Journal articles: 'UCOE'

1

Nelson, Everette J. R., Laura M. Tuschong, and Dennis D. Hickstein. "Lentiviral Vectors Incorporating Ubiquitous Chromatin Opening Element Driving Canine CD18 Expression." Blood 128, no. 22 (December 2, 2016): 5890. http://dx.doi.org/10.1182/blood.v128.22.5890.5890.

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Abstract Leukocyte adhesion deficiency type 1 (LAD1) in humans is caused due to mutations in the ITGB2 gene encoding the leukocyte CD18 subunit (b2 integrin). This results in defective leukocyte adhesion and migration leading to recurrent episodes of life-threatening bacterial infection. Canine leukocyte adhesion deficiency (CLAD) represents a disease-specific large animal model of LAD1 in which new therapeutic approaches could be tested. Our previous studies have demonstrated variable efficiency of CD18 expression under the control of several promoters. These include cellular promoters such as those of human elongation factor 1a (hEF1a): long (1169bp) and short (248bp) fragments, human phosphoglycerate kinase (hPGK), human CD11b and human CD18 genes. In addition, murine stem cell virus (MSCV) promoter has also been demonstrated to lead to very high levels of CD18 expression in CLAD CD34+ cells thereby reversing the CLAD phenotype in dogs previously treated with both foamy and lentiviral vectors. But, due to potential genotoxicity associated with the use of viral promoters, we continued our efforts in search of novel cellular promoters. One such promoter is the ubiquitous chromatin opening element (UCOE) from the human heterogeneous ribonucleoprotein A2/B1 and chromobox homolog 3 (HNRPA2B1-CBX3) loci. UCOE has been previously shown to display reproducible and stable transgene expression within the context of a self-inactivating (SIN) lentiviral vector in the absence of classical enhancer activity (Zhang et al., Blood 2007).It has also been shown to confer resistance to DNA methylation-mediated transgene silencing even upon integration into the heterochromatin regions of the host chromosome (Zhang et al., Mol Ther. 2010). Since the full-length element is about 2.6 kb, we cloned and tested different fragment lengths of the UCOE promoter in a SIN lentiviral vector (pCL20) in CLAD CD34+ cells in vitro. Efficiency of expression of CD18 obtained with the six promoter fragments of UCOE (in bp), namely U3'631, U3'1262, U3'652, U5'1357, U5'723 and U5'655 were compared to those obtained with an MSCV promoter. Functional viral titers were first determined using a human LAD EBV-transformed B-cell line that lacks endogenous human CD18. When comparable titers of each vector were used in an overnight transduction of CLAD CD34+ cells after a 24h cytokine prestimulation in vitro, the percentage of CD18+ cells 5 days after transduction were as follows: U3'631 - 8.49%, U3'1262 - 15.9%, U3'652 - 21.3% (tested at MOI 100), U5'1357 - 2.05% (tested at MOI 30), U5'723 - 2.44% (tested at MOI 20), U5'655 - 3.01% (tested at MOI 50) and MSCV - 35.3% (tested at MOI 100). The CD18 expression levels driven by some of these promoter fragments were comparable to those driven by cellular promoters mentioned previously. The UCOE is promising in that it could overcome possible gene silencing effects when used in vivo, unlike promoters such as EF1a and PGK which were largely subjected to post-transcriptional gene silencing with sub-therapeutic levels of CD18 as previously tested in the dog model. Hence, functional correction of the CD18 defect could be achieved with candidate UCOE-incorporating SIN lentiviral vector(s) when used in the treatment of CLAD dogs. Disclosures No relevant conflicts of interest to declare.

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Ikawa, Yasuhiro, Toru Uchiyama, Guridevi Jayashree Jagadeesh, and Fabio Candotti. "Comparison of Immortalization Potential of Gamma-Retroviral, Lentiviral and Foamy Virus Gene Transfer Vectors." Blood 118, no. 21 (November 18, 2011): 3116. http://dx.doi.org/10.1182/blood.v118.21.3116.3116.

