marked decline after this time period. The applied methodology, using an AIMS, demonstrates that there is great variability in individual patients' postoperative needs after major surgery, and that these needs are dynamic in their nature.
Tørhaug, T; Brurok, B; Hoff, J; Helgerud, J; Leivseth, G
To assess the effect from maximal bench press strength training (MST) on wheelchair propulsion work economy (WE). Pretest-posttest case-control group design. St Olavs Hospital, Trondheim, Norway. Seventeen male individuals with spinal cord injury (SCI) paraplegia were allocated to either MST bench press (n=11) or the control group (CG) (n=7). The MST group trained bench press three times per week, for 6 weeks, starting at 85-95% of their pretest bench press one-repetition maximum (1RM). For calculation of WE during wheelchair propulsion, oxygen uptake (VO 2 ) measurements were collected during wheelchair ergometry (WCE) at submaximal workload of 50 W. Similarly, peak oxygen uptake (VO 2peak ) and peak power output (W) were measured during WCE. Individuals in the MST regimen significantly improved WE compared with the CG by 17.3 % (mean between-group differences: 95% confidence interval) of 2.63 ml kg -1 min -1 : (-4.34, -0.91) (P=0.007). Between pretest and posttest, the increase in bench press 1RM was by 17% higher in the MST group compared with the CG. At peak testing, the MST group generated significantly higher peak power compared with the CG. All other physiological variables were comparable within and between groups. A 6-week MST bench press regimen significantly improved WE during wheelchair propulsion at 50 W workload. These preliminary data support a possible beneficial role for MST to reduce the energy cost of wheelchair propulsion for SCI individuals.
Full Text Available The summer activities in the 1995/1996 austral summer of the 37th Japanese Antarctic Research Expedition (JARE-37 are reported. The JARE-37 consisted of 16 members of the summer party, one news reporter and one graduate student. The Antarctic research vessel, SHIRASE, left Tokyo on 14th November 1995 and arrived at Fremantle, West Australia on 28th November. She reached the pack ice edge near Lutzow-Holm Bay on 14th December and anchored at Syowa Station on 24th December. Transportation of cargo by helicopter to Syowa Station and to the transport point (S16 for Dome Fuji Station was carried out between 16th December 1995 and 9th January 1996. A total of 1069.5 tons of cargo, including light oil transported by pipe and freight by oversnow vehicles, were transported. Construction to replace old buildings and facilities at Syowa Station were carried out. Main construction, a building for storage, continued throughout the summer at Syowa Station. In addition, an emergency power house and a seismographic hut were built, and the old power house was torn down. Summer research programs included a marine physical survey, atmospheric work, and field surveys in ice-free areas along the Soya Coast. All of the summer party left Syowa Station on 12th February and headed to Sydney, East Australia. En route, a geodesic survey, geological and biological research were carried out at ice-free areas along the Prince Olav Coast and oceanographic, marine biological observations, geomagnetism and other work were carried out on board. Members of the summer party of JARE-37 returned to Narita by air on 27th March 1996.
Full Text Available Jannike Kaasbøll,1 Stian Lydersen,1 Marit S Indredavik1,2 1Regional Centre for Child and Youth Mental Health and Child Welfare of Central Norway, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway; 2Department of Child and Adolescent Psychiatry, St Olav's Hospital, Trondheim University Hospital Trondheim, Norway Purpose: The aim of the present study was to investigate possible associations between parental chronic pain and smoking, alcohol, and drug use in adolescent offspring. Methods: Cross-sectional data from Nord-Trøndelag Health Study (HUNT 3, a Norwegian population-based health survey conducted in the period 2006–2008 was utilized. The present sample consisted of adolescents aged 13–18 years (n=3,227 for whom information was available on maternal and paternal health statuses. Results: Results from multivariable ordinal and binary logistic regression analyses, adjusting for potential confounding factors (child age, parental age, education, and organ specific illness indicated that the estimated odds ratios (OR for smoking (OR =1.72, 95% confidence interval [CI] [1.00, 3.05], P=0.049 and alcohol intoxication (drunkenness (OR =1.56, 95% CI [1.05, 2.33], P=0.029 were higher for boys whose mother and father had chronic pain, compared with boys for whom neither parent had chronic pain. These associations were slightly attenuated by additional adjustment for pain-related factors, such as parental smoking and symptoms of anxiety and depression. Parental chronic pain was not significantly associated with girls' levels of substance use. There were significant interaction effects between parental chronic pain and child sex on offspring's alcohol and smoking. Conclusion: The present study expands on existing knowledge and provides groundwork for preventive and specific measures targeting substance use in families burdened with parental chronic pain. Keywords: adolescents, chronic pain, smoking, alcohol, drugs
Full Text Available Charlotte Kvist Ekelund,1 Tine Iskov Kopp,2 Ann Tabor,1 Olav Bjørn Petersen3 1Department of Obstetrics, Center of Fetal Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; 2Registry Support Centre (East – Epidemiology and Biostatistics, Research Centre for Prevention and Health, Glostrup, Denmark; 3Fetal Medicine Unit, Aarhus University Hospital, Aarhus Nord, Denmark Aim: The aim of this study is to set up a database in order to monitor the detection rates and false-positive rates of first-trimester screening for chromosomal abnormalities and prenatal detection rates of fetal malformations in Denmark. Study population: Pregnant women with a first or second trimester ultrasound scan performed at all public hospitals in Denmark are registered in the database. Main variables/descriptive data: Data on maternal characteristics, ultrasonic, and biochemical variables are continuously sent from the fetal medicine units' Astraia databases to the central database via web service. Information about outcome of pregnancy (miscarriage, termination, live birth, or stillbirth is received from the National Patient Register and National Birth Register and linked via the Danish unique personal registration number. Furthermore, results of all pre- and postnatal chromosome analyses are sent to the database. Conclusion: It has been possible to establish a fetal medicine database, which monitors first-trimester screening for chromosomal abnormalities and second-trimester screening for major fetal malformations with the input from already collected data. The database is valuable to assess the performance at a regional level and to compare Danish performance with international results at a national level. Keywords: prenatal screening, nuchal translucency, fetal malformations, chromosomal abnormalities
Full Text Available Prostate carcinoma (PRAD is one of the most frequently diagnosed malignancies amongst men worldwide. It is well-known that androgen receptor (AR plays a pivotal role in a vast majority of prostate tumors. However, recent evidence emerged stating that estrogen receptors (ERs may also contribute to prostate tumor development. Moreover, progression and aggressiveness of prostate cancer may be associated with differential expression genes of epithelial-to-mesenchymal transition (EMT. Therefore we aimed to assess the significance of receptors status as well as EMT marker genes expression among PRAD patients in accordance to their age and Gleason score.We analyzed TCGA gene expression profiles of 497 prostate tumor samples according to 43 genes involved in EMT and 3 hormone receptor genes (AR, ESR1, ESR2 as well as clinical characteristic of cancer patients. Then patients were divided into four groups according to their age and 5 groups according to Gleason score. Next, we evaluated PRAD samples according to relationship between the set of variables in different combinations and compared differential expression in subsequent groups of patients. The analysis was applied using R packages: FactoMineR, gplots, RColorBrewer and NMF.MFA analysis resulted in distinct grouping of PRAD patients into four age categories according to expression level of AR, ESR1 and ESR2 with the most distinct group of age less than 50 years old. Further investigations indicated opposite expression profiles of EMT markers between different age groups as well as strong association of EMT gene expression with Gleason score. We found that depending on age of prostate cancer patients and Gleason score EMT genes with distinctly altered expression are: KRT18, KRT19, MUC1 and COL4A1, CTNNB1, SNAI2, ZEB1 and MMP3.Our major observation is that prostate cancer from patients under 50 years old compared to older ones has entirely different EMT gene expression profiles showing potentially
Lipka, A; Paukszto, L; Majewska, M; Jastrzebski, J P; Myszczynski, K; Panasiewicz, G; Szafranska, B
The Eurasian beaver is one of the largest rodents that, despite its high impact on the environment, is a non-model species that lacks a reference genome. Characterising genes critical for pregnancy outcome can serve as a basis for identifying mechanisms underlying effective reproduction, which is required for the success of endangered species conservation programs. In the present study, high-throughput RNA sequencing (RNA-seq) was used to analyse global changes in the Castor fiber subplacenta transcriptome during multiple pregnancy. De novo reconstruction of the C. fiber subplacenta transcriptome was used to identify genes that were differentially expressed in placentas (n=5) from two females (in advanced twin and triple pregnancy). Analyses of the expression values revealed 124 contigs with significantly different expression; of these, 55 genes were identified using MegaBLAST. Within this group of differentially expressed genes (DEGs), 18 were upregulated and 37 were downregulated in twins. Most DEGs were associated with the following gene ontology terms: cellular process, single organism process, response to stimulus, metabolic process and biological regulation. Some genes were also assigned to the developmental process, the reproductive process or reproduction. Among this group, four genes (namely keratin 19 (Krt19) and wingless-type MMTV integration site family - member 2 (Wnt2), which were downregulated in twins, and Nik-related kinase (Nrk) and gap junction protein β2 (Gjb2), which were upregulated in twins) were assigned to placental development and nine (Krt19, Wnt2 and integrin α 7 (Itga7), downregulated in twins, and Nrk, gap junction protein β6 (Gjb6), GATA binding protein 6 (Gata6), apolipoprotein A-I (ApoA1), apolipoprotein B (ApoB) and haemoglobin subunit α 1 (HbA1), upregulated in twins) were assigned to embryo development. The results of the present study indicate that the number of fetuses affects the expression profile in the C. fiber
Wen, Li; Liu, Ye-Fang; Jiang, Cen; Zeng, Shao-Qian; Su, Yue; Wu, Wen-Jun; Liu, Xi-Yang; Wang, Jian; Liu, Ying; Su, Chen; Li, Bai-Xue; Feng, Quan-Sheng
Given the challenges in exploring lifelong therapy with little side effect for human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) cases, there is increasing interest in developing traditional Chinese medicine (TCM) treatments based on specific TCM syndrome. However, there are few objective and biological evidences for classification and diagnosis of HIV/AIDS TCM syndromes to date. In this study, iTRAQ-2DLC-MS/MS coupled with bioinformatics were firstly employed for comparative proteomic profiling of top popular TCM syndromes of HIV/AIDS: accumulation of heat-toxicity (AHT) and Yang deficiency of spleen and kidney (YDSK). It was found that for the two TCM syndromes, the identified differential expressed proteins (DEPs) as well as their biological function distributions and participation in signaling pathways were significantly different, providing biological evidence for the classification of HIV/AIDS TCM syndromes. Furthermore, the TCM syndrome-specific DEPs were confirmed as biomarkers based on western blot analyses, including FN1, GPX3, KRT10 for AHT and RBP4, ApoE, KNG1 for YDSK. These biomarkers also biologically linked with the specific TCM syndrome closely. Thus the clinical and biological basis for differentiation and diagnosis of HIV/AIDs TCM syndromes were provided for the first time, providing more opportunities for stable exertion and better application of TCM efficacy and superiority in HIV/AIDS treatment.
Sun, Bing; Bai, Yuxin; Zhang, Liyuan; Gong, Linlin; Qi, Xiaoyu; Li, Huizhen; Wang, Faming; Chi, Xinming; Jiang, Yulin; Shao, Shujuan
Lung cancer remains the leading cancer killer around the world. It's crucial to identify newer mechanism-based targets to effectively manage lung cancer. Annexin A5 (ANXA5) is a protein kinase C inhibitory protein and calcium dependent phospholipid-binding protein, which may act as an endogenous regulator of various pathophysiological processes. However, its molecular mechanism in lung cancer remains poorly understood. This study was designed to determine the mechanism of ANXA5 in lung cancer with a hope to obtain useful information to provide a new therapeutic target. We used a stable isotope dimethyl labeling based quantitative proteomic method to identify differentially expressed proteins in NSCLC cell lines after ANXA5 transfection. Out of 314 proteins, we identified 26 and 44 proteins that were down- and up-regulated upon ANXA5 modulation, respectively. The IPA analysis revealed that glycolysis and gluconeogenesis were the predominant pathways modulated by ANXA5. Multiple central nodes, namely HSPA5, FN1, PDIA6, ENO1, ALDOA, JUP and KRT6A appeared to occupy regulatory nodes in the protein-protein networks upon ANXA5 modulation. Taken together, ANXA5 appears to have pleotropic effects, as it modulates multiple key signaling pathways, supporting the potential usefulness of ANXA5 as a potential target in lung cancer. This study might provide a new insight into the mechanism of ANXA5 in lung cancer.
Full Text Available Lung cancer remains the leading cancer killer around the world. It's crucial to identify newer mechanism-based targets to effectively manage lung cancer. Annexin A5 (ANXA5 is a protein kinase C inhibitory protein and calcium dependent phospholipid-binding protein, which may act as an endogenous regulator of various pathophysiological processes. However, its molecular mechanism in lung cancer remains poorly understood. This study was designed to determine the mechanism of ANXA5 in lung cancer with a hope to obtain useful information to provide a new therapeutic target. We used a stable isotope dimethyl labeling based quantitative proteomic method to identify differentially expressed proteins in NSCLC cell lines after ANXA5 transfection. Out of 314 proteins, we identified 26 and 44 proteins that were down- and up-regulated upon ANXA5 modulation, respectively. The IPA analysis revealed that glycolysis and gluconeogenesis were the predominant pathways modulated by ANXA5. Multiple central nodes, namely HSPA5, FN1, PDIA6, ENO1, ALDOA, JUP and KRT6A appeared to occupy regulatory nodes in the protein-protein networks upon ANXA5 modulation. Taken together, ANXA5 appears to have pleotropic effects, as it modulates multiple key signaling pathways, supporting the potential usefulness of ANXA5 as a potential target in lung cancer. This study might provide a new insight into the mechanism of ANXA5 in lung cancer.
Full Text Available The skin is a highly regenerative organ which plays critical roles in protecting the body and sensing its environment. Consequently, morbidity and mortality associated with skin defects represent a significant health issue. To identify genes important in skin development and homeostasis, we have applied a high throughput, multi-parameter phenotype screen to the conditional targeted mutant mice generated by the Wellcome Trust Sanger Institute's Mouse Genetics Project (Sanger-MGP. A total of 562 different mouse lines were subjected to a variety of tests assessing cutaneous expression, macroscopic clinical disease, histological change, hair follicle cycling, and aberrant marker expression. Cutaneous lesions were associated with mutations in 23 different genes. Many of these were not previously associated with skin disease in the organ (Mysm1, Vangl1, Trpc4ap, Nom1, Sparc, Farp2, and Prkab1, while others were ascribed new cutaneous functions on the basis of the screening approach (Krt76, Lrig1, Myo5a, Nsun2, and Nf1. The integration of these skin specific screening protocols into the Sanger-MGP primary phenotyping pipelines marks the largest reported reverse genetic screen undertaken in any organ and defines approaches to maximise the productivity of future projects of this nature, while flagging genes for further characterisation.
Full Text Available Intervertebral disc (IVD cell therapy with unconditioned 2D expanded mesenchymal stem cells (MSC is a promising concept yet challenging to realize. Differentiation of MSCs by nonviral gene delivery of growth and differentiation factor 5 (GDF5 by electroporation mediated gene transfer could be an excellent source for cell transplantation. Human MSCs were harvested from bone marrow aspirate and GDF5 gene transfer was achieved by in vitro electroporation. Transfected cells were cultured as monolayers and as 3D cultures in 1.2% alginate bead culture. MSC expressed GDF5 efficiently for up to 21 days. The combination of GDF5 gene transfer and 3D culture in alginate showed an upregulation of aggrecan and SOX9, two markers for chondrogenesis, and KRT19 as a marker for discogenesis compared to untransfected cells. The cells encapsulated in alginate produced more proteoglycans expressed in GAG/DNA ratio. Furthermore, GDF5 transfected MCS injected into an IVD papain degeneration organ culture model showed a partial recovery of the GAG/DNA ratio after 7 days. In this study we demonstrate the potential of GDF5 transfected MSC as a promising approach for clinical translation for disc regeneration.
Full Text Available Pachyonychia congenita (PC comprises a group of rare autosomal dominant genetic disorders that involve ectodermal dysplasia. It is characterized by hypertrophic nail dystrophy, focal palmoplantar keratoderma, follicular keratoses, and oral leukokeratosis. Historically, PC has been subdivided into two subtypes, PC-1 or PC-2, on the basis of clinical presentation. However, differential diagnosis based on clinical grounds, especially in young and/or not fully penetrant patients, can be difficult. In addition, clinical analysis of the large case series has shown that there is considerable phenotypic overlap between these two subtypes recently. Based on the advent of molecular genetics and the identification of the genes causing PC, more specific nomenclature has been adopted. Therefore, diagnosis at the molecular level is useful and important to confirm the clinical impression. In this report, we describe two typical cases of PC with mutation analysis revealed a small deletion (514_516delACC, Asn172del and a point mutation (487 G > A, GAG → AAG, Glu163Lys in the KRT6A gene.
