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  • 1
    Publication Date: 2018-08-02
    Description: Jinwoo Seong, Nam-Shik Kim, Jee-Ah Kim, Wonbin Lee, Ji-Yun Seo, Min Kyu Yum, Ji-Hoon Kim, Inkuk Park, Jong-Seol Kang, Sung-Hwan Bae, Cheol-Heui Yun, and Young-Yun Kong Mammary glands develop through primary ductal elongation and side branching to maximize the spatial area. Although primary ducts are generated by bifurcation of terminal end buds, the mechanism through which side branching occurs is still largely unclear. Here, we show that inhibitor of DNA-binding 2 (ID2) drives side branch formation through the differentiation of K6 + bipotent progenitor cells (BPs) into CD61 + luminal progenitor cells (LPs). Id2 -null mice had side-branching defects, along with developmental blockage of the differentiation of K6 + BPs into CD61 + LPs. Notably, CD61 + LPs were found in budding and side branches, but not in terminal end buds. Hormone reconstitution studies using ovariectomized MMTV-hemagglutinin-nuclear localized sequence-tagged Id2 transgenic mice revealed that ID2 is a key mediator of progesterone, which drives luminal lineage differentiation and side branching. Our results suggest that CD61 is a marker of side branches and that ID2 regulates side branch formation by inducing luminal lineage commitment from K6 + BPs to CD61 + LPs.
    Print ISSN: 0950-1991
    Electronic ISSN: 1477-9129
    Topics: Biology
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  • 2
    Publication Date: 2018-07-18
    Description: Interferon-stimulated gene 15 (ISG15) encodes a ubiquitin-like protein that can be conjugated to proteins via an enzymatic cascade involving the E1, E2, and E3 enzymes. ISG15 expression and protein ISGylation modulate viral infection; however, the viral mechanisms regulating the function of ISG15 and ISGylation are not well understood. We recently showed that ISGylation suppresses the growth of human cytomegalovirus (HCMV) at multiple steps of the virus life cycle and that the virus-encoded pUL26 protein inhibits protein ISGylation. In this study, we demonstrate that the HCMV UL50-encoded transmembrane protein, a component of the nuclear egress complex, also inhibits ISGylation. pUL50 interacted with UBE1L, an E1-activating enzyme for ISGylation, and (to a lesser extent) with ISG15, as did pUL26. However, unlike pUL26, pUL50 caused proteasomal degradation of UBE1L. The UBE1L level induced in human fibroblast cells by interferon beta treatment or virus infection was reduced by pUL50 expression. This activity of pUL50 involved the transmembrane (TM) domain within its C-terminal region, although pUL50 could interact with UBE1L in a manner independent of the TM domain. Consistently, colocalization of pUL50 with UBE1L was observed in cells treated with a proteasome inhibitor. Furthermore, we found that RNF170, an endoplasmic reticulum (ER)-associated ubiquitin E3 ligase, interacted with pUL50 and promoted pUL50-mediated UBE1L degradation via ubiquitination. Our results demonstrate a novel role for the pUL50 transmembrane protein of HCMV in the regulation of protein ISGylation. IMPORTANCE Proteins can be conjugated covalently by ubiquitin or ubiquitin-like proteins, such as SUMO and ISG15. ISG15 is highly induced in viral infection, and ISG15 conjugation, termed ISGylation, plays important regulatory roles in viral growth. Although ISGylation has been shown to negatively affect many viruses, including human cytomegalovirus (HCMV), viral countermeasures that might modulate ISGylation are not well understood. In the present study, we show that the transmembrane protein encoded by HCMV UL50 inhibits ISGylation by causing proteasomal degradation of UBE1L, an E1-activating enzyme for ISGylation. This pUL50 activity requires membrane targeting. In support of this finding, RNF170, an ER-associated ubiquitin E3 ligase, interacts with pUL50 and promotes UL50-mediated UBE1L ubiquitination and degradation. Our results provide the first evidence, to our knowledge, that viruses can regulate ISGylation by directly targeting the ISGylation E1 enzyme.