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Abstract Abstract 3116 Therapeutic gene transfer has been used successfully to treat a variety of human genetic diseases. Although protocols have shown positive clinical outcomes, the success of clinical trials were tempered by adverse events, in which integration of the viral vectors increased transcription of cancer-related genes and thereby contributed to development of leukemia. In all documented cases of insertional mutagenesis, the viral vectors used contained full-length, gamma-retrovirus long terminal repeats (LTRs) that are able to exert strong promoter and enhancer activity driving not only the expression of the transgene carried by the vector, but also that of genes neighboring the insertion site. Assessing safety of integrating viral vectors for future clinical use is therefore of paramount importance. In preparation for gene therapy approaches for the Wiskott-Aldrich syndrome (WAS), we used an in vitro assay of murine bone marrow (BM) cell immortalization to compare the consequences of transduction by four different kinds of viral vectors, including a full-length LTR Moloney leukemia virus (MLV), a self-inactivating MLV carrying a 3' LTR deleted of the viral enhancer region (SIN), a lentivirus (LV), and a foamy virus (FV) construct. All vectors carried EGFP under the control of a ubiquitously acting chromatin opening element (UCOE) or the WAS endogenous promoter (WASp). In this assay, BM cells are harvested from C57BL6 mice, exposed to retroviral supernatants and cultured long-term. Derived lines are considered immortalized based on their ability to continue to grow in vitro for more than 6 weeks in the presence of interleukin-3 and stem cell factor. To date, MLV and SIN transduction of 123 and 132 cultures, respectively, gave rise to 48 and 43 immortalized lines (39.0% and 32.6% immortalization rate). The difference in immortalization rate between MLV and SIN vectors was not statistically significant (Chi square: p=0.30). As expected, immortalized cells were negative/low for IgER, cKit and Sca1 expression, and positive to different degrees for expression of the myeloid markers CD11b/Mac1 and Ly6g/Gr1. Transduction of 114 and 62 cultures with LV and FV vectors, respectively, resulted in no immortalized lines. Real-time PCR was performed to evaluate transduction efficiency of bone marrow cells and immortalized lines. Integrated vector sequences in bone marrow cells transduced by LV and FV were detected in significantly higher quantities than in cells transduced with MLV and SIN vectors. However, expression of the EGFP transgene was markedly reduced in LV- and FV-transduced cells compared to cells exposed to MLV vectors (MFI: 14.0, 1.88, 93.2, respectively). These preliminary results confirm that gamma-retroviral gene transfer vectors are prone to causing immortalization of hematopoietic cells and suggest the vectors based on LV and FV backbones may be safer alternatives for WAS and other genetic disorders, provided that effective gene expression levels can be achieved in the biological model system under study.Table.Summary of immortalization results using MLV, SIN, LV and FV vectorsVirusMOITransduction efficiencyTransduction experiments% ImmortalizationMLV/UCOE/EGFP2067%5643MLV/WASp/EGFP2065%6736SIN/UCOE/EGFP532%7236SIN/WASp/EGFP537%6028LV/UCOE/EGFP1040%570LV/WASp/EGFP1049%570FV/UCOE/EGFP1027%280FV/WASp/EGFP1022%340negativeN.A.N.A.720 Disclosures: No relevant conflicts of interest to declare.

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3

Boscolo, Sabrina, Francesca Mion, Marta Licciulli, Paolo Macor, Luca De Maso, Martina Brce, Michael N. Antoniou, Roberto Marzari, Claudio Santoro, and Daniele Sblattero. "Simple scale-up of recombinant antibody production using an UCOE containing vector." New Biotechnology 29, no. 4 (May 2012): 477–84. http://dx.doi.org/10.1016/j.nbt.2011.12.005.

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4

Zhang, Fang, Susannah I. Thornhill, Steven J. Howe, Meera Ulaganathan, Axel Schambach, Joanna Sinclair, Christine Kinnon, H. Bobby Gaspar, Michael Antoniou, and Adrian J. Thrasher. "Lentiviral vectors containing an enhancer-less ubiquitously acting chromatin opening element (UCOE) provide highly reproducible and stable transgene expression in hematopoietic cells." Blood 110, no. 5 (September 1, 2007): 1448–57. http://dx.doi.org/10.1182/blood-2006-12-060814.

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AbstractUbiquitously acting chromatin opening elements (UCOEs) consist of methylation-free CpG islands encompassing dual divergently transcribed promoters of housekeeping genes that have been shown to confer resistance to transcriptional silencing and to produce consistent and stable transgene expression in tissue culture systems. To develop improved strategies for hematopoietic cell gene therapy, we have assessed the potential of the novel human HNRPA2B1-CBX3 UCOE (A2UCOE) within the context of a self-inactivating (SIN) lentiviral vector. Unlike viral promoters, the enhancer-less A2UCOE gave rise to populations of cells that expressed a reporter transgene at a highly reproducible level. The efficiency of expression per vector genome was also markedly increased in vivo compared with vectors incorporating either spleen focus-forming virus (SFFV) or cytomegalovirus (CMV) promoters, suggesting a relative resistance to silencing. Furthermore, an A2UCOE-IL2RG vector fully restored the IL-2 signaling pathway within IL2RG-deficient human cells in vitro and successfully rescued the X-linked severe combined immunodeficiency (SCID-X1) phenotype in a mouse model of this disease. These data indicate that the A2UCOE displays highly reliable transcriptional activity within a lentiviral vector, largely overcoming insertion-site position effects and giving rise to therapeutically relevant levels of gene expression. These properties are achieved in the absence of classic enhancer activity and therefore may confer a high safety profile.