Xing Chungen; Yang Xiaodong; Zhou Liying; Wu Yongyou; Jiang Yinfen; Dai Hong; Lv Xiaodong; Gong Wei
The screening of radiosensitive genes of human colorectal cancer was made by gene chip. Two human colorectal cancer cell lines LOVO and SW480 were cultivated and the total RNA was extracted from at least lxl0 7 cells. Then the gene expression profiling was performed by HG-U133 Plus 2.0 Array and the difference of gene expression has been analyzed. The results shows that there are 16882 genes expressed in LOVO cell and 17114 genes expressed in SW480 cell through gene expression profiling. It has been found that the genes with 2-fold expressed differentially include 908 genes up-regulated and 1312 genes down-regulated. The same genes, such as Fas and NFkB which is up-regulated, Caspas6, and RAD21 which is down-regulated, have been proved to be related to radiosensitivity. The genes with high expression level including CEACAM5, THBS1, SERPINE2, ARL7, HPGD in LOVO cell may also be related to the radiosensitivity. And the genes with high expression level including SCD, NQ01, LYZ, KRT20, ATP1B1 in SW480 cell may be related to the radioresistance of human colorectal cancer. It could be concluded that the radiosensitivity of colorectal cancer can be reflected from gene and protein expression level. And gene expression profiling is a fast and sensitive tool to predict the radiosensitivity and screen radiosensitive genes of colorectal cancer. (authors)
Full Text Available Mice and human patients with impaired vitamin D receptor (VDR signaling have normal developmental hair growth but display aberrant post-morphogenic hair cycle progression associated with alopecia. In addition, VDR–/– mice exhibit impaired cutaneous wound healing. We undertook experiments to determine whether the stress-inducible regulator of energy homeostasis, DNA damage-inducible transcript 4 (Ddit4, is involved in these processes. By analyzing hair cycle activation in vivo, we show that VDR−/− mice at day 14 exhibit increased Ddit4 expression within follicular stress compartments. At day 29, degenerating VDR−/− follicular keratinocytes, but not bulge stem cells, continue to exhibit an increase in Ddit4 expression. At day 47, when normal follicles and epidermis are quiescent and enriched for Ddit4, VDR−/− skin lacks Ddit4 expression. In a skin wound healing assay, the re-epithelialized epidermis in wildtype (WT but not VDR−/− animals harbor a population of Ddit4- and Krt10-positive cells. Our study suggests that VDR regulates Ddit4 expression during epidermal homeostasis and the wound healing process, while elevated Ddit4 represents an early growth-arresting stress response within VDR−/− follicles.
Yang, Ruifeng; Zheng, Ying; Burrows, Michelle; Liu, Shujing; Wei, Zhi; Nace, Arben; Guo, Wei; Kumar, Suresh; Cotsarelis, George; Xu, Xiaowei
Epithelial stem cells (EpSCs) in the hair follicle bulge are required for hair follicle growth and cycling. The isolation and propagation of human EpSCs for tissue engineering purposes remains a challenge. Here we develop a strategy to differentiate human iPSCs (hiPSCs) into CD200+/ITGA6+ EpSCs that can reconstitute the epithelial components of the hair follicle and interfollicular epidermis. The hiPSC-derived CD200+/ITGA6+ cells show a similar gene expression signature as EpSCs directly isolated from human hair follicles. Human iPSC-derived CD200+/ITGA6+ cells are capable of generating all hair follicle lineages including the hair shaft, and the inner and outer root sheaths in skin reconstitution assays. The regenerated hair follicles possess a KRT15+ stem cell population and produce hair shafts expressing hair-specific keratins. These results suggest an approach for generating large numbers of human EpSCs for tissue engineering and new treatments for hair loss, wound healing and other degenerative skin disorders.
Islam M. Saadeldin
Full Text Available Trophectoderm cells are the foremost embryonic cells to differentiate with prospective stem-cell properties. In the current study, we aimed at improving the current approach for trophoblast culture by using granulosa cells as feeders. Porcine granulosa cells (PGCs compared to the conventional mouse embryonic fibroblasts (MEFs were used to grow trophectoderm cells from hatched bovine blastocysts. Isolated trophectoderm cells were monitored and displayed characteristic epithelial/cuboidal morphology. The isolated trophectoderm cells expressed mRNA of homeobox protein (CDX2, cytokeratin-8 (KRT8, and interferon tau (IFNT. The expression level was higher on PGCs compared to MEFs throughout the study. In addition, primary trophectoderm cell colonies grew faster on PGCs, with a doubling time of approximately 48 hrs, compared to MEFs. PGCs feeders produced a fair amount of 17β-estradiol and progesterone. We speculated that the supplementation of sex steroids and still-unknown factors during the trophoblasts coculture on PGCs have helped to have better trophectoderm cell’s growth than on MEFs. This is the first time to use PGCs as feeders to culture trophectoderm cells and it proved superior to MEFs. We propose PGCs as alternative feeders for long-term culture of bovine trophectoderm cells. This model will potentially benefit studies on the early trophoblast and embryonic development in bovines.
Zhao, Hengguang; Rieger, Sandra; Abe, Koichiro; Hewison, Martin; Lisse, Thomas S
Mice and human patients with impaired vitamin D receptor (VDR) signaling have normal developmental hair growth but display aberrant post-morphogenic hair cycle progression associated with alopecia. In addition, VDR -/- mice exhibit impaired cutaneous wound healing. We undertook experiments to determine whether the stress-inducible regulator of energy homeostasis, DNA damage-inducible transcript 4 (Ddit4), is involved in these processes. By analyzing hair cycle activation in vivo, we show that VDR -/- mice at day 14 exhibit increased Ddit4 expression within follicular stress compartments. At day 29, degenerating VDR -/- follicular keratinocytes, but not bulge stem cells, continue to exhibit an increase in Ddit4 expression. At day 47, when normal follicles and epidermis are quiescent and enriched for Ddit4, VDR -/- skin lacks Ddit4 expression. In a skin wound healing assay, the re-epithelialized epidermis in wildtype (WT) but not VDR -/- animals harbor a population of Ddit4- and Krt10-positive cells. Our study suggests that VDR regulates Ddit4 expression during epidermal homeostasis and the wound healing process, while elevated Ddit4 represents an early growth-arresting stress response within VDR -/- follicles.
Munne, Pauliina M.; Gu, Yuexi; Tumiati, Manuela; Gao, Ping; Koopal, Sonja; Uusivirta, Sanna; Sawicki, Janet; Wei, Gong-Hong; Kuznetsov, Sergey G.
Multiple observations suggest a cell type-specific role for TP53 in mammary epithelia. We developed an in vitro assay, in which primary mouse mammary epithelial cells (mMECs) progressed from lumenal to basal-like phenotypes based on expression of Krt18 or ΔNp63, respectively. Such transition was markedly delayed in Trp53-/- mMECs suggesting that Trp53 is required for specification of the basal, but not lumenal cells. Evidence from human basal-like cell lines suggests that TP53 may support the activity of ΔNp63 by preventing its translocation from nucleoplasm into nucleoli. In human lumenal cells, activation of TP53 by inhibiting MDM2 or BRCA1 restored the nucleoplasmic expression of ΔNp63. Trp53-/- mMECs eventually lost epithelial features resulting in upregulation of MDM2 and translocation of ΔNp63 into nucleoli. We propose that TP63 may contribute to TP53-mediated oncogenic transformation of epithelial cells and shed light on tissue- and cell type-specific biases observed for TP53-related cancers.
Full Text Available Aminoacyl-tRNA synthetases (ARSs and ARS-interacting multifunctional proteins (AIMPs exhibit remarkable functional versatility beyond their catalytic activities in protein synthesis. Their non-canonical functions have been pathologically linked to cancers. Here we described our integrative genome-wide analysis of ARSs to show cancer-associated activities in glioblastoma multiforme (GBM, the most aggressive malignant primary brain tumor. We first selected 23 ARS/AIMPs (together referred to as ARSN, 124 cancer-associated druggable target genes (DTGs and 404 protein-protein interactors (PPIs of ARSs using NCI's cancer gene index. 254 GBM affymetrix microarray data in The Cancer Genome Atlas (TCGA were used to identify the probe sets whose expression were most strongly correlated with survival (Kaplan-Meier plots versus survival times, log-rank t-test <0.05. The analysis identified 122 probe sets as survival signatures, including 5 of ARSN (VARS, QARS, CARS, NARS, FARS, and 115 of DTGs and PPIs (PARD3, RXRB, ATP5C1, HSP90AA1, CD44, THRA, TRAF2, KRT10, MED12, etc. Of note, 61 survival-related probes were differentially expressed in three different prognosis subgroups in GBM patients and showed correlation with established prognosis markers such as age and phenotypic molecular signatures. CARS and FARS also showed significantly higher association with different molecular networks in GBM patients. Taken together, our findings demonstrate evidence for an ARSN biology-dominant contribution in the biology of GBM.
Full Text Available Microgravity induces three-dimensional (3D growth in numerous cell types. Despite substantial efforts to clarify the underlying mechanisms for spheroid formation, the precise molecular pathways are still not known. The principal aim of this paper is to compare static 1g-control cells with spheroid forming (MCS and spheroid non-forming (AD thyroid cancer cells cultured in the same flask under simulated microgravity conditions. We investigated the morphology and gene expression patterns in human follicular thyroid cancer cells (UCLA RO82-W-1 cell line after a 24 h-exposure on the Random Positioning Machine (RPM and focused on 3D growth signaling processes. After 24 h, spheroid formation was observed in RPM-cultures together with alterations in the F-actin cytoskeleton. qPCR indicated more changes in gene expression in MCS than in AD cells. Of the 24 genes analyzed VEGFA, VEGFD, MSN, and MMP3 were upregulated in MCS compared to 1g-controls, whereas ACTB, ACTA2, KRT8, TUBB, EZR, RDX, PRKCA, CAV1, MMP9, PAI1, CTGF, MCP1 were downregulated. A pathway analysis revealed that the upregulated genes code for proteins, which promote 3D growth (angiogenesis and prevent excessive accumulation of extracellular proteins, while genes coding for structural proteins are downregulated. Pathways regulating the strength/rigidity of cytoskeletal proteins, the amount of extracellular proteins, and 3D growth may be involved in MCS formation.
Pearce, John A.
Apoptosis is an especially important process affecting disease states from HIV-AIDS to auto-immune disease to cancer. A cascade of initiator and executioner capsase functional proteins is the hallmark of apoptosis. When activated the various caspases activate other caspases or cleave structural proteins of the cytoskeleton, resulting in "blebbing" of the plasma membrane forming apoptotic bodies that completely enclose the disassembled cellular components. Containment of the cytosolic components within the apoptotic bodies differentiates apoptosis from necroptosis and necrosis, both of which release fragmented cytosol and other cellular constituents into the intracellular space. Biochemical models of caspase activation reveal the extensive feedback loops characteristic of apoptosis. They clearly explain the failure of Arrhenius models to give accurate predictions of cell survival curves in hyperthermic heating protocols. Nevertheless, each of the individual reaction velocities can reasonably be assumed to follow Arrhenius kinetics. If so, the thermal sensitivity of the reaction velocity to temperature elevation is: ∂k/∂T = Ea [k/RT2]. Particular reaction steps described by higher activation energies, Ea, are likely more thermally-sensitive than lower energy reactions and may initiate apoptosis in the absence of other stress signals. Additionally, while the classical irreversible Arrhenius formulation fails to accurately represent many cell survival and/or dye uptake curves - those that display an early stage shoulder region - an expanded reversible model of the law of mass action equation seems to prove effective and is directly based on a firm theoretical thermodynamic foundation.
Sedcole J Richard
Full Text Available Abstract Background Feral sheep are considered to be a source of genetic variation that has been lost from their domestic counterparts through selection. Methods This study investigates variation in the genes KRTAP1-1, KRT33, ADRB3 and DQA2 in Merino-like feral sheep populations from New Zealand and its offshore islands. These genes have previously been shown to influence wool, lamb survival and animal health. Results All the genes were polymorphic, but no new allele was identified in the feral populations. In some of these populations, allele frequencies differed from those observed in commercial Merino sheep and other breeds found in New Zealand. Heterozygosity levels were comparable to those observed in other studies on feral sheep. Our results suggest that some of the feral populations may have been either inbred or outbred over the duration of their apparent isolation. Conclusion The variation described here allows us to draw some conclusions about the likely genetic origin of the populations and selective pressures that may have acted upon them, but they do not appear to be a source of new genetic material, at least for these four genes.
Kim, Kang-Hoon; Chung, Won-Seok; Kim, Yoomi; Kim, Ki-Suk; Lee, In-Seung; Park, Ji Young; Jeong, Hyeon-Soo; Na, Yun-Cheol; Lee, Chang-Hun; Jang, Hyeung-Jin
Facilitation of the wound healing process is important because a prolonged wound site increases pain and the risk of infection. In oriental medicine, an extract of Morus alba root (MA) has usually been prescribed as traditional treatment for accelerating wound healing, and it has been proven to be safe for centuries. To study the molecular mechanism of MA-mediated skin wound healing, we performed a primary cell culture and a skin explant culture and observed significant difference between the groups with and without MA extract. In the cellular system, a real-time cell analysis and real-time quantitative PCR were performed. It was found that MA extract enhanced proliferation in a dose-dependent manner on Kera-308 cell line, and up-regulated keratin expression including wound-induced Krt6a. In skin explant culture, the mRNA level derived from cell outgrowth displayed a tendency toward more up-regulated mRNA associated keratin filaments and toward a more up-regulated mRNA level of C-X-C motif chemokine 12 (CXCL12) and a chemokine receptor 4 (CXCR4) axis signaling pathway downstream. In this process, we concluded that MA extract had a scientific possibility of wound repair by increasing intracellular and extracellular supports and by inducing a CXCL12/CXCR4 signaling pathway. Copyright © 2015 John Wiley & Sons, Ltd.
Adami, Guy R; O'Callaghan, Thomas N; Kolokythas, Antonia; Cabay, Robert J; Zhou, Yalu; Schwartz, Joel L
The genes for PFN1 and TMSB4 are both highly expressed in oral tissue and both encode actin monomer binding proteins thought to play a role in cell motility and possibly other crucial parts of tumor progression. Oral brush cytology of epithelium from oral squamous cell carcinoma (OSCC) was used to measure PFN1 and TMSB4 mRNA in OSCC, while immunohistochemical analysis of tissue was used to check protein levels. High but variable expression of mRNAs encoding these two proteins was observed suggesting they may contribute to tumor characteristics in a subset of OSCCs. Both proteins were highly expressed in normal appearing basal epithelium, in the cytoplasm, and perinuclear area, while expression was minimal in upper epithelial layers. In OSCCs, expression of these proteins varied. In tumors classified as later stage, based on size and/or lymph node involvement, PFN1 levels were lower in tumor epithelium. A control gene, KRT13, showed expression in normal differentiated basal and suprabasal oral mucosa epithelial cells and as reported was lost in OSCC cells. Loss of PFN1 in tumor cells has been associated with lymph node invasion and metastasis in other tumor types, strengthening the argument that the protein has the potential to be a tumor suppressor in late-stage OSCC. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Zhang, Bin; Meng, Bo; Viloria, Edward; Naveau, Adrien; Ganss, Bernhard; Jheon, Andrew H
The aim of this study was to evaluate the role of epithelial signal transducer and activator of transcription 3 (STAT3) in mouse incisor amelogenesis. Since Stat3 is expressed in the epithelial component of developing and adult mouse teeth, we generated and analyzed Krt14Cre/+;Stat3fl/fl mutant mice in which Stat3 was inactivated in epithelia including ameloblast progenitors and ameloblasts, the cells responsible for enamel formation. Histological analysis showed little enamel matrix in mutant incisors compared to controls. Delayed incisor enamel mineralization was demonstrated using micro-computed X-ray tomography analysis and was supported by an increase in the pre-expression distance of enamel-enriched proteins such as amelogenin, ameloblastin, and kallikrein-4. Lastly, scanning electron microscopy analysis showed little enamel mineralization in mutant incisors underneath the mesial root of the 1st molar; however, the micro-architecture of enamel mineralization was similar in the erupted portion of control and mutant incisors. Taken together, our findings demonstrate for the first time that the absence of epithelial Stat3 in mice leads to delayed incisor amelogenesis. © 2018 S. Karger AG, Basel.
Full Text Available The detection of breast carcinoma cells in effusions is associated with rapidly fatal outcome, but these cells are poorly characterized at the molecular level. This study compared the gene array signatures of breast carcinoma cells in primary carcinomas and effusions. The genetic signature of 10 primary tumors and 10 effusions was analyzed using the Array-Ready Oligo set for the Human Genome platform. Results for selected genes were validated using PCR, Western blotting, and immunohistochemistry. Array analysis identified 255 significantly downregulated and 96 upregulated genes in the effusion samples. The majority of differentially expressed genes were part of pathways involved in focal adhesion, extracellular matrix-cell interaction, and the regulation of the actin cytoskeleton. Genes that were upregulated in effusions included KRT8, BCAR1, CLDN4, VIL2, while DCN, CLDN19, ITGA7, and ITGA5 were downregulated at this anatomic site. PCR, Western blotting, and immunohistochemistry confirmed the array findings for BCAR1, CLDN4, VIL2, and DCN. Our data show that breast carcinoma cells in primary carcinomas and effusions have different gene expression signatures, and differentially express a large number of molecules related to adhesion, motility, and metastasis. These differences may have a critical role in designing therapy and in prognostication for patients with metastatic disease localized to the serosal cavities.