    Print ISSN: 0022-538X
    Electronic ISSN: 1098-5514
    Topics: Medicine
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  • 3
    Publication Date: 2014-04-12
    Description: Genome-wide characterization of the in vivo cellular response to perturbation is fundamental to understanding how cells survive stress. Identifying the proteins and pathways perturbed by small molecules affects biology and medicine by revealing the mechanisms of drug action. We used a yeast chemogenomics platform that quantifies the requirement for each gene for resistance to a compound in vivo to profile 3250 small molecules in a systematic and unbiased manner. We identified 317 compounds that specifically perturb the function of 121 genes and characterized the mechanism of specific compounds. Global analysis revealed that the cellular response to small molecules is limited and described by a network of 45 major chemogenomic signatures. Our results provide a resource for the discovery of functional interactions among genes, chemicals, and biological processes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4254748/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4254748/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Anna Y -- St Onge, Robert P -- Proctor, Michael J -- Wallace, Iain M -- Nile, Aaron H -- Spagnuolo, Paul A -- Jitkova, Yulia -- Gronda, Marcela -- Wu, Yan -- Kim, Moshe K -- Cheung-Ong, Kahlin -- Torres, Nikko P -- Spear, Eric D -- Han, Mitchell K L -- Schlecht, Ulrich -- Suresh, Sundari -- Duby, Geoffrey -- Heisler, Lawrence E -- Surendra, Anuradha -- Fung, Eula -- Urbanus, Malene L -- Gebbia, Marinella -- Lissina, Elena -- Miranda, Molly -- Chiang, Jennifer H -- Aparicio, Ana Maria -- Zeghouf, Mahel -- Davis, Ronald W -- Cherfils, Jacqueline -- Boutry, Marc -- Kaiser, Chris A -- Cummins, Carolyn L -- Trimble, William S -- Brown, Grant W -- Schimmer, Aaron D -- Bankaitis, Vytas A -- Nislow, Corey -- Bader, Gary D -- Giaever, Guri -- GM103504/GM/NIGMS NIH HHS/ -- GM44530/GM/NIGMS NIH HHS/ -- MOP-700724/Canadian Institutes of Health Research/Canada -- MOP-79368/Canadian Institutes of Health Research/Canada -- MOP-81340/Canadian Institutes of Health Research/Canada -- P01 HG000205/HG/NHGRI NIH HHS/ -- P41 GM103504/GM/NIGMS NIH HHS/ -- R01 003317-07/PHS HHS/ -- R01 CA157456/CA/NCI NIH HHS/ -- R01 GM044530/GM/NIGMS NIH HHS/ -- R01 HG003317/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2014 Apr 11;344(6180):208-11. doi: 10.1126/science.1250217.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24723613" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line, Tumor ; Cells/*drug effects ; Drug Evaluation, Preclinical/*methods ; Drug Resistance/*genetics ; *Gene Regulatory Networks ; Genome-Wide Association Study/*methods ; Haploinsufficiency ; Humans ; Pharmacogenetics ; Saccharomyces cerevisiae/drug effects/genetics ; Small Molecule Libraries/*pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2018-04-20
    Description: Objective There is some evidence that lung function and chronic kidney disease (CKD) may be related. We evaluated the impact of lung function on the development of CKD in a large-scale longitudinal study. Method Retrospective longitudinal analyses were conducted among subjects who participated in comprehensive health check-ups at least four times during 7 years (between 2006 and 2012). We investigated the development of CKD during the follow-up period according to lung function status. Results Ten thousand one hundred and twenty-eight individuals (mean age =51.2 years) without CKD at baseline were enrolled. During the mean follow-up of 5 years (58.5±14.4 months), 167 of the 10 128 subjects (1.6%) developed CKD. Multivariable Cox proportional hazards analyses adjusting for age, sex, body mass index, systolic blood pressure, fasting glucose, estimated glomerular filtration rate, uric acid, triglycerides, serum albumin, and the presence of diabetes and hypertension revealed that a decrease of 10% in the forced expiratory volume in 1s (FEV 1 )/forced vital capacity (FVC) ratio was associated with a 35% increase in the development of CKD during the follow-up. The incidence of CKD was higher in those with an FEV 1 /FVC ratio 〈0.8 compared with those with FEV 1 /FVC ratio ≥0.8 (HR=1.454; 95% CI 1.042 to 2.028, p=0.028). Conclusions Limited airflow as measured by the FEV 1 /FVC ratio was associated with an increased risk of CKD.