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5

Pfaff, Nils, Nico Lachmann, Mania Ackermann, Saskia Kohlscheen, Christian Brendel, Michael Flasshove, Axel Schambach, and Thomas Moritz. "The Ubiquitous Chromatin Opening Element (UCOE) Enhances Lentiviral Cytidine Deaminase (CDD) Expression and Drug Resistance During Hematopoietic Differentiation of Murine Induced Pluripotent Stem Cells (iPSCs),." Blood 118, no. 21 (November 18, 2011): 4179. http://dx.doi.org/10.1182/blood.v118.21.4179.4179.

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Abstract Abstract 4179 Introduction: Transfer of drug resistance genes to the hematopoietic system has been advocated for myeloprotection during anti-cancer chemotherapy, however, for malignancies manifestated in blood or bone marrow compartments this strategy carries the risk of inadvertent transduction of tumor cells. Hematopoietic differentiation of induced pluripotent stem cells (iPSCs) has the potential to overcome this problem, and we here have investigated this concept in the context of Cytidine Deaminase (CDD)-mediated myeloprotection. However, epigenetic silencing of transgenic promoter/enhancer elements during differentiation is a major drawback when using genetically modified iPSCs. Therefore, we have transduced iPSCs with lentiviral constructs overexpressing CDD from different constitutive promoter/enhancer elements and have investigated the effects of the ubiquitous chromatin opening element (UCOE) on transgene stability and CDD-mediated drug resistance in hematopoietically differentiated and naïve iPSCs. Materials/Methods: Murine iPSCs were transduced with 3rd-generation self-inactivating (SIN) lentiviral constructs overexpressing CDD and an IRES-coupled dTomato reporter from a truncated elongation factor 1α (EFS) or spleen focus-forming (SFFV) promoter/enhancer. Optionally, the UCOE site was cloned upstream of the respective promoter/enhancer. Transgene expression, Ara-C resistance and selection potential were investigated for naïve iPSCs and after differentiation along the hematopoietic lineage (d 0–8). Ara-C resistance was analyzed for colony-forming cells (d8-16). Expression of transgenic dTomato and CDD was measured by FACS, western blot and qRT-PCR. Bisulfite sequencing was performed to assess promoter methylation for the different lentiviral constructs. Results: Our studies demonstrated efficient transduction and stable EFS-driven CDD expression in undifferentiated iPSCs irrespective of the UCOE site. In contrast, SFFV-driven CDD expression was rapidly silenced. Although transgene expression levels were higher in UCOE.EFS.CDD- versus EFS.CDD-iPSCs (MFI: 89.5 vs 39.0), both, EFS.CDD- and UCOU.EFS.CDD-iPSCs were significantly protected against exposure to Ara-C (2000 nM/ 48 h) and were efficiently selected by continuous exposure to 2000 nM Ara-C (increase of dTomato+ cells from 5–8 % to 75–98 % within 16 days). No influence of CDD expression on iPSC morphology, growth characteristics, and expression of the pluripotency markers Oct4, Sox2, or Nanog was noted. Upon hematopoietic differentiation profound transgene silencing was observed in EFS.CDD-iPSCs. Silencing occurred during the first days of differentiation. Only 5–9% dTomato+ cells were observed on days 4 or 8, and reduced CDD expression levels were detected on days 4, 8, and 16 by Western blot and qRT-PCR analysis. Nevertheless, hematopoietic colony-forming units displayed significant resistance to Ara-C when compared to non-transduced controls. In contrast, UCOE.EFS.CDD-iPSCs only showed minor degrees of differentiation-induced transgene silencing with approx. 50% of the cells still expressing the dTomato transgene on day 8. Moreover, when subjected to clonogenic assays in the presence of 1000nM Ara-C, UCOE.EFS.CDD- in comparison to EFS.CDD-transduced cells exhibited significantly increased drug resistance (colony survival: 74±15 vs. 48±7%, p<0.05, n=3). In addition, bisulfite sequencing demonstrated significantly reduced CpG methylation in UCOE.EFS.CDD transduced cells upon hematopoietic differentiation. Conclusions: Our data suggest that Ara-C resistance in the hematopoietic system can be achieved by hematopoietic differentiation of CDD-overexpressing iPSCs. While EFS and SFFV promoter/enhancer elements upon hematopoietic differentiation are prone to epigenetic silencing, this may be overcome by the use of a UCOE element, which stabilizes transgene expression during hematopoietic differentiation and significantly reduces CpG methylation in regulatory elements of the provirus. Thus, our UCOE.EFS.CDD vector allows for long-term transgene expression in hematopoietic progeny of iPSCs, and hematopoietic differentiation of gene modified, patient-derived iPSCs may be suitable to increase the safety of drug resistance gene therapy in malignant diseases with manifestation in the hematopoietic system. Disclosures: No relevant conflicts of interest to declare.