Full Text Available - L. Sluimers, M.E. Osborne, Strategic hamlets in South Viet-nam. A survey and a comparison. Southeast Asia Program, Department of Asian Studies, Data Paper no. 55. Ithaca, Cornell University Press, 1965. XII, 66 blz., X, krt. - L. Sluimers, F.B. Weinstein, Vietnam’s unheld elections: The failure to carry out the 1956 reunification elections and the effect on Hanoi’s present outlook. Data Paper: No. 60, Southeast Asia Program. Department of Asian Studies. Cornell University. Ithaca, Cornell University Press, 1966. VII, 65 blz., XIII. - L. Sluimers, D.E. Weatherbee, Ideology in Indonesia: Sukarno’s Indonesian revolution. Monograph Series No. 8. Southeast Asia Studies, Yale University, 1966. X, 135 blz., VII. - J.H.A. Logemann, Donald E. Weatherbee, Ideology in Indonesia: Soekarno’s Indonesian Revolution. Southeast Asia Studies Monograph Series no. 8. Yale University, 1967. 135 pp., Charts, glossary. - H.J. de Graaf, A.B. Ward, Rajah’s servant. With a preface by Robert M. Pringle and Otto C. Doering III. Data Paper: No. 61. South East Asia Program. Department of Asian Studies. Cornell University, Ithaca, New York. Nov. 1966. - J.C. Anceaux, Viktor Krupa, Morpheme and word in Maori. (Janua Linguarum, Series Practica. XLVI. Mouton & Co., The Hague 1966. 83 pp. - G.D. van Wengen, Surinam. Grammofoonplaat, uitgave Philips. Serie: “Song and sound the World Around”. Stereo 831 231 PY (ook als mono speelbaar, 33 1/3 t.
Predicting acute side effects of stimulant medication in pediatric attention deficit/hyperactivity disorder: data from quantitative electroencephalography, event-related potentials, and a continuous-performance test
Full Text Available Geir Ogrim,1–3 Knut A Hestad,3,4 Jan Ferenc Brunner,3,5,6 Juri Kropotov3,7,8 1Neuropsychiatric Unit, Østfold Hospital Trust, Fredrikstad, Norway; 2National Resource Center for ADHD, Tourettes' Syndrome and Narcolepsy, Oslo, Norway; 3Institute of Psychology, Norwegian University of Science and Technology (NTNU, Trondheim, Norway; 4Division of Mental Health, Innlandet Hospital Trust, Brumunddal, Norway; 5Department of Physical Medicine and Rehabilitation, St Olav's Hospital, Trondheim, Norway; 6Department of Neuroscience, NTNU, Trondheim, Norway; 7Institute of the Human Brain, Russian Academy of Sciences, Saint Petersburg, Russia; 8Department of Neuropsychology, Andrzej Frycz Modrzewski Krakow University, Krakow, Poland Background: The aim of this study was to search for predictors of acute side effects of stimulant medication in pediatric attention deficit/hyperactivity disorder (ADHD, emphasizing variables from quantitative electroencephalography (QEEG, event-related potentials (ERPs, and behavior data from a visual continuous-performance test (VCPT. Methods: Seventy medication-naïve ADHD patients aged 7–16 years were tested with QEEG, including a go/no-go task condition (VCPT from which behavior data and ERPs were extracted, followed by a systematic trial on stimulant medication lasting at least 4 weeks. Based on data from rating scales and interviews, two psychologists who were blind to the QEEG/ERP test results independently rated the patients as having no or small side effects (n = 37 or troublesome side effects (n = 33. We determined if the side effects were related to sex, age, IQ, ADHD subtype, comorbidities, clinical outcome, and variables in QEEG, ERPs, and VCPT. Results: There was a moderate negative correlation between clinical outcome and side effects. Three variables were significantly associated with side effects in a multivariate logistic regression analysis. In the ERP independent component – contingent negative variation
Full Text Available Aleksandra Kotlinska-Lemieszek,1 Pål Klepstad,2,3,6 Dagny Faksvåg Haugen2,4,5 1Palliative Medicine Chair and Department, University Hospital of the Lord’s Transfiguration, Karol Marcinkowski University of Medical Sciences, Poznan, Poland; 2European Palliative Care Research Centre, Faculty of Medicine, Norwegian University of Science and Technology,Trondheim, Norway; 3Department of Anaesthesiology and Intensive Care Medicine, St Olavs Hospital, Trondheim, Norway; 4Regional Centre of Excellence for Palliative Care, Haukeland University Hospital, Bergen, Norway; 5Department of Clinical Medicine K1, University of Bergen, Bergen, Norway; 6Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway Background: Opioids are the most frequently used drugs to treat pain in cancer patients. In some patients, however, opioids can cause adverse effects and drug–drug interactions. No advice concerning the combination of opioids and other drugs is given in the current European guidelines. Objective: To identify studies that report clinically significant drug–drug interactions involving opioids used for pain treatment in adult cancer patients. Design and data sources: Systematic review with searches in Embase, MEDLINE, and Cochrane Central Register of Controlled Trials from the start of the databases (Embase from 1980 through January 2014. In addition, reference lists of relevant full-text papers were hand-searched. Results: Of 901 retrieved papers, 112 were considered as potentially eligible. After full-text reading, 17 were included in the final analysis, together with 15 papers identified through hand-searching of reference lists. All of the 32 included publications were case reports or case series. Clinical manifestations of drug–drug interactions involving opioids were grouped as follows: 1 sedation and respiratory depression, 2 other central nervous system symptoms, 3 impairment of pain
Full Text Available Danai Tavonga Zhou,1,2 Olav Oektedalen,3 Sandra Shawarira-Bote,4 Babill Stray-Pedersen5 1Department of Medical Laboratory Sciences, College of Health Sciences, University of Zimbabwe, Avondale, Harare, Zimbabwe; 2Institute of Clinical Medicine, University of Oslo, 3Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway; 4Newlands Clinic, Harare, Zimbabwe; 5Institute of Clinical Medicine, University in Oslo and Womens Clinic, Oslo University Hospital, Oslo, Norway Abstract: Dyslipidemia, hypertension, inflammation, and coronary heart disease (CHD are adverse events in human immunodeficiency virus (HIV-infected patients even if they are receiving antiretroviral therapy (ART. Yet, data on CHD risk induced by HIV or ART in sub-Saharan Africa are limited. The aim of this longitudinal study was to describe changes in CHD risk profiles measured by lipids, inflammatory markers, and Framingham scores among HIV-positive patients previously reported from Harare, Zimbabwe. Patients were grouped into ART-experienced patients (n=147 and ART-naïve patients (n=23 and followed up for 9 months. Generalized least squares random-effects modeling was applied to explain changes in total cholesterol (TC, high-density lipoprotein (HDL, low-density lipoprotein, TC/HDL ratio, myeloperoxidase, highly sensitive C-reactive protein, and Framingham scores over the 9-month period. Independent variables included age, sex, monthly earning, body mass index, systolic blood pressure (SBP, diastolic blood pressure, duration of HIV diagnosis, duration of ART, viral load, and CD4 count. In ART-experienced patients, there was a substantial decrease in TC over time, ART-negative patients showed a significant increase in TC and HDL over time, and the increase in TC was associated with high viral load and low duration of HIV diagnosis, while increase in HDL was associated with young age, low body mass index, and low SBP. Framingham risk scores increased with time in
Full Text Available Blanca Tobar-Grande,1 Ricardo Godoy,1 Paulina Bustos,2 Carlos von Plessing,1 Elias Fattal,3,4 Nicolas Tsapis,3,4 Claudia Olave,1 Carolina Gómez-Gaete11Departamento de Farmacia, Facultad de Farmacia, Universidad de Concepción, Concepción, Chile; 2Departamento de Bioquímica Clínica e Inmunología, Facultad de Farmacia, Universidad de Concepción, Concepción, Chile; 3Univ Paris-Sud, Institut Galien Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry, France; 4CNRS, UMR 8612, Faculté de Pharmacie, Châtenay-Malabry, FranceAbstract: In this work, microparticles were prepared by spray-drying using albumin, chondroitin sulfate, and hyaluronic acid as excipients to create a controlled-release methylprednisolone system for use in inflammatory disorders such as arthritis. Scanning electron microscopy demonstrated that these microparticles were almost spherical, with development of surface wrinkling as the methylprednisolone load in the formulation was increased. The methylprednisolone load also had a direct influence on the mean diameter and zeta potential of the microparticles. Interactions between formulation excipients and the active drug were evaluated by x-ray diffraction, differential scanning calorimetry, and thermal gravimetric analysis, showing limited amounts of methylprednisolone in a crystalline state in the loaded microparticles. The encapsulation efficiency of methylprednisolone was approximately 89% in all formulations. The rate of methylprednisolone release from the microparticles depended on the initial drug load in the formulation. In vitro cytotoxic evaluation using THP-1 cells showed that none of the formulations prepared triggered an inflammatory response on release of interleukin-1ß, nor did they affect cellular viability, except for the 9.1% methylprednisolone formulation, which was the maximum test concentration used. The microparticles developed in this study have characteristics amenable to a therapeutic role in
Full Text Available Maria Rasmussen,1 Morten Smærup Olsen,2 Lone Sunde,1,3 Lars Pedersen,2 Olav Bjørn Petersen4 1Department of Clinical Genetics, Aarhus University Hospital, Skejby, 2Department of Clinical Epidemiology, Aarhus University Hospital, Skejby, 3Department of Biomedicine, Aarhus University, Aarhus, 4Department of Gynecology and Obstetrics, Aarhus University Hospital, Skejby, Denmark Objective: Restricting studies of severe congenital malformations to live-born children may introduce substantial bias. In this study, we estimated the attendance to the second-trimester fetal malformation screening program. We also estimated the positive predictive value (PPV of prenatally assigned International Classification of Disease-10 diagnoses recorded in the Danish National Patient Registry (DNPR and the completeness of case registration. We used kidney anomalies as an example. Methods: We identified the proportion of all Danish live-born children from January 1, 2007 to December 31, 2012, who were scanned during the second trimester using the DNPR and the Civil Registration System. Details of all fetuses with specific kidney anomaly diagnoses according to the DNPR were retrieved. The PPV was estimated using the nationwide Astraia database of pregnancy medical charts or traditional medical charts, as gold standard. The completeness was assessed using the total number of cases estimated by the capture–recapture method. Results: Of 372,263 live born infants, 97.3% were scanned during the second trimester. We identified 172 fetuses in the DNPR. Of these, 149 had kidney anomalies according to Astraia or medical chart review, corresponding to a PPV of 87% (95% CI: 81%–91%. The estimated completeness was 43% (95% CI: 38%–49% for the DNPR and 75% (95% CI: 70%–79% for Astraia. Conclusion: Almost all live-born children were scanned during the second trimester in Denmark. However, low completeness may hamper the use of the DNPR for studies of prenatally detected
Full Text Available Camilla Buch Gudde,1,2 Turid Møller Olsø,4 Richard Whittington,1,5,6 Solfrid Vatne,3 1Forensic Department Brøset, Centre for Research and Education in Forensic Psychiatry, St Olavs Hospital, 2Department of Social Work and Health Science, Faculty of Social Science and Technology Management, NTNU, Trondheim, 3Institute of Health and Social Sciences, Molde University College, Molde, 4Norwegian Resource Centre for Community Mental Health, NTNU Social Research AS, 5Department of Neuroscience, Norwegian University of Science and Technology, NTNU, Trondheim, Norway; 6Institute of Psychology, Health and Society, University of Liverpool, Liverpool, UK Background: Aggressive situations occurring within mental health services can harm service users, staff, and the therapeutic environment. There is a consensus that the aggression phenomenon is multidimensional, but the picture is still unclear concerning the complex interplay of causal variables and their respective impact. To date, only a small number of empirical studies include users’ views of relevant factors. The main objective of this review is to identify and synthesize evidence relating to service users’ experiences and views of aggressive situations in mental health settings. Methods: We included qualitative studies of any design reporting on service users’ own experiences of conditions contributing to aggressive situations in mental health care and their views on preventative strategies. Eligible articles were identified through an electronic database search (PsycINFO, PubMed, Ovid Nursing Database, Embase, and CINAHL, hand search, and cross-referencing. Extracted data were combined and interpreted using aspects of thematic synthesis. Results: We reviewed 5,566 records and included 13 studies (ten qualitative and three mixed methods. Service users recognized that both their own mental state and negative aspects of the treatment environment affected the development of aggressive situations
Full Text Available Carlos Cruz-Montecinos,1–3 Diego Godoy-Olave,4 Felipe A Contreras-Briceño,5 Paulina Gutiérrez,4 Rodrigo Torres-Castro,2 Leandro Miret-Venegas,3 Roger M Engel6 1Laboratory of Biomechanics and Kinesiology, San José Hospital, Santiago, Chile; 2Department of Physical Therapy, Faculty of Medicine, University of Chile, Santiago, Chile; 3Unit of Kinesiology and Physical Therapy, San José Hospital, Santiago, Chile; 4Departamento de Kinesiología, Universidad Metropolitana de Ciencias de la Educación, Santiago, Chile; 5Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile; 6Department of Chiropractic, Macquarie University, Sydney, Australia Background and objective: In chronic obstructive pulmonary disease (COPD, accessory respiratory muscles are recruited as a compensatory adaptation to changes in respiratory mechanics. This results in shortening and overactivation of these and other muscles. Manual therapy is increasingly being investigated as a way to alleviate these changes. The aim of this study was to measure the immediate effect on lung function of a soft tissue manual therapy protocol (STMTP designed to address changes in the accessory respiratory muscles and their associated structures in patients with severe COPD.Methods: Twelve medically stable patients (n=12 with an existing diagnosis of severe COPD (ten: GOLD Stage III and two: GOLD Stage IV were included. Residual volume, inspiratory capacity and oxygen saturation (SpO2 were recorded immediately before and after administration of the STMTP. A Student’s t-test was used to determine the effect of the manual therapy intervention (P<0.05.Results: The mean age of the patients was 62.4 years (range 46–77. Nine were male. Residual volume decreased from 4.5 to 3.9 L (P=0.002, inspiratory capacity increased from 2.0 to 2.1 L (P=0.039 and SpO2 increased from 93% to 96% (P=0.001.Conclusion: A single application of an STMTP appears to have the potential to produce
Full Text Available Danai Tavonga Zhou,1,2 Vitaris Kodogo,1 Kudzai Fortunate Vongai Chokuona,1 Exnevia Gomo,1 Olav Oektedalen,3 Babill Stray-Pedersen21Department of Medical Laboratory Sciences, College of Health Sciences, University of Zimbabwe, Avondale, Zimbabwe; 2Institute of Clinical Medicine, University in Oslo, Oslo University Hospital, Oslo, Norway; 3Department of Infectious Diseases, Oslo University Hospital, Oslo, NorwayAbstract: The chronic inflammation induced by human immunodeficiency virus (HIV contributes to increased risk of coronary heart disease (CHD in HIV-infected individuals. HIV-infected patients generally benefit from being treated with antiretroviral drugs, but some antiretroviral agents have side effects, such as dyslipidemia and hyperglycemia. There is general consensus that antiretroviral drugs induce a long-term risk of CHD, although the levels of that risk are somewhat controversial. The intention of this cross-sectional study was to describe the lipid profile and the long-term risk of CHD among HIV-positive outpatients at an HIV treatment clinic in Harare, Zimbabwe. Two hundred and fifteen patients were investigated (females n=165, mean age 39.8 years; males n=50; mean age 42.0 years. Thirty of the individuals were antiretroviral-naïve and 185 had been on antiretroviral therapy (ART for a mean 3.9±3.4 years. All participants had average lipid and glucose values within normal ranges, but there was a small difference between the ART and ART- for total cholesterol (TC and high-density lipoprotein (HDL.Those on a combination of D4T or ZDV/NVP/3TC and PI-based ART were on average oldest and had the highest TC levels. Framingham risk showed 1.4% prevalence of high CHD risk within the next ten years. After univariate analysis age, sex, TC/HDL ratio, HDL, economic earnings and systolic BP were associated with medium to high risk of CHD. After multivariate regression analysis and adjusting for age or sex only age, sex and economic earnings
Aslaksen Aasly, Kari; Meyer, Gurli Birgitte; Kløve Keiding, Jakob; Langås, Rune; Lund, Vegard
The Nidaros Cathedral situated in Trondheim, Norway is a restored cathedral resting on the remnants of an original medieval church sanctified St Olav. The cathedral became one of the most important sanctuary for pilgrimage during the Middle Ages and still is today. In a European context the cathedral, along with a certain group of other churches and monasteries in Norway, is unique by being build from soapstone (steatite). This talc and chlorite dominated metamorphic rock is relatively soft, heat resistant and dense making the material ideal for cooking pots, stoves and all kinds of utensils. Soapstone has therefore been appreciated, used and quarried since the Stone Age in Norway. At the onset of Christianity the choice of soapstone from harder rock types was not difficult for the building owners combining the vision of stone churches in Norway with the skills of wood carving traditions of local handicraftsmen. The best example is the Nidaros Cathedral built in the 11th to 14th century. In 1869, the Nidaros Cathedral Restoration Workshop (NDR) was founded with the purpose of restoring the cathedral using original craftsman's techniques and authentic materials. The restoration was originally completed in 1969, but is still ongoing due to weathering of certain used soapstone types. A major challenge remains to find soapstone resources of the right quality. Core issues relate to avoid rocks with cracks and cleavage, a demand for homogeneity, maintaining esthetic authenticity, resistance to weathering (disintegration) and last but not least the ultimatum of workability. Thus locating new soapstone resources depends strongly on geological understanding, quarry experience and stone carver's knowledge. The present work is based on close cooperation between stone carvers and geologists in a common goal of uniting knowledge and experience in defining qualities of soapstone for various purposes of restoration. Cooperate observations of geology and carving properties in the
Moore, Emilee; Evnitskaya, Natalia; Ramos-de Robles, S. Lizette
In this paper we reflect on the article, Science education in a bilingual class: problematising a translational practice, by Zeynep Ünsal, Britt Jakobson, Bengt-Olav Molander and Per-Olaf Wickman (Cult Stud Sci Educ, 10.1007/s11422-016-9747-3). In their article, the authors present the results of a classroom research project by responding to one main question: How is continuity between everyday language and the language of science construed in a bilingual science classroom where the teacher and the students do not speak the same minority language? Specifically, Ünsal et al. examine how bilingual students construe relations between everyday language and the language of science in a class taught in Swedish, in which all students also spoke Turkish, whereas the teacher also spoke Bosnian, both being minority languages in the context of Swedish schools. In this forum, we briefly discuss why close attention to bilingual dynamics emerging in classrooms such as those highlighted by Ünsal et al. matters for science education. We continue by discussing changing ontologies in relation to linguistic diversity and education more generally. Recent research in bilingual immersion classroom settings in so-called "content" subjects such as Content and Language Integrated Learning, is then introduced, as we believe this research offers some significant insights in terms of how bilingualism contributes to knowledge building in subjects such as science. Finally, we offer some reflections in relation to the classroom interactional competence needed by teachers in linguistically diverse classrooms. In this way, we aim to further the discussion initiated by Ünsal et al. and to offer possible frameworks for future research on bilingualism in science education. In their article, Ünsal et al. conclude the analysis of the classroom data by arguing in favor of a translanguaging pedagogy, an approach to teaching and learning in which students' whole language repertoires are used as
Prestmo, Anders; Hagen, Gunhild; Sletvold, Olav; Helbostad, Jorunn L; Thingstad, Pernille; Taraldsen, Kristin; Lydersen, Stian; Halsteinli, Vidar; Saltnes, Turi; Lamb, Sarah E; Johnsen, Lars G; Saltvedt, Ingvild
ward improved mobility at 4 months, compared with the usual orthopaedic care. The results suggest that the treatment of older patients with hip fractures should be organised as orthogeriatric care. Norwegian Research Council, Central Norway Regional Health Authority, St Olav Hospital Trust and Fund for Research and Innovation, Liaison Committee between Central Norway Regional Health Authority and the Norwegian University of Science and Technology, the Department of Neuroscience at the Norwegian University of Science and Technology, Foundation for Scientific and Industrial Research at the Norwegian Institute of Technology (SINTEF), and the Municipality of Trondheim. Copyright © 2015 Elsevier Ltd. All rights reserved.