    Keywords: Open access, Renal medicine
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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  • 5
    ISSN: 1365-2842
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The placement of dental implants in the molar region of the maxilla is often difficult because of insufficient bone volume and the inferior bone quality. In order to avoid these limitations, the pillar of bone, which is composed of the maxillary tuberosity, the pyramidal process of the palatine bone and the pterygoid process of the sphenoid bone, was introduced for implant placement. In fact, the pyramidal process is the posterior structure where implants are placed but until now, there is no available data of the size or shape of the pyramidal process. Therefore, we measured the height, anteroposterior distance and mediolateral distance of the pyramidal process and observed the shape of lateral and posterior surfaces of the pyramidal process of 54 Korean edentulous dry skulls in this study. The height was 13·1 mm (male: 13·6 mm, female: 12·4 mm). The anteroposterior distance was 6·5 mm (male: 6·7 mm, female: 6·1 mm). The mediolateral distance was 9·5 mm (male: 9·9 mm, female: 9·0 mm). The most common type was the right-angled triangle in the lateral surface (44·4%) and in the posterior surface (66·7%). There was no statistical significance between the male and the female in all items (P 〉 0·05). These results provide anatomical features in relation to placement of dental implants in the molar region of the maxilla and would be useful in treatment planning of partially or completely edentulous patients.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  A keloid results from excessive collagen deposition, the cause of which remains elusive. A thorough understanding of the pathophysiology of keloid tissue can help determine the most appropriate treatment strategy.Objectives  To assess the differences in gene expression between keloids and adjacent normal skin in order to define the genes involved in keloid formation.Methods  Three Korean patients with keloids underwent excision of the keloid and adjacent normal skin, which was used as the control. We investigated expression patterns of genes in the keloids and the normal skin using cDNA microarray and in situ hybridization techniques.Results  Nine genes in the keloid tissue were consistently upregulated over the 2·0 ratio compared with the normal control from the cDNA microarray composed of 3063 clones: collagen type I α1 (〈accessionId ref="info:ddbj-embl-genbank/NM_000088"〉NM_000088), DNA segment on chromosome 21 (unique) 2056 expressed sequence (D21S2056E, NNP-1, 〈accessionId ref="info:ddbj-embl-genbank/NM_003683"〉NM_003683), suppressor of Ty 5 homologue (〈accessionId ref="info:ddbj-embl-genbank/NM_003169"〉NM_003169), phosphoglycerate dehydrogenase (〈accessionId ref="info:ddbj-embl-genbank/NM_032692"〉NM_032692), adenosine triphosphate synthase β (〈accessionId ref="info:ddbj-embl-genbank/NM_001686"〉NM_001686), serine (or cysteine) proteinase inhibitor, clade H (heat shock protein 47, 〈accessionId ref="info:ddbj-embl-genbank/NM_001235"〉NM_001235), LIV-1 protein, oestrogen regulated (LIV-1, 〈accessionId ref="info:ddbj-embl-genbank/NM_012319"〉NM_012319), interleukin-11 receptor α (IL11RA, 〈accessionId ref="info:ddbj-embl-genbank/NM_004512"〉NM_004512) and carbonyl reductase 3 (CBR3, 〈accessionId ref="info:ddbj-embl-genbank/NM_001236"〉NM_001236). From the in situ hybridization study, the staining signals in the keloid tissue hybridized with anti sense probes of NNP-1 mRNA were stronger than signals in normal controls. Further, endothelial epithelium, but not the epidermis, expressed the signal equally in both keloid and normal control tissue.Conclusions  We identified nine upregulated genes in keloid tissue using cDNA microarray. Of the nine, the NNP-1 gene was confirmed by topological information using the in situ hybridization technique. We conclude that these nine genes, especially NNP-1, probably contribute either directly or indirectly to keloid formation.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 0178-515X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract  Production of exopolysaccharide (EPS) from a strain of Bacillus polymyxa was studied. Sucrose and potassium nitrate were found to be efficient carbon and nitrogen sources, respectively, for the production of the EPS. EPS production increased with the increase of sucrose concentration, probably due to the facilitated carbon uptake. Optimal pH was 7–8, and a sufficient supply of oxygen was needed for the EPS production. It was noted that the EPS synthesis by this B. polymyxa was growth-associated, indicating that a sufficient supply of nutrients was required for a high production of the EPS. As high as 54 g/l of EPS with a yield of 63% (g EPS/g sucrose) was obtained in 48 h of fed-batch cultivation with intermittent feeding of sucrose and potassium nitrate.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 0178-515X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Influence of dissolved oxygen level on production of curdlan by Agrobacterium species was investigated. Preliminary shake flask experiments showed that both cell growth and curdlan production were higher at a smaller volume of medium (50–100 ml in 500 ml flasks). As culture volume increased from 100 ml to 300 ml, both cell concentration and curdlan production decreased, indicating that higher oxygen transfer is required for a higher production of curdlan. Time profiles of cell concentration and curdlan production in a 5-liter jar fermentation at different agitation speeds, ranging from 300 rpm to 700 rpm, supported the fact of higher production of curdlan at higher oxygen transfer rate observed in shake flask cultures. At a higher agitation speed (600 rpm), the highest curdlan production (64.4 g/l) was obtained in 120 h of a batch fermentation. However, curdlan production was not improved at the higher agitation speed (700 rpm). For the mass production of curdlan, fermentation was performed in a 300-liter fermenter under the condition where the same volumetric oxygen transfer coefficient was obtained as in 5-liter jar fermentation. As high as 9.28 kg of curdlan with a final concentration of 58 g/l was obtained in 120 h batch cultivation, enlarging the potential in the industrial production of curdlan.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The atomic force microscope (AFM) tip biased at around −15 V is found to be capable of locally modifying the entire thickness of 40-nm-thick semiconducting or superconducting YBa2Cu3O7−y microstrips in air. We show, using combined electrical and AFM measurements, that the local regions underneath the surface of the semiconducting or superconducting YBa2Cu3O7−y microstrips are transformed into either nonconducting or nonsuperconducting regions, respectively, upon applying the negatively biased AFM tip. The conductance of the nonsuperconducting regions is also found to be comparable to that of the superconducting regions before modification at 298 K. © 2000 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Biochemistry 3 (1964), S. 1169-1174 
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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