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6

Brendel, Christian, Stefan Stein, Michael Antoniou, and Manuel Grez. "UCOE (ubiquitous chromatin opening element) mediates copy dependent expression of gp91phox in lentiviral vectors." Blood Cells, Molecules, and Diseases 40, no. 2 (March 2008): 257–58. http://dx.doi.org/10.1016/j.bcmd.2007.10.025.

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Hou, Jeff Jia Cheng, Ben S. Hughes, Matthew Smede, Kar Man Leung, Kara Levine, Susan Rigby, Peter P. Gray, and Trent P. Munro. "High-throughput ClonePix FL analysis of mAb-expressing clones using the UCOE expression system." New Biotechnology 31, no. 3 (May 2014): 214–20. http://dx.doi.org/10.1016/j.nbt.2014.02.002.

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8

Betts, Zeynep, Alexandra S. Croxford, and Alan J. Dickson. "Evaluating the interaction between UCOE and DHFR-linked amplification and stability of recombinant protein expression." Biotechnology Progress 31, no. 4 (April 8, 2015): 1014–25. http://dx.doi.org/10.1002/btpr.2083.

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Anakok, O. F., K. N. Bayindirli, and P. Kose. "Optimising the new ucoe models as higher direct transgene expression profile for effective gene therapy applications." Cytotherapy 23, no. 5 (May 2021): S151—S152. http://dx.doi.org/10.1016/s1465324921005284.

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Seymour, Brenda J., Swati Singh, Hannah M. Certo, Karen Sommer, Blythe D. Sather, Socheath Khim, Courtnee Clough, et al. "Effective, safe, and sustained correction of murine XLA using a UCOE-BTK promoter-based lentiviral vector." Molecular Therapy - Methods & Clinical Development 20 (March 2021): 635–51. http://dx.doi.org/10.1016/j.omtm.2021.01.007.

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Zhang, Fang, Amy R. Frost, Mike P. Blundell, Olivia Bales, Michael N. Antoniou, and Adrian J. Thrasher. "A Ubiquitous Chromatin Opening Element (UCOE) Confers Resistance to DNA Methylation–mediated Silencing of Lentiviral Vectors." Molecular Therapy 18, no. 9 (September 2010): 1640–49. http://dx.doi.org/10.1038/mt.2010.132.

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12

Betts, Zeynep, and Alan J. Dickson. "Assessment of UCOE on Recombinant EPO Production and Expression Stability in Amplified Chinese Hamster Ovary Cells." Molecular Biotechnology 57, no. 9 (June 19, 2015): 846–58. http://dx.doi.org/10.1007/s12033-015-9877-y.

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Pradhan, Ajoya Kumar, Mahendra Kumar Mohanty, and Sanjeeb Kumar Kar. "Techno-economic Evaluation of Stand-alone Hybrid Renewable Energy System for Remote Village Using HOMER-pro Software." International Journal of Applied Power Engineering (IJAPE) 6, no. 2 (August 1, 2017): 73. http://dx.doi.org/10.11591/ijape.v6.i2.pp73-88.

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The off-grid hybrid renewable energy generation system has lesser cost of energy with higher reliability when compared with solar Photovoltaic (PV) or wind energy system individually. The optimization design is worked out by reducing the Unit Cost Of Energy (UCOE) for different case studies and comparing the outcomes obtained by the use of HOMER-Pro (hybrid optimization model of electric renewable) software. The optimal cash flow analysis of hybrid energy system is based on the load patterns is discussed, solar irradiance (kW/m2) of site at proper latitude and longitude, wind speed and price of diesel, which is collected from a remote village in Khurda District, Odisha in India. Moreover, the optimization and sensitivity results of the system are find out by varying the input parameters like solar radiation, wind speed etc.