Gaytan, F; Morales, C; Roa, J; Tena-Sempere, M
Is keratin 8/18 (K8/K18) expression linked to cell death/survival events in the human granulosa cell lineage? A close association exists between changes in K8/K18 expression and cell death/survival events along the human granulosa cell lineage lifespan. In addition to their structural and mechanical functions, K8/K18 play essential roles regulating cell death, survival and differentiation in several non-gonadal epithelial tissues. Transfection of the granulosa-like tumor KGN cells with siRNA to interfere KRT8 and KRT18 expression increases FAS-mediated apoptosis, while an inverse association between K8/K18 expression and cell death has been found in the bovine antral follicles and corpus luteum. Yet, only fragmentary and inconclusive information exists regarding K8/K18 expression in the human ovary. Expression of K8/K18 was assessed by immunohistochemistry at different stages of the granulosa cell lineage, from flattened granulosa cells in primordial follicles to fully luteinized granulosa-lutein cells in the corpus luteum (including corpus luteum of pregnancy). Immunohistochemical detection of K8/K18 was conducted in 40 archival ovarian samples from women aged 17-39 years. K8/K18 expression was analyzed at the different stages of follicle development and corpus luteum lifespan. The proportions of primordial follicles showing all K8/K18-positive, all K8/K18 negative, or a mixture of K8/K18 negative and positive granulosa cells were quantified in 18 ovaries, divided into three age groups: ≤ 25 years (N = 6), 26-30 (N = 6) and 31-36 (N = 6) years. A total number of 1793 primordial, 750 transitional and 140 primary follicles were scored. A close association was found between changes in K8/K18 expression and cell death/cell survival events in the human granulosa cell lineage. Large secondary and early antral follicles (most of them undergoing atresia) and regressing corpora lutea displayed low/absent K8/K18 expression. Conversely, early growing and some large antral
Full Text Available Breast cancer prognosis and treatment is highly dependent on the molecular features of the primary tumors. These tumors release specific molecules into the environment that trigger characteristic responses into the circulatory cells. In this study we investigated the expression pattern of 84 genes known to be involved in breast cancer signaling in the peripheral blood of breast cancer patients with ER-, PR- primary tumors. The patients were grouped according to Her2 expression on the primary tumors in Her2+ and Her2- cohorts. Transcriptional analysis revealed 15 genes to be differentially expressed between the two groups highlighting that Her2 signaling in primary tumors could be associated with specific blood gene expression. We found CCNA1 to be up-regulated, while ERBB2, RASSF1, CDH1, MKI67, GATA3, GLI1, SFN, PTGS2, JUN, NOTCH1, CTNNB1, KRT8, SRC, and HIC1 genes were down-regulated in the blood of triple negative breast cancer patients compared to Her2+ cohort. IPA network analysis predicts that the identified genes are interconnected and regulate each other. These genes code for cell cycle regulators, cell adhesion molecules, transcription factors or signal transducers that modulate immune signaling, several genes being also associated with cancer progression and treatment response. These results indicate an altered immune signaling in the peripheral blood of triple negative breast cancer patients. The involvement of the immune system is necessary in favorable treatment response, therefore these results could explain the low response rates observed for triple negative breast cancer patients.
Yang, Qiwei; Mas, Aymara; Diamond, Michael P.; Al-Hendy, Ayman
Uterine leiomyomas, also known as uterine fibroids, are the most common pelvic tumors, occurring in nearly 70% of all reproductive-aged women and are the leading indication for hysterectomy worldwide. The development of uterine leiomyomas involve a complex and heterogeneous constellation of hormones, growth factors, stem cells, genetic, and epigenetic abnormalities. An increasing body of evidence emphasizes the important contribution of epigenetics in the pathogenesis of leiomyomas. Genome-wide methylation analysis demonstrates that a subset of estrogen receptor (ER) response genes exhibit abnormal hypermethylation levels that are inversely correlated with their RNA expression. Several tumor suppressor genes, including Kruppel-like factor 11 (KLF11), deleted in lung and esophageal cancer 1 (DLEC1), keratin 19 (KRT19), and death-associated protein kinase 1 (DAPK1) also display higher hypermethylation levels in leiomyomas when compared to adjacent normal tissues. The important role of active DNA demethylation was recently identified with regard to the ten-eleven translocation protein 1 and ten-eleven translocation protein 3-mediated elevated levels of 5-hydroxymethylcytosine in leiomyoma. In addition, both histone deacetylase and histone methyltransferase are reported to be involved in the biology of leiomyomas. A number of deregulated microRNAs have been identified in leiomyomas, leading to an altered expression of their targets. More recently, the existence of side population (SP) cells with characteristics of tumor-initiating cells have been characterized in leiomyomas. These SP cells exhibit a tumorigenic capacity in immunodeficient mice when exposed to 17β-estradiol and progesterone, giving rise to fibroid-like tissue in vivo. These new findings will likely enhance our understanding of the crucial role epigenetics plays in the pathogenesis of uterine leiomyomas as well as point the way to novel therapeutic options. PMID:25922306
Full Text Available - G.N. Appell, Michael B. Leigh, Checklist of holdings on Borneo in the Cornell University Libraries. Made with the assistance of John M. Echols. Data paper: Number 62, Southeast Asia Program. Department of Asian Studies. Ithaca, Cornell University, 1966. 62 pages. - R.E. Downs, P. Middelkoop, Headhunting in Timor and its historical implications. Oceania Linguistic Monograph No. 8. The Univeristy of Sydney, Sydney, 1964. 423 pp. - M.G. Swift, Rosemary Firth, Housekeeping among Malay peasants. London School of Economics Monographs on Social Anthropology, No. 7. The Athlone Press, London 1966. Pp. xiv and 242. - Umar Junus, Harsja W. Bachtiar, Negeri Taram: A Minangkabau village community in Koentjaraningrat, ed., Villages in Indonesia. Cornell University Press, Ithaca, New York, 1967. 445 pp. - William R. Roff, Judith Djamour, The Muslim matrimonial court in Singapore. London School of Economics, Monographs on Social Anthropology. No. 31. Athlone Press, London, 1966. 189 pp. - Paul Wheatley, O.W. Wolters, Early Indonesian commerce: A study of the origins of Srivijaya. Cornell University Press, Ithaca, New York, 1967. 404 pp., 4 maps. - M.P.H. Roessingh, Th. P.M. de Jong, De krimpende horizon van de Hollandse kooplieden. Hollands Welvaren in het Caribisch Zeegebied (1780-1830. Van Gorcum en Comp., Assen, 1966. 352 pp., 2 ills., 1 krt. Oorspr. proefschrift Groningen, met een voorwoord van de schrijver; tevens verschenen als Anjerpublicatie nr. 9, met een woord vooraf van de promotor, Prof. Dr. H. Baudet. - M. Leifer, James de V. Allen, The Malayan Union. Yale University, Southeast Asia Studies, 1967. Monograph Series No. 10. XIV + 181 pp., with appendices. - P. Voorhoeve, M.A. Jaspan, Folk literature of South Sumatra. Rejang Ka-Ga-Nga Texts. Australian University Press, Canberra 1964. 92 pp.
Fibroblast and keratinocyte gene expression following exposure to the extracts of holy basil plant (Ocimum tenuiflorum, malabar nut plant (Justicia adhatoda, and emblic myrobalan plant (Phyllanthus emblica
Full Text Available This data article provides gene expression profiles, determined by using real-time PCR, of fibroblasts and keratinocytes treated with 0.01% and 0.001% extracts of holy basil plant (Ocimum tenuiflorum, sri lankan local name “maduruthala”, 0.1% and 0.01% extracts of malabar nut plant (Justicia adhatoda, sri lankan local name “adayhoda” and 0.003% and 0.001% extracts of emblic myrobalan plant (Phyllanthus emblica, sri lankan local name “nelli”, harvested in Sri Lanka. For fibroblasts, the dataset includes expression profiles for genes encoding hyaluronan synthase 1 (HAS1, hyaluronan synthase 2 (HAS2, hyaluronidase-1 (HYAL1, hyaluronidase-2 (HYAL2, versican, aggrecan, CD44, collagen, type I, alpha 1 (COL1A1, collagen, type III, alpha 1 (COL3A1, collagen, type VII, alpha 1 (COL7A1, matrix metalloproteinase 1 (MMP1, acid ceramidase, basic fibroblast growth factor (bFGF, fibroblast growth factor-7 (FGF7, vascular endothelial growth factor (VEGF, interleukin-1 alpha (IL-1α, cyclooxygenase-2 (cox2, transforming growth factor beta (TGF-β, and aquaporin 3 (AQP3. For keratinocytes, the expression profiles are for genes encoding HAS1, HAS2, HYAL1, HYAL2, versican, CD44, IL-1α, cox2, TGF-β, AQP3, Laminin5, collagen, type XVII, alpha 1 (COL17A1, integrin alpha-6 (ITGA6, ceramide synthase 3 (CERS3, elongation of very long chain fatty acids protein 1 (ELOVL1, elongation of very long chain fatty acids protein 4 (ELOVL4, filaggrin (FLG, transglutaminase 1 (TGM1, and keratin 1 (KRT1. The expression profiles are provided as bar graphs. Keywords: Real-time PCR, Gene expression profile, Fibroblast, Keratinocyte, Holy basil extract, Ocimum tenuiflorum, Maduruthala, Malabar nut plant extract, Justicia adhatoda, Adayhoda, Emblic myrobalan extract, Phyllanthus emblica, Nelli
Seo, Min-Duk; Kang, Tae Jin; Lee, Chang Hoon; Lee, Ai-Young; Noh, Minsoo
HaCaT cells are the immortalized human keratinocytes and have been extensively used to study the epidermal homeostasis and its pathophysiology. T helper cells play a role in various chronic dermatological conditions and they can affect skin barrier homeostasis. To evaluate whether HaCaT cells can be used as a model cell system to study abnormal skin barrier development in various dermatologic diseases, we analyzed the gene expression profile of epidermal differentiation markers of HaCaT cells in response to major T helper (Th) cell cytokines, such as IFNγ, IL-4, IL-17A and IL-22. The gene transcriptional profile of cornified envelope-associated proteins, such as filaggrin, loricrin, involucrin and keratin 10 (KRT10), in HaCaT cells was generally different from that in normal human keratinocytes (NHKs). This suggests that HaCaT cells have a limitation as a model system to study the pathophysiological mechanism associated with the Th cell cytokine-dependent changes in cornified envelope-associated proteins which are essential for normal skin barrier development. In contrast, the gene transcription profile change of human β2-defensin (HBD2) in response to IFNγ, IL-4 or IL-17A in HaCaT cells was consistent with the expression pattern of NHKs. IFNγ also up-regulated transglutaminase 2 (TGM2) gene transcription in both HaCaT cells and NHKs. As an alternative cell culture system for NHKs, HaCaT cells can be used to study molecular mechanisms associated with abnormal HBD2 and TGM2 expression in response to IFNγ, IL-4 or IL-17A. PMID:24116291
Feeling Y Chen
Full Text Available Sjögren's syndrome (SS is a chronic, autoimmune exocrinopathy that leads to severe dryness of the mouth and eyes. Exocrine function is highly regulated by neuronal mechanisms but little is known about the link between chronic inflammation, innervation and altered exocrine function in the diseased eyes and exocrine glands of SS patients. To gain a better understanding of neuronal regulation in the immunopathogenesis of autoimmune exocrinopathy, we profiled a mouse model of spontaneous, autoimmune exocrinopathy that possess key characteristics of peripheral neuropathy experienced by SS patients. Mice deficient in the autoimmune regulator (Aire gene developed spontaneous, CD4+ T cell-mediated exocrinopathy and aqueous-deficient dry eye that were associated with loss of nerves innervating the cornea and lacrimal gland. Changes in innervation and tear secretion were accompanied by increased proliferation of corneal epithelial basal cells, limbal expansion of KRT19-positive progenitor cells, increased vascularization of the peripheral cornea and reduced nerve function in the lacrimal gland. In addition, we found extensive loss of MIST1+ secretory acinar cells in the Aire -/- lacrimal gland suggesting that acinar cells are a primary target of the disease, Finally, topical application of ophthalmic steroid effectively restored corneal innervation in Aire -/- mice thereby functionally linking nerve loss with local inflammation in the aqueous-deficient dry eye. These data provide important insight regarding the relationship between chronic inflammation and neuropathic changes in autoimmune-mediated dry eye. Peripheral neuropathies characteristic of SS appear to be tightly linked with the underlying immunopathological mechanism and Aire -/- mice provide an excellent tool to explore the interplay between SS-associated immunopathology and peripheral neuropathy.
Jin, Hee; Jeon, Seulgi; Kang, Ga-Young; Lee, Hae-June; Cho, Jaeho; Lee, Yun-Sil
The molecular effects of focal exposure of limited lung volumes to high-dose per fraction irradiation (HDFR) such as stereotactic body radiotherapy (SBRT) have not been fully characterized. In this study, we used such an irradiation system and identified the genes and proteins after HDFR to mouse lung, similar to those associated with human therapy. High focal radiation (90 Gy) was applied to a 3-mm volume of the left lung of C57BL6 mice using a small-animal stereotactic irradiator. As well as histological examination for lungs, a cDNA micro array using irradiated lung tissues and a protein array of sera were performed until 4 weeks after irradiation, and radiation-responsive genes and proteins were identified. For comparison, the long-term effects (12 months) of 20 Gy radiation wide-field dose to the left lung were also investigated. The genes ermap, epb4.2, cd200r3 (up regulation) and krt15, hoxc4, gdf2, cst9, cidec, and bnc1 (down-regulation) and the proteins of AIF, laminin, bNOS, HSP27, β-amyloid (upregulation), and calponin (downregulation) were identified as being responsive to 90 Gy HDFR. The gdf2, cst9, and cidec genes also responded to 20 Gy, suggesting that they are universal responsive genes in irradiated lungs. No universal proteins were identified in both 90 Gy and 20 Gy. Calponin, which was downregulated in protein antibody array analysis, showed a similar pattern in microarray data, suggesting a possible HDFR responsive serum biomarker that reflects gene alteration of irradiated lung tissue. These genes and proteins also responded to the lower doses of 20 Gy and 50 Gy HDFR. These results suggest that identified candidate genes and proteins are HDFR-specifically expressed in lung damage induced by HDFR relevant to SBRT in humans.
Wild, P J; Catto, J W F; Abbod, M F; Linkens, D A; Herr, A; Pilarsky, C; Wissmann, C; Stoehr, R; Denzinger, S; Knuechel, R; Hamdy, F C; Hartmann, A
Non-muscle invasive bladder cancer is a heterogenous disease whose management is dependent upon the risk of progression to muscle invasion. Although the recurrence rate is high, the majority of tumors are indolent and can be managed by endoscopic means alone. The prognosis of muscle invasion is poor and radical treatment is required if cure is to be obtained. Progression risk in non-invasive tumors is hard to determine at tumor diagnosis using current clinicopathological means. To improve the accuracy of progression prediction various biomarkers have been evaluated. To discover novel biomarkers several authors have used gene expression microarrays. Various statistical methods have been described to interpret array data, but to date no biomarkers have entered clinical practice. Here, we describe a new method of microarray analysis using neurofuzzy modeling (NFM), a form of artificial intelligence, and integrate it with artificial neural networks (ANN) to investigate non-muscle invasive bladder cancer array data (n=66 tumors). We develop a predictive panel of 11 genes, from 2800 expressed genes, that can significantly identify tumor progression (average Logrank p = 0.0288) in the analyzed cancers. In comparison, this panel appears superior to those genes chosen using traditional analyses (average Logrank p = 0.3455) and tumor grade (Logrank, p = 0.2475) in this non-muscle invasive cohort. We then analyze panel members in a new non-muscle invasive bladder cancer cohort (n=199) using immunohistochemistry with six commercially available antibodies. The combination of 6 genes (LIG3, TNFRSF6, KRT18, ICAM1, DSG2 and BRCA2) significantly stratifies tumor progression (Logrank p = 0.0096) in the new cohort. We discuss the benefits of the transparent NFM approach with respect to other reported methods.
Thompson, Loren P; Pence, Laramie; Pinkas, Gerald; Song, Hong; Telugu, Bhanu P
Chronic placental hypoxia is one of the root causes of placental insufficiencies that result in pre-eclampsia and maternal hypertension. Chronic hypoxia causes disruption of trophoblast (TB) development, invasion into maternal decidua, and remodeling of maternal spiral arteries. The pregnant guinea pig shares several characteristics with humans such as hemomonochorial placenta, villous subplacenta, deep TB invasion, and remodeling of maternal arteries, and is an ideal animal model to study placental development. We hypothesized that chronic placental hypoxia of the pregnant guinea pig inhibits TB invasion and alters spiral artery remodeling. Time-mated pregnant guinea pigs were exposed to either normoxia (NMX) or three levels of hypoxia (HPX: 16%, 12%, or 10.5% O 2 ) from 20 day gestation until midterm (39-40 days) or term (60-65 days). At term, HPX (10.5% O 2 ) increased maternal arterial blood pressure (HPX 57.9 ± 2.3 vs. NMX 40.4 ± 2.3, P < 0.001), decreased fetal weight by 16.1% (P < 0.05), and increased both absolute and relative placenta weights by 10.1% and 31.8%, respectively (P < 0.05). At midterm, there was a significant increase in TB proliferation in HPX placentas as confirmed by increased PCNA and KRT7 staining and elevated ESX1 (TB marker) gene expression (P < 0.05). Additionally, quantitative image analysis revealed decreased invasion of maternal blood vessels by TB cells. In summary, this animal model of placental HPX identifies several aspects of abnormal placental development, including increased TB proliferation and decreased migration and invasion of TBs into the spiral arteries, the consequences of which are associated with maternal hypertension and fetal growth restriction. © 2016 by the Society for the Study of Reproduction, Inc.
Seol, Min-A; Kim, Dae-Ghon; Chu, In-Sun; Lee, Mi-Jin; Yu, Goung-Ran; Cui, Xiang-Dan; Cho, Baik-Hwan; Ahn, Eun-Kyung; Leem, Sun-Hee; Kim, In-Hee
The molecular mechanisms of CC (cholangiocarcinoma) oncogenesis and progression are poorly understood. This study aimed to determine the genome-wide expression of genes related to CC oncogenesis and sarcomatous transdifferentiation. Genes that were differentially expressed between CC cell lines or tissues and cultured normal biliary epithelial (NBE) cells were identified using DNA microarray technology. Expressions were validated in human CC tissues and cells. Using unsupervised hierarchical clustering analysis of the cell line and tissue samples, we identified a set of 342 commonly regulated (>2-fold change) genes. Of these, 53, including tumor-related genes, were upregulated, and 289, including tumor suppressor genes, were downregulated (<0.5 fold change). Expression of SPP1, EFNB2, E2F2, IRX3, PTTG1, PPARγ, KRT17, UCHL1, IGFBP7 and SPARC proteins was immunohistochemically verified in human and hamster CC tissues. Additional unsupervised hierarchical clustering analysis of sarcomatoid CC cells compared to three adenocarcinomatous CC cell lines revealed 292 differentially upregulated genes (>4-fold change), and 267 differentially downregulated genes (<0.25 fold change). The expression of 12 proteins was validated in the CC cell lines by immunoblot analysis and immunohistochemical staining. Of the proteins analyzed, we found upregulation of the expression of the epithelial-mesenchymal transition (EMT)-related proteins VIM and TWIST1, and restoration of the methylation-silenced proteins LDHB, BNIP3, UCHL1, and NPTX2 during sarcomatoid transdifferentiation of CC. The deregulation of oncogenes, tumor suppressor genes, and methylation-related genes may be useful in identifying molecular targets for CC diagnosis and prognosis
Liu, G.; Li, D.Z.; Jiang, C.S.; Wang, W. [Fuzhou General Hospital of Nanjing Command, Department of Gastroenterology, Fuzhou, China, Department of Gastroenterology, Fuzhou General Hospital of Nanjing Command, Fuzhou (China)
To investigate signal regulation models of gastric cancer, databases and literature were used to construct the signaling network in humans. Topological characteristics of the network were analyzed by CytoScape. After marking gastric cancer-related genes extracted from the CancerResource, GeneRIF, and COSMIC databases, the FANMOD software was used for the mining of gastric cancer-related motifs in a network with three vertices. The significant motif difference method was adopted to identify significantly different motifs in the normal and cancer states. Finally, we conducted a series of analyses of the significantly different motifs, including gene ontology, function annotation of genes, and model classification. A human signaling network was constructed, with 1643 nodes and 5089 regulating interactions. The network was configured to have the characteristics of other biological networks. There were 57,942 motifs marked with gastric cancer-related genes out of a total of 69,492 motifs, and 264 motifs were selected as significantly different motifs by calculating the significant motif difference (SMD) scores. Genes in significantly different motifs were mainly enriched in functions associated with cancer genesis, such as regulation of cell death, amino acid phosphorylation of proteins, and intracellular signaling cascades. The top five significantly different motifs were mainly cascade and positive feedback types. Almost all genes in the five motifs were cancer related, including EPOR, MAPK14, BCL2L1, KRT18, PTPN6, CASP3, TGFBR2, AR, and CASP7. The development of cancer might be curbed by inhibiting signal transductions upstream and downstream of the selected motifs.
Lindberg, Mallory E.; Stodden, Genna R.; King, Mandy L.; MacLean, James A.; Mann, Jordan L.; DeMayo, Francesco J.; Lydon, John P.; Hayashi, Kanako
ABSTRACT E-cadherin (CDH1) is a cell adhesion molecule that coordinates key morphogenetic processes regulating cell growth, cell proliferation, and apoptosis. Loss of CDH1 is a trademark of the cellular event epithelial to mesenchymal transition, which increases the metastatic potential of malignant cells. PTEN is a tumor-suppressor gene commonly mutated in many human cancers, including endometrial cancer. In the mouse uterus, ablation of Pten induces epithelial hyperplasia, leading to endometrial carcinomas. However, loss of Pten alone does not affect longevity until around 5 mo. Similarly, conditional ablation of Cdh1 alone does not predispose mice to cancer. In this study, we characterized the impact of dual Cdh1 and Pten ablation (Cdh1d/d Ptend/d) in the mouse uterus. We observed that Cdh1d/d Ptend/d mice died at Postnatal Days 15–19 with massive blood loss. Their uteri were abnormally structured with curly horns, disorganized epithelial structure, and increased cell proliferation. Co-immunostaining of KRT8 and ACTA2 showed invasion of epithelial cells into the myometrium. Further, the uteri of Cdh1d/d Ptend/d mice had prevalent vascularization in both the endometrium and myometrium. We also observed reduced expression of estrogen and progesterone receptors, loss of cell adherens, and tight junction molecules (CTNNB1 and claudin), as well as activation of AKT in the uteri of Cdh1d/d Ptend/d mice. However, complex hyperplasia was not found in the uteri of Cdh1d/d Ptend/d mice. Collectively, these findings suggest that ablation of Pten with Cdh1 in the uterus accelerates cellular invasiveness and angiogenesis and causes early death. PMID:23740945
Lindberg, Mallory E; Stodden, Genna R; King, Mandy L; MacLean, James A; Mann, Jordan L; DeMayo, Francesco J; Lydon, John P; Hayashi, Kanako
E-cadherin (CDH1) is a cell adhesion molecule that coordinates key morphogenetic processes regulating cell growth, cell proliferation, and apoptosis. Loss of CDH1 is a trademark of the cellular event epithelial to mesenchymal transition, which increases the metastatic potential of malignant cells. PTEN is a tumor-suppressor gene commonly mutated in many human cancers, including endometrial cancer. In the mouse uterus, ablation of Pten induces epithelial hyperplasia, leading to endometrial carcinomas. However, loss of Pten alone does not affect longevity until around 5 mo. Similarly, conditional ablation of Cdh1 alone does not predispose mice to cancer. In this study, we characterized the impact of dual Cdh1 and Pten ablation (Cdh1(d/d) Pten(d/d)) in the mouse uterus. We observed that Cdh1(d/d) Pten(d/d) mice died at Postnatal Days 15-19 with massive blood loss. Their uteri were abnormally structured with curly horns, disorganized epithelial structure, and increased cell proliferation. Co-immunostaining of KRT8 and ACTA2 showed invasion of epithelial cells into the myometrium. Further, the uteri of Cdh1(d/d) Pten(d/d) mice had prevalent vascularization in both the endometrium and myometrium. We also observed reduced expression of estrogen and progesterone receptors, loss of cell adherens, and tight junction molecules (CTNNB1 and claudin), as well as activation of AKT in the uteri of Cdh1(d/d) Pten(d/d) mice. However, complex hyperplasia was not found in the uteri of Cdh1(d/d) Pten(d/d) mice. Collectively, these findings suggest that ablation of Pten with Cdh1 in the uterus accelerates cellular invasiveness and angiogenesis and causes early death.
Hoelker, Michael; Rings, Franka; Lund, Qamaruddin; Ghanem, Nasser; Phatsara, Chirawath; Griese, Josef; Schellander, Karl; Tesfaye, Dawit
The Well of the Well (WOW) system has been developed to culture embryos in small groups or to track the development of single embryos. In the present study, we aimed to examine the effects of the microenvironment provided by the WOW system and embryo density on developmental rates, embryo quality and preimplantative gene expression profile of the resulting embryos. Embryos cultured in a group of 16 reached the blastocyst stage at a significantly lower level than zygotes cultured in a group of 50 (22.2 vs 30.3%), whereas zygotes cultured in WOW were able to compensate against low embryo densities, reaching a blastocyst rate as high as embryos cultured in a group of 50 (31.3 vs 30.3%). Moreover, embryos derived from WOW culture did not differ in terms of differential cell counts and apoptotic cell index compared with controls. The gene expression analysis revealed 62 transcripts to be upregulated and 33 transcripts to be downregulated by WOW culture. Comparing the in vivo derived blastocysts with the blastocysts derived from WOW culture, and group culture, expression of ATP5A1, PLAC8 and KRT8 was more similar to the embryos derived from WOW culture, whereas expression of S100A10 and ZP3 genes was more similar to blastocysts cultured in a group. In conclusion, microenvironment as well as embryo density significantly affected developmental rates. While subsequent blastocysts did not differ in terms of differential cell counts and apoptotic cell index, significant differences were observed in terms of the relative abundance of transcripts in the resulting embryos.
Full Text Available Boar taint is an unpleasant smell and taste of pork meat derived from some entire male pigs. The main causes of boar taint are the two compounds androstenone (5α-androst-16-en-3-one and skatole (3-methylindole. It is crucial to understand the genetic mechanism of boar taint to select pigs for lower androstenone levels and thus reduce boar taint. The aim of the present study was to investigate transcriptome differences in boar testis and liver tissues with divergent androstenone levels using RNA deep sequencing (RNA-Seq. The total number of reads produced for each testis and liver sample ranged from 13,221,550 to 33,206,723 and 12,755,487 to 46,050,468, respectively. In testis samples 46 genes were differentially regulated whereas 25 genes showed differential expression in the liver. The fold change values ranged from -4.68 to 2.90 in testis samples and -2.86 to 3.89 in liver samples. Differentially regulated genes in high androstenone testis and liver samples were enriched in metabolic processes such as lipid metabolism, small molecule biochemistry and molecular transport. This study provides evidence for transcriptome profile and gene polymorphisms of boars with divergent androstenone level using RNA-Seq technology. Digital gene expression analysis identified candidate genes in flavin monooxygenease family, cytochrome P450 family and hydroxysteroid dehydrogenase family. Moreover, polymorphism and association analysis revealed mutation in IRG6, MX1, IFIT2, CYP7A1, FMO5 and KRT18 genes could be potential candidate markers for androstenone levels in boars. Further studies are required for proving the role of candidate genes to be used in genomic selection against boar taint in pig breeding programs.
Mego, M.; Cierna, Z.; Janega, P.; Karaba, M.; Minarik, G.; Benca, J.; Sedlácková, T.; Sieberova, G.; Gronesova, P.; Manasova, D.; Pindak, D.; Sufliarsky, J.; Danihel, L.; Reuben, JM; Mardiak, J.
Circulating tumor cells (CTCs) play a crucial role in tumor dissemination and are an independent survival predictor in breast cancer (BC) patients. Epithelial to mesenchymal transition (EMT) is involved in cancer invasion and metastasis. The aim of this study was to assess correlation between CTCs and expression of EMT transcription factors TWIST1 and SLUG in breast tumor tissue. This study included 102 early BC patients treated by primary surgery. Peripheral blood mononuclear cells (PBMC) were depleted of hematopoietic cells using RossetteSep™ negative selection kit. RNA extracted from CD45-depleted PBMC was interrogated for expression of EMT (TWIST1, SNAIL1, SLUG, FOXC2 and ZEB1) and epithelial (KRT19) gene transcripts by qRT-PCR. Expression of TWIST1 and SLUG in surgical specimens was evaluated by immunohistochemistry and quantified by multiplicative score. CTCs were detected in 24.5 % patients. CTCs exhibiting only epithelial markers were present in 8.8 % patients, whereas CTCs with only EMT markers were observed in 12.8 % of pts and CTCs co-expressing both markers were detected in 2.9 % pts. We observed lack of correlation between CTCs and expression of TWIST1 and SLUG in breast cancer cells or cancer associated stroma. Lack of correlation was observed for epithelial CTCs as well as for CTCs with EMT. In this translational study, we showed a lack of association between CTCs and expression of EMT-inducing transcription factors, TWIST1 and SLUG, in breast tumor tissue. Despite the fact that EMT is involved in cancer invasion and metastasis our results suggest, that expression of EMT proteins in unselected tumor tissue is not surrogate marker of CTCs with either mesenchymal or epithelial features
Tao, Yiqing; Zhou, Xiaopeng; Liu, Dongyu; Li, Hao; Liang, Chengzhen; Li, Fangcai; Chen, Qixin
During degeneration process, the catabolism of collagen type II and anabolism of collagen type I in nucleus pulposus (NP) may influence the bioactivity of transplanted cells. Human adipose-derived mesenchymal stem cells (hADMSCs) were cultured as a micromass or in a series of gradual proportion hydrogels of a mix of collagen types I and II. Cell proliferation and cytotoxicity were detected using CCK-8 and LDH assays respectively. The expression of differentiation-related genes and proteins, including SOX9, aggrecan, collagen type I, and collagen type II, was examined using RT-qPCR and Western blotting. Novel phenotypic genes were also detected by RT-qPCR and western blotting. Alcian blue and dimethylmethylene blue assays were used to investigate sulfate proteoglycan expression, and PI3K/AKT, MAPK/ERK, and Smad signaling pathways were examined by Western blotting. The results showed collagen hydrogels have good biocompatibility, and cell proliferation increased after collagen type II treatment. Expressions of SOX9, aggrecan, and collagen type II were increased in a collagen type II dependent manner. Sulfate proteoglycan synthesis increased in proportion to collagen type II concentration. Only hADMSCs highly expressed NP cell marker KRT19 in collagen type II culture. Additionally, phosphorylated Smad3, which is associated with phosphorylated ERK, was increased after collagen type II-stimulation. The concentration and type of collagen affect hADMSC differentiation into NP cells. Collagen type II significantly ameliorates hADMSC differentiation into NP cells and promotes extracellular matrix synthesis. Therefore, anabolism of collagen type I and catabolism of type II may attenuate the differentiation and biosynthesis of transplanted stem cells. © 2016 International Union of Biochemistry and Molecular Biology.