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Pradhan, Ajoya Kumar, Mahendra Kumar Mohanty, and Sanjeeb Kumar Kar. "Techno-Economic Evaluation of Stand-alone Hybrid Renewable Energy System for Remote Village Using HOMER-Pro Software." International Journal of Applied Power Engineering (IJAPE) 6, no. 2 (August 1, 2017): 74. http://dx.doi.org/10.11591/ijape.v6.i2.pp74-89.

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The off-grid hybrid renewable energy generation system has lesser cost of energy with higher reliability when compared with solar photovoltaic (PV) or wind energy system individually. The optimization design is worked out by reducing the unit cost of energy (UCOE) for different case studies and comparing the outcomes obtained by the use of HOMER-Pro (Hybrid Optimization Model of Electric Renewable) software. The optimal cash flow analysis of hybrid energy system is based on the load patterns is discussed, solar irradiance (kW/m2) of site at proper latitude and longitude, wind speed and price of diesel, which is collected from a remote village in Khurda District, Odisha in India. Moreover, the optimization and sensitivity results of the system are find out by varying the input parameters like solar radiation, wind speed etc.

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Allen, Marianne Lindahl, and Michael Antoniou. "Correlation of DNA Methylation with Histone Modifications Across the HNRPA2B1-CBX3 Ubiquitously-Acting Chromatin Open Element (UCOE)." Epigenetics 2, no. 4 (October 3, 2007): 227–36. http://dx.doi.org/10.4161/epi.2.4.5231.

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Dighe, Niraja, Maroun Khoury, Citra Mattar, Mark Chong, Mahesh Choolani, Jianzhu Chen, Michael N. Antoniou, and Jerry K. Y. Chan. "Long-Term Reproducible Expression in Human Fetal Liver Hematopoietic Stem Cells with a UCOE-Based Lentiviral Vector." PLoS ONE 9, no. 8 (August 12, 2014): e104805. http://dx.doi.org/10.1371/journal.pone.0104805.

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Dharshanan, Suba, Heilly Chong, Swee Hung Cheah, and Zulkeflie Zamrod. "Stable expression of H1C2 monoclonal antibody in NS0 and CHO cells using pFUSE and UCOE expression system." Cytotechnology 66, no. 4 (July 24, 2013): 625–33. http://dx.doi.org/10.1007/s10616-013-9615-x.

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Yu-cheng Kao, Vincent, Sonia Ferreira, Simon N. Waddington, and Michael N. Antoniou. "Haemophilia B Curative FIX Production from a Low Dose UCOE-based Lentiviral Vector Following Hepatic Pre-natal Delivery." Current Gene Therapy 16, no. 4 (December 16, 2016): 231–41. http://dx.doi.org/10.2174/1566523216666161102150101.

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Saunders, Fay, Berni Sweeney, Michael N. Antoniou, Paul Stephens, and Katharine Cain. "Chromatin Function Modifying Elements in an Industrial Antibody Production Platform - Comparison of UCOE, MAR, STAR and cHS4 Elements." PLOS ONE 10, no. 4 (April 7, 2015): e0120096. http://dx.doi.org/10.1371/journal.pone.0120096.

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Cullmann, Katharina, Kaj E. C. Blokland, Attila Sebe, Franziska Schenk, Zoltán Ivics, Niels Heinz, and Ute Modlich. "Sustained and regulated gene expression by Tet-inducible “all-in-one” retroviral vectors containing the HNRPA2B1-CBX3 UCOE®." Biomaterials 192 (February 2019): 486–99. http://dx.doi.org/10.1016/j.biomaterials.2018.11.006.

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Doan, Chinh Chung, Thanh Long Le, Nguyen Quynh Chi Ho, and Nghia Son Hoang. "Effects of ubiquitous chromatin opening element (UCOE) on recombinant anti-TNFα antibody production and expression stability in CHO-DG44 cells." Cytotechnology 74, no. 1 (October 23, 2021): 31–49. http://dx.doi.org/10.1007/s10616-021-00503-1.

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Watson, Carole S., Rachel Schaefer, Susan E. White, Jacobus H. Homan, Laurence Fraher, Richard Harding, and Alan D. Bocking. "Effect of intermittent umbilical cord occlusion on fetal respiratory activity and brain adenosine in late-gestation sheep." Reproduction, Fertility and Development 14, no. 1 (2002): 35. http://dx.doi.org/10.1071/rd01013.