Janice E Drew
Full Text Available Cancers exhibit abnormal molecular signatures associated with disease initiation and progression. Molecular signatures could improve cancer screening, detection, drug development and selection of appropriate drug therapies for individual patients. Typically only very small amounts of tissue are available from patients for analysis and biopsy samples exhibit broad heterogeneity that cannot be captured using a single marker. This report details application of an in-house custom designed GenomeLab System multiplex gene expression assay, the hCellMarkerPlex, to assess predictive gene signatures of normal, adenomatous polyp and carcinoma colon tissue using archived tissue bank material. The hCellMarkerPlex incorporates twenty-one gene markers: epithelial (EZR, KRT18, NOX1, SLC9A2, proliferation (PCNA, CCND1, MS4A12, differentiation (B4GANLT2, CDX1, CDX2, apoptotic (CASP3, NOX1, NTN1, fibroblast (FSP1, COL1A1, structural (ACTG2, CNN1, DES, gene transcription (HDAC1, stem cell (LGR5, endothelial (VWF and mucin production (MUC2. Gene signatures distinguished normal, adenomatous polyp and carcinoma. Individual gene targets significantly contributing to molecular tissue types, classifier genes, were further characterised using real-time PCR, in-situ hybridisation and immunohistochemistry revealing aberrant epithelial expression of MS4A12, LGR5 CDX2, NOX1 and SLC9A2 prior to development of carcinoma. Identified gene signatures identify aberrant epithelial expression of genes prior to cancer development using in-house custom designed gene expression multiplex assays. This approach may be used to assist in objective classification of disease initiation, staging, progression and therapeutic responses using biopsy material.
Full Text Available BACKGROUND: Keratins 8 and 18 (K8/K18 are intermediate filament proteins that protect the liver from various forms of injury. Exonic K8/K18 variants associate with adverse outcome in acute liver failure and with liver fibrosis progression in patients with chronic hepatitis C infection or primary biliary cirrhosis. Given the association of K8/K18 variants with end-stage liver disease and progression in several chronic liver disorders, we studied the importance of keratin variants in patients with hemochromatosis. METHODS: The entire K8/K18 exonic regions were analyzed in 162 hemochromatosis patients carrying homozygous C282Y HFE (hemochromatosis gene mutations. 234 liver-healthy subjects were used as controls. Exonic regions were PCR-amplified and analyzed using denaturing high-performance liquid chromatography and DNA sequencing. Previously-generated transgenic mice overexpressing K8 G62C were studied for their susceptibility to iron overload. Susceptibility to iron toxicity of primary hepatocytes that express K8 wild-type and G62C was also assessed. RESULTS: We identified amino-acid-altering keratin heterozygous variants in 10 of 162 hemochromatosis patients (6.2% and non-coding heterozygous variants in 6 additional patients (3.7%. Two novel K8 variants (Q169E/R275W were found. K8 R341H was the most common amino-acid altering variant (4 patients, and exclusively associated with an intronic KRT8 IVS7+10delC deletion. Intronic, but not amino-acid-altering variants associated with the development of liver fibrosis. In mice, or ex vivo, the K8 G62C variant did not affect iron-accumulation in response to iron-rich diet or the extent of iron-induced hepatocellular injury. CONCLUSION: In patients with hemochromatosis, intronic but not exonic K8/K18 variants associate with liver fibrosis development.
Full Text Available The Objective of this study is to analyze the subject research in order to construct a map of energy research conducted by R & D Institutions and university student in Indonesia. The method of the study uses Bibliometrics by collecting the data from 1998-2008. The data analyze throughout document mapping in co-word. The data result in energy sector that carried out by the R & D Institutions and the university is: 328 titles of thesis and 345 titles of research reports. Based on the collected data, there is a significant increasing in the research development from 1998 until 2008, except in 1999 which decrease from 1998 and 2004 decrease from 2003. The title numbers of university thesis from the highest are ITB, ITS, UGM, UNIBRAW, UI, UNSRI, USU, and another collections from other university are from PDII-LIPI. The title numbers of research institute are: Department of ESDM, LIPI, BATAN, KRT, and LAPAN. The research are focused on: biofuel, electricity energy, solar energy, coals, fuel energy, nuclear energy, wind energy, petroleum and natural gas, geothermal energy, bio mass and biogas, sea current and sea wave, steam energy, and hydrogen/fuel cell, whereas under the 10 research titles there are a lot of kinds of energy such as gas, earth gas, steam, and alternative energies, and others focuses. This study concludes that there are 46 topics which conducted research by university as well as R & D Institutions. The output of this study is database, containing of 960 records of energy research. The result shows the differences of mapping for energy research. This research recommends the need of documentation system policy on grey literature especially on energy research.
Kantaputra, Piranit Nik; Kapoor, Seema; Verma, Prashant; Kaewgahya, Massupa; Kawasaki, Katsushige; Ohazama, Atsushi; Ketudat Cairns, James R
Al-Awadi-Raas-Rothschild syndrome (AARRS; OMIM 276820) is a very rare autosomal recessive limb malformation syndrome caused by WNT7A mutations. AARRS is characterized by various degrees of limb aplasia and hypoplasia. Normal intelligence and malformations of urogenital system are frequent findings. Complete loss of WNT7A function has been shown to cause AARRS, however, its partial loss leads to the milder malformation, Fuhrmann syndrome. An Indian boy affected with AARRS is reported. A novel homozygous base substitution mutation c.550A > C (p.Asn184Asp) is identified in the patient. Parents were heterozygous for the mutation. In addition to the typical features of AARRS, the patient had agenesis of the mandibular left deciduous lateral incisor. The heterozygous parents had microdontia of the maxillary left permanent third molar and taurodontism (enlarged dental pulp chamber at the expense of root) in a number of their permanent molars. Whole exome sequencing of the patient and his parents ruled out mutations in 11 known hypodontia-associated genes including WNT10A, MSX1, EDA, EDAR, EDARADD, PAX9, AXIN2, GREM2, NEMO, KRT17, and TFAP2B. In situ hybridization during tooth development showed Wnt7a expression in wild-type tooth epithelium at E14.5. All lines of evidence suggest that WNT7A has important role in tooth development and its mutation may lead to tooth agenesis, microdontia, and taurodontism. Oral examination of patients with AARRS and Fuhrmann syndromes is highly recommended. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Wertheimer Michael R
Full Text Available Abstract Background The loss of the notochordal cells from the nucleus pulposus is associated with ageing and disc degeneration. However, understanding the mechanisms responsible for the loss of these cells has been hampered in part due to the difficulty of culturing and maintaining their phenotype. Furthermore, little is known about the influence of the substratum on the molecular markers of notochordal cells. Methods Notochordal cells were isolated from lumbar spine of non-chondrodystrophoid dogs and cultured on N-rich plasma polymer layers, so-called "PPE:N" (N-doped plasma-polymerised ethylene, containing up to 36% [N] surfaces, for 3, 7 or 14 days. Gene expression of vimentin (VIM, pleiotrophin (PTN, matrix Gla protein (MGP, cartilage oligomeric matrix protein (COMP, keratin 18 (KRT 18, aggrecan (AGG, collagen type 1 (COL1A2, collagen type 2 (COL2A1 was analyzed through semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR. Results Notochordal cells were maintained in culture on PPE:N for up to 14 days with no loss in cell viability. Except for VIM, gene expression varied depending on the culture periods and [N] concentration of the substratum. Generally, PPE:N surfaces altered gene expression significantly when cells were cultured for 3 or 7 days. Conclusion The present study has shown that notochordal cells from dogs can attach to and grow on PPE:N surfaces. Analysis of the expression of different genes in these cells cultured on different N-functionalized surfaces indicates that cellular behaviour is gene-specific and time-dependent. Further studies are required to better understand the roles of specific surface functionalities on receptor sites, and their effects on cellular phenotypes.
Full Text Available We aimed to assess whether pri-miRNA SNPs (miSNPs could influence monocyte gene expression, either through marginal association or by interacting with polymorphisms located in 3'UTR regions (3utrSNPs. We then conducted a genome-wide search for marginal miSNPs effects and pairwise miSNPs × 3utrSNPs interactions in a sample of 1,467 individuals for which genome-wide monocyte expression and genotype data were available. Statistical associations that survived multiple testing correction were tested for replication in an independent sample of 758 individuals with both monocyte gene expression and genotype data. In both studies, the hsa-mir-1279 rs1463335 was found to modulate in cis the expression of LYZ and in trans the expression of CNTN6, CTRC, COPZ2, KRT9, LRRFIP1, NOD1, PCDHA6, ST5 and TRAF3IP2 genes, supporting the role of hsa-mir-1279 as a regulator of several genes in monocytes. In addition, we identified two robust miSNPs × 3utrSNPs interactions, one involving HLA-DPB1 rs1042448 and hsa-mir-219-1 rs107822, the second the H1F0 rs1894644 and hsa-mir-659 rs5750504, modulating the expression of the associated genes.As some of the aforementioned genes have previously been reported to reside at disease-associated loci, our findings provide novel arguments supporting the hypothesis that the genetic variability of miRNAs could also contribute to the susceptibility to human diseases.
Therkildsen, Christina; Eriksson, Pontus; Höglund, Mattias; Jönsson, Mats; Sjödahl, Gottfrid; Nilbert, Mef; Liedberg, Fredrik
Lynch syndrome confers an increased risk for urothelial carcinoma (UC). Molecular subtypes may be relevant to prognosis and therapeutic possibilities, but have to date not been defined in Lynch syndrome-associated urothelial cancer. We aimed to provide a molecular description of Lynch syndrome-associated UC. Thus, Lynch syndrome-associated UC of the upper urinary tract and the urinary bladder were identified in the Danish hereditary non-polyposis colorectal cancer (HNPCC) register and were transcriptionally and immunohistochemically profiled and further related to data from 307 sporadic urothelial carcinomas. Whole genome mRNA expression profiles of 41 tumors and immunohistochemical stainings against FGFR3, KRT5, CCNB1, RB1, and CDKN2A (p16) of 37 tumors from Lynch syndrome patients were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data was analyzed and compared with sporadic bladder cancer. The 41 Lynch syndrome-associated UC developed at a mean age of 61 years with 59% women. mRNA expression profiling and immunostaining classified the majority of the Lynch syndrome-associated UC as Urothelial-like tumors with only 20% being Genomically Unstable, Basal/SCC-like or other subtypes. The subtypes were associated with stage, grade, and microsatellite instability. Comparison to larger data sets revealed that Lynch syndrome-associated UC share molecular similarities with sporadic UC. In conclusion, transcriptomic and immunohistochemical profiling identifies a predominance of the Urothelial-like molecular subtype in Lynch syndrome and reveals that the molecular subtypes of sporadic bladder cancer are relevant also within this hereditary, mismatch-repair defective subset. This article is protected by copyright. All rights reserved. Molecular Oncology (2018) © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.
Diaz Rua, Ruben; Van Schothorst, E. M.; Keijer, J.; Palou, A.; Oliver, P.
Background/Objectives: Consumption of fat-rich foods is associated with obesity and related alterations. However, there is a group of individuals, the metabolically obese normal-weight (MONW) subjects, who present normal body weight but have metabolic features characteristic of the obese status, including fat deposition in critical tissues such as liver, recognized as a major cause for the promotion of metabolic diseases. Our aim was to better understand metabolic alterations present in liver of MONW rats applying whole genome transcriptome analysis. Methods: Wistar rats were chronically fed a high-fat diet isocaloric relative to Control animals to avoid the hyperphagia and overweight and to mimic MONW features. Liver transcriptome analysis of both groups was performed. Results: Sustained intake of an isocaloric high-fat diet had a deep impact on the liver transcriptome, mainly affecting lipid metabolism. Although serum cholesterol levels were not affected, circulating triacylglycerols were lower, and metabolic adaptations at gene expression level indicated adaptation toward handling the increased fat content of the diet, an increased triacylglycerol and cholesterol deposition in liver of MONW rats was observed. Moreover, gene expression pointed to increased risk of liver injury. One of the top upregulated genes in this tissue was Krt23, a marker of hepatic disease in humans that was also increased at the protein level.Conclusion:Long-term intake of a high-fat diet, even in the absence of overweight/obesity or increase in classical blood risk biomarkers, promotes a molecular environment leading to hepatic lipid accumulation and increasing the risk of suffering from hepatic diseases.
Diaz Rua, Ruben
Background/Objectives: Consumption of fat-rich foods is associated with obesity and related alterations. However, there is a group of individuals, the metabolically obese normal-weight (MONW) subjects, who present normal body weight but have metabolic features characteristic of the obese status, including fat deposition in critical tissues such as liver, recognized as a major cause for the promotion of metabolic diseases. Our aim was to better understand metabolic alterations present in liver of MONW rats applying whole genome transcriptome analysis. Methods: Wistar rats were chronically fed a high-fat diet isocaloric relative to Control animals to avoid the hyperphagia and overweight and to mimic MONW features. Liver transcriptome analysis of both groups was performed. Results: Sustained intake of an isocaloric high-fat diet had a deep impact on the liver transcriptome, mainly affecting lipid metabolism. Although serum cholesterol levels were not affected, circulating triacylglycerols were lower, and metabolic adaptations at gene expression level indicated adaptation toward handling the increased fat content of the diet, an increased triacylglycerol and cholesterol deposition in liver of MONW rats was observed. Moreover, gene expression pointed to increased risk of liver injury. One of the top upregulated genes in this tissue was Krt23, a marker of hepatic disease in humans that was also increased at the protein level.Conclusion:Long-term intake of a high-fat diet, even in the absence of overweight/obesity or increase in classical blood risk biomarkers, promotes a molecular environment leading to hepatic lipid accumulation and increasing the risk of suffering from hepatic diseases.
Chen, Feeling Y; Lee, Albert; Ge, Shaokui; Nathan, Sara; Knox, Sarah M; McNamara, Nancy A
Sjögren's syndrome (SS) is a chronic, autoimmune exocrinopathy that leads to severe dryness of the mouth and eyes. Exocrine function is highly regulated by neuronal mechanisms but little is known about the link between chronic inflammation, innervation and altered exocrine function in the diseased eyes and exocrine glands of SS patients. To gain a better understanding of neuronal regulation in the immunopathogenesis of autoimmune exocrinopathy, we profiled a mouse model of spontaneous, autoimmune exocrinopathy that possess key characteristics of peripheral neuropathy experienced by SS patients. Mice deficient in the autoimmune regulator (Aire) gene developed spontaneous, CD4+ T cell-mediated exocrinopathy and aqueous-deficient dry eye that were associated with loss of nerves innervating the cornea and lacrimal gland. Changes in innervation and tear secretion were accompanied by increased proliferation of corneal epithelial basal cells, limbal expansion of KRT19-positive progenitor cells, increased vascularization of the peripheral cornea and reduced nerve function in the lacrimal gland. In addition, we found extensive loss of MIST1+ secretory acinar cells in the Aire -/- lacrimal gland suggesting that acinar cells are a primary target of the disease, Finally, topical application of ophthalmic steroid effectively restored corneal innervation in Aire -/- mice thereby functionally linking nerve loss with local inflammation in the aqueous-deficient dry eye. These data provide important insight regarding the relationship between chronic inflammation and neuropathic changes in autoimmune-mediated dry eye. Peripheral neuropathies characteristic of SS appear to be tightly linked with the underlying immunopathological mechanism and Aire -/- mice provide an excellent tool to explore the interplay between SS-associated immunopathology and peripheral neuropathy.
Full Text Available Hvorfor vurderer så mange kokker å skifte yrke når det samtidig viser seg at mange også er stolte av yrket sitt (Spetalen, Eben & Jahnlu, 2016; St. Olav Hospital, 2013, Tidemann & Myklebust, 2005? Denne artikkelen vil rette oppmerksomheten på mulige årsaker til dette, og hvorfor restaurantkokker vurderer å endre arbeidsplass eller yrkesmulighet. Restaurantbransjen er i rask utvikling og befolkningen spiser stadig oftere på restaurant (Bugge & Lavik, 2007. Samtidig synker rekruteringen til kokkeyrket (Sundquist, 2016. Det er derfor viktig å drøfte hvilke faktorer som har betydning for at restaurantkokker forlater yrket etter forholdsvis kort tid.Problemstillingen er; Hvorfor vurderer så mange kokker å skifte yrke når de er så stolte av yrket sitt?I denne artikkelen er det gjennomført en reanalyse av grunnlagsmaterialet som ble presentert i rapporten «Yrkesutøvelse i restaurant og matfagene – Arbeidsoppgaver, prioriteringer og forskjeller» (Spetalen, Eben & Jahnlu, 2016. I tillegg til denne univariate analysen har jeg også sammenliknet gjennomsnitt og testet hypoteser ved hjelp av T-test og ANOVA i SPSS (Johannessen, 2009; Pallant, 2013. Studenter ved bachelorutdanningen i Restaurant og matfag, kull 2013 ved Høgskolen i Oslo og Akershus, tok utgangspunkt i dataene fra Spetalen et al. (2016 i sine bacheloroppgaver. I samarbeid med tre studenter er det gjennomført kvalitative intervjuer med til sammen 23 nåværende og tidligere kokker. For å forklare dataene har jeg trukket inn det organisasjonsteoretiske begrepet «turnover» siden dette er et tydelig problem i restaurantbransjen. Faktorer som tiltrekker og frastøter medarbeideren i forhold til yrket, er også med i diskusjonen for å forklare funnene (Lashley, 2000; Brochs-Haukedal, 2010; Kuvås, 2013. Med bakgrunn i funnene fra de kvalitative intervjuene kan man anta at følgende årsaker veier tungt når kokker aktivt søker annen yrkeskarriere:Ledelse – mangel p
Løvhøiden, G.; Thorsteinsen, T. F.; Vaagen, J. S.
Humanities (NAVF), The Norwegian Physical Society, The Community of Karmøy, Hydro Aluminium Karmøy, Statoil, Laborel, Aanderaa Instruments and also by other local firms and institutions. The financial as well as practical support from all of these sources is gratefully acknowledged. We will in particular express our appreciation for the indispensable help from cand. real. Konrad Bardsen and his colleagues at the gymnasium where the daily scientific activity, and also major parts of the social program, took place. The meeting could not have been organized nor carried through without the professional help from Karen-Margrete Hovland, backed by her sister Alice and a team of hard-working graduate students from Bergen: Erling Andersen, Håvard Helstrup, Torbjørn Rogde and Espen Staubo. We thank all of our speakers for a smooth cooperation. * The logo of the meeting, Seidmennene på Skrattaskjaer (Old Norse: seidmann = "shaman", skrattasker = wizard or troll skerry) has resulted in colorful interpretations and comments. The organizing committee noticed, with satisfaction, that the logo had been correctly identified in one of the contributions. The still curious reader may read about this thousand year old historic event in the sagas of the NORSE KINGS by Snorri Sturluson, in the saga of Olav Trygvason.
E.Ch.L. van der Vliet
Full Text Available - Rita Bolland, Alfred Bühler, The patola of Gujarat. Double ikat in India. Krebs AG Basel, 1979. Vol. 1, 360 p. tekst, ill. Vol. 2, afb. in kleur en zwart/wit, krt. tab. noten, verkl. woorden. litl., Eberhard Fischer (eds. - Raymond Buve, Hugo G. Nutini, Ritual kinship. The structure and historical development of the Compadrazgo system in rural Tlaxcala, Vol. I. Princeton University Press, N.J., 1980, XVI plus 494 pp., maps, tables, glossary and index., Betty Bell (eds. - Benno Galjart, G.A. Banck, Jagen met een kat... Schaarse middelen en sociale relaties in de Braziliaanse staat Espirito Santo, CEDLA Incidentele publicaties no. 8, CEDLA, Amsterdam 1977. - R.A.L.H. Gunawardana, J. van Goor, Jan Kompanie as schoolmaster: Dutch education in Ceylon, 1690-1795, Historische Studies, Instituut voor Geschiedenis der Rijksuniversiteit te Utrecht, XXIV, Wolters-Noordhoff Groningen, 1978, 205 pp., 3 maps. - Ria Kloppenborg, R.A.L.H. Gunawardana, Robe and plough. Monasticism and economic interest in early medieval Sri Lanka. Association for Asian Studies, Monographs and Papers No. XXXV, University of Arixona Press, Tucson, Arizona, 1979; 377 pages, including bibliography and index. - Els Postel-Coster, Jan van Bremen, Romantropologie - Essays over antropologie en literatuur, Antropologisch-Sociologisch Centrum Universiteit van Amsterdam, 1979., Sjaak van der Geest, Jojada Verrips (eds. - Arie de Ruijter, T. Lemaire, Over de waarde van kulturen. Een inleiding in de kultuurfilosofie. Ambo, Baarn 1976, herdruk 1980. 509 blz. - P. van de Velde, W. Arens, The man-eating myth. Oxford University Press, New York, 1979. XIV + 206 pp., 12 illustrations. - E.Ch.L. van der Vliet, Klaus E. Müller, Geschichte der antiken ethnographie und ethnologischen theoriebildung von den anfängen bis auf die byzantinischen historiographen, Teil II (Studien zur Kulturkunde 52, Wiesbaden: Franza Steiner Verlag, 1980. 563 pp. 11 figs. - J.J. de Wolf, P.T.W. Baxter, Age
Full Text Available Cashmere goat skin contains two types of hair follicles (HF: primary hair follicles (PHF and secondary hair follicles (SHF. Although multiple genetic determinants associated with HF formation have been identified, the molecules that determine the independent morphogenesis of HF in cashmere goats remain elusive. The growth and development of SHF directly influence the quantity and quality of cashmere production. Here, we report the transcriptome profiling analysis of nine skin samples from cashmere goats using 60- and 120-day-old embryos (E60 and E120, respectively, as well as newborns (NB, through RNA-sequencing (RNA-seq. HF morphological changes indicated that PHF were initiated at E60, with maturation from E120, while differentiation of SHF was identified at E120 until formation of cashmere occurred after birth (NB. The RNA-sequencing analysis generated over 20.6 million clean reads from each mRNA library. The number of differentially expressed genes (DEGs in E60 vs. E120, E120 vs. NB, and E60 vs. NB were 1,024, 0 and 1,801, respectively, indicating that no significant differences were found at transcriptomic levels between E120 and NB. Key genes including B4GALT4, TNC, a-integrin, and FGFR1, were up-regulated and expressed in HF initiation from E60 to E120, while regulatory genes such as GPRC5D, PAD3, HOXC13, PRR9, VSIG8, LRRC15, LHX2, MSX-2, and FOXN1 were up-regulated and expressed in HF keratinisation and hair shaft differentiation from E120 and NB to E60. Several genes belonging to the KRT and KRTAP gene families were detected throughout the three HF developmental stages. The transcriptional trajectory analyses of all DEGs indicated that immune privilege, glycosaminoglycan biosynthesis, extracellular matrix receptor interaction, and growth factor receptors all played dominant roles in the epithelial-mesenchymal interface and HF formation. We found that the Wnt, transforming growth factor-beta/bone morphogenetic protein, and Notch family
Gao, Ye; Wang, Xiaolong; Yan, Hailong; Zeng, Jie; Ma, Sen; Niu, Yiyuan; Zhou, Guangxian; Jiang, Yu; Chen, Yulin
Cashmere goat skin contains two types of hair follicles (HF): primary hair follicles (PHF) and secondary hair follicles (SHF). Although multiple genetic determinants associated with HF formation have been identified, the molecules that determine the independent morphogenesis of HF in cashmere goats remain elusive. The growth and development of SHF directly influence the quantity and quality of cashmere production. Here, we report the transcriptome profiling analysis of nine skin samples from cashmere goats using 60- and 120-day-old embryos (E60 and E120, respectively), as well as newborns (NB), through RNA-sequencing (RNA-seq). HF morphological changes indicated that PHF were initiated at E60, with maturation from E120, while differentiation of SHF was identified at E120 until formation of cashmere occurred after birth (NB). The RNA-sequencing analysis generated over 20.6 million clean reads from each mRNA library. The number of differentially expressed genes (DEGs) in E60 vs. E120, E120 vs. NB, and E60 vs. NB were 1,024, 0 and 1,801, respectively, indicating that no significant differences were found at transcriptomic levels between E120 and NB. Key genes including B4GALT4, TNC, a-integrin, and FGFR1, were up-regulated and expressed in HF initiation from E60 to E120, while regulatory genes such as GPRC5D, PAD3, HOXC13, PRR9, VSIG8, LRRC15, LHX2, MSX-2, and FOXN1 were up-regulated and expressed in HF keratinisation and hair shaft differentiation from E120 and NB to E60. Several genes belonging to the KRT and KRTAP gene families were detected throughout the three HF developmental stages. The transcriptional trajectory analyses of all DEGs indicated that immune privilege, glycosaminoglycan biosynthesis, extracellular matrix receptor interaction, and growth factor receptors all played dominant roles in the epithelial-mesenchymal interface and HF formation. We found that the Wnt, transforming growth factor-beta/bone morphogenetic protein, and Notch family members
Gòdia, Marta; Mayer, Fabiana Quoos; Nafissi, Julieta; Castelló, Anna; Rodríguez-Gil, Joan Enric; Sánchez, Armand; Clop, Alex
The study of the boar sperm transcriptome by RNA-seq can provide relevant information on sperm quality and fertility and might contribute to animal breeding strategies. However, the analysis of the spermatozoa RNA is challenging as these cells harbor very low amounts of highly fragmented RNA, and the ejaculates also contain other cell types with larger amounts of non-fragmented RNA. Here, we describe a strategy for a successful boar sperm purification, RNA extraction and RNA-seq library preparation. Using these approaches our objectives were: (i) to evaluate the sperm recovery rate (SRR) after boar spermatozoa purification by density centrifugation using the non-porcine-specific commercial reagent BoviPure TM ; (ii) to assess the correlation between SRR and sperm quality characteristics; (iii) to evaluate the relationship between sperm cell RNA load and sperm quality traits and (iv) to compare different library preparation kits for both total RNA-seq (SMARTer Universal Low Input RNA and TruSeq RNA Library Prep kit) and small RNA-seq (NEBNext Small RNA and TailorMix miRNA Sample Prep v2) for high-throughput sequencing. Our results show that pig SRR (~22%) is lower than in other mammalian species and that it is not significantly dependent of the sperm quality parameters analyzed in our study. Moreover, no relationship between the RNA yield per sperm cell and sperm phenotypes was found. We compared a RNA-seq library preparation kit optimized for low amounts of fragmented RNA with a standard kit designed for high amount and quality of input RNA and found that for sperm, a protocol designed to work on low-quality RNA is essential. We also compared two small RNA-seq kits and did not find substantial differences in their performance. We propose the methodological workflow described for the RNA-seq screening of the boar spermatozoa transcriptome. FPKM: fragments per kilobase of transcript per million mapped reads; KRT1: keratin 1; miRNA: micro-RNA; miscRNA: miscellaneous
Silberg, Jonathan J; Tapley, Tim L; Hoff, Kevin G; Vickery, Larry E
The ATPase activity of HscA, a specialized hsp70 molecular chaperone from Escherichia coli, is regulated by the iron-sulfur cluster assembly protein IscU and the J-type co-chaperone HscB. IscU behaves as a substrate for HscA, and HscB enhances the binding of IscU to HscA. To better understand the mechanism by which HscB and IscU regulate HscA, we examined binding of HscB to the different conformational states of HscA and the effects of HscB and IscU on the kinetics of the individual steps of the HscA ATPase reaction cycle. Affinity sensor studies revealed that whereas IscU binds both ADP (R-state) and ATP (T-state) HscA complexes, HscB interacts only with an ATP-bound state. Studies of ATPase activity under single-turnover and rapid mixing conditions showed that both IscU and HscB interact with the low peptide affinity T-state of HscA (HscA++.ATP) and that both modestly accelerate (3-10-fold) the rate-determining steps in the HscA reaction cycle, k(hyd) and k(T-->R). When present together, IscU and HscB synergistically stimulate both k(hyd) (approximately = 500-fold) and k(T-->R) (approximately = 60-fold), leading to enhanced formation of the HscA.ADP-IscU complex (substrate capture). Following ADP/ATP exchange, IscU also stimulates k(R-->T) (approximately = 50-fold) and thereby accelerates the rate at which the low peptide affinity HscA++.ATP T-state is regenerated. Because HscA nucleotide exchange is fast, the overall rate of the chaperone cycle in vivo will be determined by the availability of the IscU-HscB substrate-co-chaperone complex.
Full Text Available BACKGROUND: Zebrafish skin is composed of enveloping and basal layers which form a first-line defense system against pathogens. Zebrafish epidermis contains ionocytes and mucous cells that aid secretion of acid/ions or mucous through skin. Previous studies demonstrated that fish skin is extremely sensitive to external stimuli. However, little is known about the molecular mechanisms that modulate skin cell apoptosis in zebrafish. METHODOLOGY/PRINCIPAL FINDINGS: This study aimed to create a platform to conduct conditional skin ablation and determine if it is possible to attenuate apoptotic stimuli by overexpressing potential apoptosis modulating genes in the skin of live animals. A transgenic zebrafish line of Tg(krt4:NTR-hKikGR(cy17 (killer line, which can conditionally trigger apoptosis in superficial skin cells, was first established. When the killer line was incubated with the prodrug metrodinazole, the superficial skin displayed extensive apoptosis as judged by detection of massive TUNEL- and active caspase 3-positive signals. Great reductions in NTR-hKikGR(+ fluorescent signals accompanied epidermal cell apoptosis. This indicated that NTR-hKikGR(+ signal fluorescence can be utilized to evaluate apoptotic events in vivo. After removal of metrodinazole, the skin integrity progressively recovered and NTR-hKikGR(+ fluorescent signals gradually restored. In contrast, either crossing the killer line with testing lines or transiently injecting the killer line with testing vectors that expressed human constitutive active Akt1, mouse constitutive active Stat3, or HPV16 E6 element displayed apoptosis-resistant phenotypes to cytotoxic metrodinazole as judged by the loss of reduction in NTR-hKikGR(+ fluorescent signaling. CONCLUSION/SIGNIFICANCE: The killer/testing line binary system established in the current study demonstrates a nitroreductase/metrodinazole system that can be utilized to conditionally perform skin ablation in a real-time manner, and
Full Text Available - Christoph von Fürer-Haimendorf, Matthias Hermanns, Die religiös-magische weltanschauung der Primitivstämme Indiens. Band I. Die Bhagoria Bhil. Franz Steiner Verlag. Wiesbaden 1964. 543 seiten, 10 Abb., 2 Karten, 26 tafeln. - S.J. Tambiah, S. Arasaratnam, Ceylon. The Modern Nations in Historical Perspective, Robin W. Winks (General Editor Prentice-Hall, Inc. New Jersey 1964. 172 pages. - Mohan K. Gautam, L.P. Vidyarthi, The Maler. A study in nature-man-spirit complex of a hill tribe in Bihar. Foreword by Julian Steward. XVI and 261 pp., with 24 plates, 6 tables, 12 figures, 15 appendices with a glossary of local terms. Calcutta 1963. Bookland Private Ltd. - L. Sluimers, J.M. Halpern, Government, politics and social structure in Laos: A study of tradition and innovation. Wyoming enz., The Cellar Bookshop, 1964. VIII, 197 blz. Southeast Asia Studies, Yale University; Monograph Series No. 4. - P.E. de Josselin de Jong, M.G. Swift, Malay peasant society in Jelebu. L.S.E. Monographs on Social Anthropology no. 29. The Athlone Press, London 1965. 178 pp. - C.H.M. Nooy-Palm, John M. Garvan, The Negritos of the Philippines. Edited by Hermann Hochegger. Wiener Beiträge zur Kulturgeschichte und Linguistik, Band XIV. Verlag Ferdinand Berger, Horn-Wien 1963. 288 pgs., krt. - L.F.B. Dubbeldam, H.L. Peters, Enkele Hoofdstukken uit het sociaal-religieuze leven van een Dani-groep. Diss. 1965 Utrecht, printed by Dagblad voor Noord-Limburg N.V. Venlo. 184 pp., ills. - R. Roolvink, Hans Andreas Poetzelberger, Einführung in das Indonesische. Wiesbaden, 1965. 147 pages, 1 table, 1 map. - P. Voorhoeve, M.D. Wainwright, A guide to western manuscripts and documents in the British Isles relating to South and South East Asia. Compiled by M.D. Wainwright and N. Matthews under the general supervision of J.D. Pearson. London 1965. xix, 352 pp., N. Matthews (eds.