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It was hypothesized that intermittent umbilical cord occlusion (UCO) would inhibit ovine fetal breathing movements (FBM) in association with increased cerebral adenosine levels. To test this hypothesis, on two successive days during late gestation (133–134 days; term = 146 days), microdialysis samples were collected from the brains of 10 chronically instrumented fetal sheep during 2-h periods of complete UCO induced every 30 min (Day 1: 2-min UCOs; Day 2: 4-min UCOs). Control fetuses (n = 10) underwent no UCO. Tracheal pressure was measured throughout. This regimen resulted in a decrease in fetal arterial PO2 (PaO2) during each UCO to 7.3 0.8 mmHg (P<0.01; Day 1) and 8.4 1.1 mmHg (P<0.01; Day 2). Throughout each UCO period, fetal arterial pH (pHa) decreased to 7.28 0.02 (P<0.01; Day 1) and 7.11 0.07 (P<0.01; Day 2). The hourly incidence of FBM decreased significantly only on Day 2, from 38.6 4.1% to 4.1 1.6% (P<0.01). The frequency of deep isolated inspiratory efforts increased from 4.7 2.0 h–1 to 17.6 6.1 h–1 (P<0.05; Day 1) and from 2.2 0.9 h–1 to 33.6 4 h–1 (P<0.01; Day 2). The amplitude of both FBM and deep isolated inspiratory efforts increased during the UCO periods on both days. The concentration of cerebral extracellular fluid (ECF) adenosine during UCO increased by 219 215% (P<0.05; Day 1) and 172 107% (P<0.05; Day 2) over the baseline periods. In conclusion, the severity of the inhibitory effect of repeated UCO on FBM depends, in part, on the length of the occlusions. The inhibition of FBM during intermittent UCO may be mediated by the increase in ECF adenosine in the fetal brain. Furthermore, FBM and deep isolated inspiratory efforts appear to be regulated by different mechanisms.

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Lear, Christopher A., Laura Bennet, Benjamin A. Lear, Jenny A. Westgate, and Alistair J. Gunn. "Lack of evidence for impaired preload or Bezold-Jarisch activation during brief umbilical cord occlusions in fetal sheep." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 320, no. 4 (April 1, 2021): R532—R540. http://dx.doi.org/10.1152/ajpregu.00357.2020.

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Impaired cardiac preload secondary to umbilical cord occlusion (UCO) has been hypothesized to contribute to intrapartum decelerations, brief falls in fetal heart rate (FHR), through activation of the Bezold-Jarisch reflex. This cardioprotective reflex increases parasympathetic and inhibits sympathetic outflows triggering hypotension, bradycardia, and peripheral vasodilation, but its potential to contribute to intrapartum decelerations has never been systematically examined. In this study, we performed bilateral cervical vagotomy to remove the afferent arm and the efferent parasympathetic arm of the Bezold-Jarisch reflex. Twenty-two chronically instrumented fetal sheep at 0.85 of gestation received vagotomy ( n = 7) or sham vagotomy (control, n = 15), followed by three 1-min complete UCOs separated by 4-min reperfusion periods. UCOs in control fetuses were associated with a rapid fall in FHR and reduced femoral blood flow mediated by intense femoral vasoconstriction, leading to hypertension. Vagotomy abolished the rapid fall in FHR ( P < 0.001) and, despite reduced diastolic filling time, increased both carotid ( P < 0.001) and femoral ( P < 0.05) blood flow during UCOs, secondary to carotid vasodilation ( P < 0.01) and delayed femoral vasoconstriction ( P < 0.05). Finally, vagotomy was associated with an attenuated rise in cortical impedance during UCOs ( P < 0.05), consistent with improved cerebral substrate supply. In conclusion, increased carotid and femoral blood flows after vagotomy are consistent with increased left and right ventricular output, which is incompatible with the hypothesis that labor-like UCOs impair ventricular filling. Overall, the cardiovascular responses to vagotomy do not support the hypothesis that the Bezold-Jarisch reflex is activated by UCO. The Bezold-Jarisch reflex is therefore mechanistically unable to contribute to intrapartum decelerations.

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Müller-Kuller, Uta, Mania Ackermann, Stephan Kolodziej, Christian Brendel, Jessica Fritsch, Nico Lachmann, Hana Kunkel, et al. "A minimal ubiquitous chromatin opening element (UCOE) effectively prevents silencing of juxtaposed heterologous promoters by epigenetic remodeling in multipotent and pluripotent stem cells." Nucleic Acids Research 43, no. 3 (January 20, 2015): 1577–92. http://dx.doi.org/10.1093/nar/gkv019.

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Green, LR, Y. Kawagoe, DJ Hill, BS Richardson, and VK Han. "The effect of intermittent umbilical cord occlusion on insulin-like growth factors and their binding proteins in preterm and near-term ovine fetuses." Journal of Endocrinology 166, no. 3 (September 1, 2000): 565–77. http://dx.doi.org/10.1677/joe.0.1660565.

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Intermittent umbilical cord compression with resultant fetal hypoxia can have a negative impact on fetal growth and development. Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are the most important regulators of fetal growth. In preterm (107-108 days of gestation) and near-term (128-131 days of gestation) ovine fetuses, we have determined the effect of intermittent umbilical cord occlusion (UCO) over a period of 4 days on the profile and expression of IGFs and IGFBPs. In experimental group animals (preterm n=7; near term n=7) UCOs were carried out by complete inflation of an occluder cuff (duration 90 s) every 30 min for 3-5 h each day, while control fetuses (preterm n=7; near term n=7) received no UCOs. Ewes were euthanized at the end of day 4, and fetal heart, lung, kidney, liver, skeletal muscle and placenta were collected. During UCOs, PO(2! ) fell (by approximately 13 mmHg), pH fell (by approximately 0.05) and PCO(2) increased (by approximately 7 mmHg), and changed to a similar extent in both preterm and near-term groups. In both preterm and near-term groups, there was no difference in fetal body or organ weight between UCO and control fetuses. No significant changes were observed in plasma IGF-I and -II concentrations or IGFBP-1, -2, -3 or -4 levels throughout the 4-day study at either gestational age. In the preterm group UCO fetuses, IGF-II mRNA (1.2-6.0 kb) levels were lower in fetal lung (33%, P<0.05), heart (54%, P<0.01) and skeletal muscle (29%, P<0.05), but there were no differences in IGF-I mRNA levels (7.3 kb); IGFBP-2 mRNA (1.5 kb) levels were lower in the right lobe of the liver (42%, P<0.05) and kidney (22%, P<0.01), but hig! her in the heart (72%, P<0.01), while IGFBP-4 (2.4 kb) levels were lower in skeletal muscle (21%, P<0.01). In the near-term group UCO fetuses, IGFBP-2 mRNA levels were greater in the placenta (39%, P<0.05). Thus, intermittent UCO as studied has a greater effect on the expression of genes encoding certain peptides of the fetal IGF system in selected tissues in preterm fetuses than that in near-term fetuses. Altered IGFBP-2 mRNA levels with reduced IGF-II mRNA levels in selected tissues may mediate changes in growth and/or differentiation that might become apparent if the length of the UCO study were extended.

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Sapee, Syazwana, Ahmad Fitri Yusop, Mohammad Nazri Mohd Jaafar, Rizalman Mamat, Wan Asma Ibrahim, Hazir Farouk, Norwazan Abdul Rahim, Ilyia Syafira Ab Razak, Muhammad Syahiran Abdul Malik, and Zhang Bo. "Synthesis of non-edible biodiesel from crude jatropha oil and used cooking oil." MATEC Web of Conferences 225 (2018): 06008. http://dx.doi.org/10.1051/matecconf/201822506008.

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This study focuses on a feasibility study of alternative nonedible crude oil such as jatropha and used cooking oil in biodiesel production. Crude jatropha oil (CJO) and used cooking oil (UCO) were converted to biodiesel using a two-step transesterification process with presents of acid-based and alkaline-based catalysts. Each three biodiesel blends (B5, B15 and B25) have been produced by blended with conventional diesel fuel (CDF). Determination of the fuel properties for each blend including CDF, Jatropha Methyl Ester (JME) and Used Cooking Oil Methyl Ester (UCOME) have been carried out. The average yield for jatropha and used cooking oil biodiesels production was 94.3% and 92% respectively. The increment of the percentage of JME or UCOME in its blends is proportional to fuels physical properties such as density, specific gravity, kinematic viscosity and surface tension, however inversely proportional to fuels calorific value. Based on the results of this study, it is acceptable to conclude that non-edible CJO and UCO are viable alternatives to edible oil as feedstock to renewable fuel in order to reduce the greenhouse gases produced.

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Lear, Christopher A., Michael J. Beacom, Michi Kasai, Jenny A. Westgate, Robert Galinsky, Shoichi Magawa, Etsuko Miyagi, Tomoaki Ikeda, Laura Bennet, and Alistair J. Gunn. "Circulating catecholamines partially regulate T-wave morphology but not heart rate variability during repeated umbilical cord occlusions in fetal sheep." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 319, no. 1 (July 1, 2020): R123—R131. http://dx.doi.org/10.1152/ajpregu.00026.2020.