Full Text Available Barrett's esophagus (BE is an intestinal metaplasia that occurs in the setting of chronic acid and bile reflux and is associated with a risk for adenocarcinoma. Expression of intestine-specific transcription factors in the esophagus likely contributes to metaplasia development. Our objective was to explore the effects of an intestine-specific transcription factor when expressed in the mouse esophageal epithelium. Transgenic mice were derived in which the transcription factor Cdx2 is expressed in squamous epithelium using the murine Keratin-14 gene promoter. Effects of the transgene upon cell proliferation and differentiation, gene expression, and barrier integrity were explored. K14-Cdx2 mice express the Cdx2 transgene in esophageal squamous tissues. Cdx2 expression was associated with reduced basal epithelial cell proliferation and altered cell morphology. Ultrastructurally two changes were noted. Cdx2 expression was associated with dilated space between the basal cells and diminished cell-cell adhesion caused by reduced Desmocollin-3 mRNA and protein expression. This compromised epithelial barrier function, as the measured trans-epithelial electrical resistance (TEER of the K14-Cdx2 epithelium was significantly reduced compared to controls (1189 Ohm*cm(2 ±343.5 to 508 Ohm*cm(2±92.48, p = 0.0532. Secondly, basal cells with features of a transitional cell type, intermediate between keratinocytes and columnar Barrett's epithelial cells, were observed. These cells had reduced keratin bundles and increased endoplasmic reticulum levels, suggesting the adoption of secretory-cell features. Moreover, at the ultrastructural level they resembled "Distinctive" cells associated with multilayered epithelium. Treatment of the K14-Cdx2 mice with 5'-Azacytidine elicited expression of BE-associated genes including Cdx1, Krt18, and Slc26a3/Dra, suggesting the phenotype could be advanced under certain conditions. We conclude that ectopic Cdx2 expression in
Kováč, Viliam; Gavurová, Beáta
Poverty and social exclusion is measured through different criteria and one of them is the health sector. The relationship between Roma population and the health sector is on the edge of researchers' interest in the Slovak Republic. The purpose of this paper is a quantification of the regional disparities in the development of mortality which is causally linked with selected infrastructural determinants - namely access to water and sewerage. These determinants differently participate in the structure of mortality in marginalised and segregated communities and they deepen regional disparities in health. It is a spatial analysis of the districts of the Slovak Republic. The data from the Atlas of Roma communities in Slovakia 2013 is applied. Through the multiple linear regression model the relationship between mortality of the Roma population and water and sewerage availability in the Roma settlements is examined. Similarity between the districts is measured by the Euclidean metric system. The most appropriate district for representing the Slovak Republic average is the Dunajská Streda district in a field of arithmetic mean and the Veľký Krtíš district in a field of median value. The outermost district is represented by the Košice-okolie district, conversely, the Trnava district is the closest to the rest of the Slovak Republic. The highest statistically significant impacts on mortality are explored in public water supply extension plan and public sewerage supply extension plan. It seems that water play a greater role in determining health of Roma population. The highest number of inhabitants with supplied public water and public sewerage is kept by the Kežmarok district, the Košice district, and the Spišská Nová Ves district. Our results can be beneficial for health decision making, since in the Strategic Framework for Health of the Slovak Republic metrics for measuring and evaluating health aspects in Roma communities absent and that prevents them to be
Hayashi, Ken-Go; Hosoe, Misa; Kizaki, Keiichiro; Fujii, Shiori; Kanahara, Hiroko; Takahashi, Toru; Sakumoto, Ryosuke
Repeat breeding directly affects reproductive efficiency in cattle due to an increase in services per conception and calving interval. This study aimed to investigate whether changes in endometrial gene expression profile are involved in repeat breeding in cows. Differential gene expression profiles of the endometrium were investigated during the mid-luteal phase of the estrous cycle between repeat breeder (RB) and non-RB cows using microarray analysis. The caruncular (CAR) and intercaruncular (ICAR) endometrium of both ipsilateral and contralateral uterine horns to the corpus luteum were collected from RB (inseminated at least three times but not pregnant) and non-RB cows on Day 15 of the estrous cycle (4 cows/group). Global gene expression profiles of these endometrial samples were analyzed with a 15 K custom-made oligo-microarray for cattle. Immunohistochemistry was performed to investigate the cellular localization of proteins of three identified transcripts in the endometrium. Microarray analysis revealed that 405 and 397 genes were differentially expressed in the CAR and ICAR of the ipsilateral uterine horn of RB, respectively when compared with non-RB cows. In the contralateral uterine horn, 443 and 257 differentially expressed genes were identified in the CAR and ICAR of RB, respectively when compared with non-RB cows. Gene ontology analysis revealed that genes involved in development and morphogenesis were mainly up-regulated in the CAR of RB cows. In the ICAR of both the ipsilateral and contralateral uterine horns, genes related to the metabolic process were predominantly enriched in the RB cows when compared with non-RB cows. In the analysis of the whole uterus (combining the data above four endometrial compartments), RB cows showed up-regulation of 37 genes including PRSS2, GSTA3 and PIPOX and down-regulation of 39 genes including CHGA, KRT35 and THBS4 when compared with non-RB cows. Immunohistochemistry revealed that CHGA, GSTA3 and PRSS2 proteins
Gillbro, J M; Al-Bader, T; Westman, M; Olsson, M J; Mavon, A
Synopsis Objective Retinoids are used as therapeutic agents for numerous skin diseases, for example, psoriasis, acne and keratinization disorders. The same substances have also been recognized in the treatment for hyperpigmentation disorders such as melasma. Other studies on photo-damaged skin have shown that retinoids reduce wrinkles, surface roughness, mottled pigmentation, and visual skin appearance as a whole. We tested the hypothesis that an organoculture of full-thickness human skin could be used as a preclinical model to investigate the retinoid transcriptional profile in human skin in vitro. Methods Full-thickness skin explants were exposed to topically applied all-trans retinoic acid (RA) for 24 h. The gene expression profile was analysed using oligonucleotide microarrays, and data were validated with real-time (RT) PCR. Results We showed that the expression of 93 genes was significantly altered more than twofold. Several of the altered genes, for example, KRT4, CYP26 and LCN2, have previously been shown to be affected by RA in keratinocyte monocultures, reconstructed epidermis and skin biopsies from patients treated topically or orally with RA. In addition, genes, such as SCEL, NRIP1, DGAT2, RDH12 EfnB2, MAPK14, SAMD9 and CEACAM6 not previously reported to be affected by RA in human skin, were identified for the first time in this study. Conclusion The results in the present study show that full-thickness human explants represent a valuable pre-clinical model for studying the effects of retinoids in skin. Résumé Objectif Les rétinoïdes sont utilisés comme agents thérapeutiques pour de nombreuses maladies de la peau, p.ex. le psoriasis, l'acné et les troubles de la kératinisation. Les mêmes substances ont également été reconnues dans le traitement des troubles de l' hyperpigmentation tels que le melasma. D'autres études sur la peau photo-endommagée ont montré que les rétinoïdes réduisent les rides, la rugosité de la surface, la
Full Text Available - D. van der Horst, Albert Herrmann, An historical atlas of China. New edition by Norton Ginsburg. Djambatan N.V., Amsterdam 1966. 88 pp. - A.F.P. Hulsewé, F.S. Drake, Symposium of historical, archaeological and linguistic studies on Southern China, South-East Asia and the Hongkong region. Proceedings of a meeting held in September 1961 as part of the Golden Jubilee Congress of the University of Hongkong. Hongkong, Hongkong University Press, 1967. X + 370 pp. - D.R. Jonker, Liu Shih-Shun, One hundred and one Chinese poems. With English translations and preface. UNESCO Collection of Representative Works, Chinese Series; Hong Kong University Press, 1967. XXXIX + 173 pp. - M.A.P. Meilink-Roelofsz, A. Das Gupta, Malabar in Asian trade 1740-1800. Cambridge South Asian Studies. Cambridge U.P. 1967. XII, 204 blz. Met krt. - C.R. Hooijer, Per Sorensen, Ban-Kao, Neolithic settlements with cemeteries in the Kanchanaburi Province. 140 pp., 140 plates, 4 maps, figs. The Thai-Danish Prehistoric Expedition 1960-62, Archaeological Excavations in Thailand, Vol. II. Munksgaard, Copenhagen, 1967. - C.R. Hooijer, H.R. van Heekeren, Sai-Yok, Stone-age settlements in the Kanchanaburi Province. 129 pp., 33 plates, 47 figs. The Thai-Danish Prehistoric Expedition 1960-1962, Archaeological Excavations in Thailand, Vol. I. Munksgaard, Copenhagen, 1967., Eigil Knuth (eds. - Th. G. Th. Pigeaud, C. Hooykaas, Bagus Umbara, Prince of Koripan. The story of a prince of Bali and a princess of Java, illustrated on palm leaves by a Balines artist. With Balinese text and English translation by Dr C. Hooykaas, Reader in Old Javanese, University of London. Published by the Trustees of the British Museum, London, 1968. 55 pp., 9 illustrations, 31 x 25 cm. - H.J. de Graaf, Soemarsaid Moertono, State and statecraft in old Java: A study of the late Mataram period 16th to 19th century. Monograph series Modern Indonesia Project. Southeast Asia Program Department of Asian Studies. Cornell
Full Text Available - A.J.C. Lach de Bére, Fernand van Langenhove, Consciences Tribales et Nationales en Afrique Noire. Institut Royal des Relations Internationales, Bruxelles. Martinus Nijhoff, ‘s-Gravenhage, 1960; 444 blz. - J.H. Scherer, A.H.J. Prins, The Swahili-speaking peoples of Zanzibar and the E. African Coast (Arabs, Shirazi and Swahili. Ethnographic Survey of Africa: East Central Africa, part XII. Uitgave van het International African Institute, London, 1961. 143 pp., m. kaart. - P. Driessens, Carol Brubaker, Geesten van het woud. Servire Luxe Pockets nr. 66. Servire, Den Haag 1963. 175 pp., 24 foto’s. - Joh. J. Hanrath, Indonesian Economics. The concept of dualism in theory and policy. Den Haag (W. van Hoeve 1961. 443 pp. - W. Ph. Coolhaas, H.R.C. Wright, East-Indian economic problems of the age of Cornwallis and Raffles. Luzac, London, 1961; 271 pp. - H.J. de Graaf, M.A.P. Meilink-Roelofsz, Asian trade and European influence in the Indonesian Archipelago between 1500 and about 1630. Academisch Proefschrift Amsterdam (S.U.. M. Nijhoff, ‘s-Gravenhage 1962. 471 pp. - Logemann, Herbert Feith, The decline of constitutional democracy in Indonesia. Cornell University Press, Ithaca, New York, 1962. XX en 608 blz. - F.D.K. Bosch, G. Coedés, Les peuples de la péninsule indochinoise. 228 pp., 16 pl., 1 carte; Ed. Dunod, Paris, 1962. - L. Sluimers, Sirdar Ikbal Ali Shah, Viet-nam. London, Octagon Press, 1960. XV, 232 blz., krt. - L. Sluimers, J.G. Keyes, A bibliography of North Vietnamese Publications in the Cornell University Library. Ithaca, Cornell University, 1962. Data paper: Number 47. Southeast Asia Program. Department of Asian Studies. Cornell University. X, 116 blz., X. - A.F.P. Hulsewé, G.P. Oery, The Man-Shu (Book of the Southern Barbarians, translated by Gordon H. Luce, edited by G.P. Oery; Data Paper Nr. 44, Southeast Asia Program, Dept. of Far Eastern Studies, Cornell Univ., Ithaca, N.Y.; 1961. (X + 116 pp., 1 map. - C.H.M. Palm, Felix M
J. van Baal
fig. - S. Kooijman, P.K. Neuhaus, Beiträge zur Ethnographie der Pala, Mittel Neu Irland (aus dem Nachlass bearbeitet von P.C. Laufer, MSC und Carl A. Schmitz. Kölner Ethnologische Mitteilungen, Köln 1962. 452 S., 28 Abb. - J. van Baal, Peter Matthiessen, De Zonen van Nopoe; Een Kroniek uit het Steentijdperk. Vertaald uit het Engels door Beb Vuyk. J.A. Boom en Zoon, Meppel. - J. Prins, Robert R. Jay, Religion and politics in rural central Java. Cultural Report Series no. 12, Southeast Asia Studies - Yale University. VIII en 107 pagina’s, en een bibliografie. - L. Sluimers, G.I. Lewinson, Philippiny mezjdu perwoj i wtoroj mirowymi wojnami. Moskwa, Izdateljstwo wostotsjnoj literatury, 1958. (G.I. Lewinson, De Philippijnen tussen de Eerste en de tweede Wereldoorlog. Moskou, Uitgeverij voor Oosterse Literatuur, 1958. 288 blz., krt. - R.T. Zuidema, Rafael Girard, Los Mayas Eternos XIV, 493 blz., 250 foto’s en vele tekeningen, schema en 5 kaarten. Antigua Librería Robredo, Mexico D.F. 1962. - R.T. Zuidema, Bodo Spranz, Göttergestalten in den Mexikanischen Bilderhandschriften der Codex Borgia-Gruppe. Eine ikonographische Untersuchung. Acta Humboldtiana, Series Geographica et Ethnographica Nr. 4. Franz Steiner Verlag GmbH. Wiesbaden, 1964. 435 blz., 1791 fig., 32 afb., 2 tabellen.
Horton, W.; Goniche, M.; Peysson, Y.; Decker, J.; Ekedahl, A.; Litaudon, X.
Full text of publication follows. The propagation and scattering of the 5 GHz RF waves planned for driving and controlling the plasma current in stage 2 of ITER is analyzed with theory, simulations and data from Tore Supra. The internal RF wavenumber spectrum is determined by a combination of elements including the (1) the azimuthal spectrum launched by the antenna, (2) coupling of the radial and azimuthal oscillations of the ray trajectories described the ray Hamiltonian with the radial and the poloidal variation of plasma and scattering from the drift wave turbulence (ref. 1, 2). The scattering of the RF waves from the drift wave turbulence in the plasma is described through a Fokker-Planck equation for the probability density of the rays. The new 4D ray kinetic equation has (1) an edge source from the antenna, (2) a core sink from the electron resonances, and (3) a global scattering rate tensor D ij (k,r,t) derived from the ambient plasma turbulence. The tensor reduces to a parallel and cross-field component with the cross-field component describing side-scatter of the RF waves. The solutions give a spectral distribution for the parallel index of refraction from the antenna to the region of three times the core electron thermal velocity. Strong absorption of the rays occurs where the plateau in the fast electron distribution joins the steeply increasing slope of the thermal electron phase space density (ref. 3). Solutions of the ray kinetic equation with the source, sink and scattering provide the filling of the spectral gap and the efficiency of the LHCD system. The ETG turbulence is modified by the temperature anisotropies and the sharp radial gradients of the LHCD electron distribution function (ref. 3). In the presence of the ETG turbulence projections of the partial differential equations to low-order transport models are derived with dynamical feed-forward/ feedback loops following L-H-ELM modeling (ref. 4). The low-order models may be used with feedback
Ajdari, Armand; Stone, Howard A.
, simulation and theory, in this rapidly developing field. Focus on Micro- and Nanofluidics Contents The anti-lotus leaf effect in nanohydrodynamic bump arrays Keith Morton, Ophelia K C Tsui, Chih-Kuan Tung, James C Sturm, Stephen Y Chou and Robert Austin Transport in nanofluidic systems: a review of theory and applications W Sparreboom, A van den Berg and J C T Eijkel The effects of polymer molecular weight on filament thinning and drop breakup in microchannels P E Arratia, L-A Cramer, J P Gollub and D J Durian Mass transfer and interfacial properties in two-phase microchannel flows Jeffrey D Martin and Steven D Hudson Temporal response of an initially deflected PDMS channel Priyadarshi Panda, Kai P Yuet, Dhananjay Dendukuri, T Alan Hatton and Patrick S Doyle Gas-liquid two-phase flow patterns in rectangular polymeric microchannels: effect of surface wetting properties D Huh, C-H Kuo, J B Grotberg and S Takayama Mixing via thermocapillary generation of flow patterns inside a microfluidic drop María Luisa Cordero, Hans Olav Rolfsnes, Daniel R Burnham, Paul A Campbell, David McGloin and Charles N Baroud Pressure-driven DNA transport across an artificial nanotopography J T Del Bonis-O'Donnell, W Reisner and D Stein Eulerian indicators for predicting and optimizing mixing quality Rob Sturman and Stephen Wiggins Asymmetric flows over symmetric surfaces: capacitive coupling in induced-charge electro-osmosis T S Mansuripur, A J Pascall and T M Squires High-viscosity fluid threads in weakly diffusive microfluidic systems T Cubaud and T G Mason Interfacial mass transport in steady three-dimensional flows in microchannels Joseph D Kirtland, Corey R Siegel and Abraham D Stroock Active connectors for microfluidic drops on demand Jean-Christophe Galas, Denis Bartolo and Vincent Studer Electrokinetic control of sample splitting at a channel bifurcation using isotachophoresis Alexandre Persat and Juan G Santiago Differential inertial focusing of particles in curved low