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Fetal heart rate (FHR) variability (FHRV) and ST segment morphology are potential clinical indices of fetal well-being during labor. β-Adrenergic stimulation by circulating catecholamines has been hypothesized to contribute to both FHRV and ST segment morphology during labor, but this has not been tested during brief repeated fetal hypoxemia that is characteristic of labor. Near-term fetal sheep (0.85 gestation) received propranolol (β-adrenergic blockade; n = 10) or saline ( n = 7) 30 min before being exposed to three 2-min complete umbilical cord occlusions (UCOs) separated by 3-min reperfusions. T/QRS ratio was calculated throughout UCOs and reperfusion periods, and measures of FHRV (RMSSD, SDNN, and STV) were calculated between UCOs. During the baseline period, before the start of UCOs, propranolol was associated with reduced FHR, SDNN, and STV but did not affect RMSSD or T/QRS ratio. UCOs were associated with rapid FHR decelerations and increased T/QRS ratio; propranolol significantly reduced FHR during UCOs and was associated with a slower rise in T/QRS ratio during the first UCOs, without affecting the maximal rise or T/QRS ratio during the second and third UCO. Between UCOs propranolol reduced FHR and T/QRS ratio but did not affect any measure of FHRV. These data demonstrate that circulating catecholamines do not contribute to FHRV during labor-like hypoxemia. Furthermore, circulating catecholamines did not contribute to the major rise in T/QRS ratio during labor-like hypoxemia but may regulate T/QRS ratio between brief hypoxemia.

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Bruun, Nina, Juho Lehmusto, Jarl Hemming, Fiseha Tesfaye, and Leena Hupa. "Metal Rod Surfaces after Exposure to Used Cooking Oils." Sustainability 14, no. 1 (December 29, 2021): 355. http://dx.doi.org/10.3390/su14010355.

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Used cooking oils (UCOs) have a high potential as renewable fuels for the maritime shipping industry. However, their corrosiveness during storage and usage are some of the concerns yet to be investigated for addressing compatibility issues. Thus, the corrosion of steels and copper exposed to the UCOs was studied through the immersion of metal rods for different periods. The changes on the rod surfaces were analyzed with a scanning electron microscope (SEM). After the immersion, the copper concentration dissolved in the bio-oils was measured using inductively coupled plasma-optical emission spectrometry (ICP-OES). The free fatty acids and glycerides were analyzed using gas chromatography with flame ionization detection (GC-FID). The acid number (AN), water concentration, as well as density and kinematic viscosity of the bio-oils were determined with standard methods. The UCOs with the highest water content were corrosive, while the oils with lower water concentrations but higher ANs induced lower corrosion. After mixing two different UCOs, the metal corrosion decreased with an increasing concentration of the oil with lower corrosive properties. The lower corrosion properties were most likely due to the monounsaturated fatty acids, e.g., oleic acid in oils. These acids formed a barrier layer on the rod surfaces, thereby inhibiting the permeation of oxygen and water to the surface. Even adding 0.025 wt% of tert-butylamine decreased the corrosivity of UCO against polished steel rod. The results suggested that mixing several oil batches and adding a suitable inhibitor reduces the potential corrosive properties of UCOs.

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Ikawa, Yasuhiro, Toru Uchiyama, Guridevi Jayashree Jagadeesh, and Fabio Candotti. "Negative Control Region Is a Critical Element Of Insertional Oncogenesis After Gene Transfer Into Hematopoietic Progenitors With Moloney Murine Leukemia Viruses." Blood 122, no. 21 (November 15, 2013): 164. http://dx.doi.org/10.1182/blood.v122.21.164.164.

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Abstract Gene transfer into hematopoietic stem cells has been used successfully to treat a variety of human genetic diseases. Although protocols have shown positive clinical outcomes, the successes of clinical trials have been tempered by adverse events in which the use of gamma-retroviral vectors (GV) containing full-length long terminal repeats (LTRs) with strong enhancer activity increased transcription of cancer-related genes, and thereby contributed to development of leukemia. Assessing safety of integrating viral vectors for future clinical use is therefore of paramount importance. The negative control region (NCR) is a particularly well-conserved sequence among mammalian gamma-retroviruses with demonstrated regulating a transcription activity of GV in hematopoietic cells. This suggests that the NCR might play a crucial role of insertional oncogenesis after gene transfer into hematopoietic progenitors. In a series of safety studies of viral gene transfer constructs, we used an in vitro assay of murine bone marrow (BM) cell immortalization and compared the consequences of hematopoietic stem cell transduction with three different kinds of viral vectors, including Moloney murine leukemia virus- (MMLV), lentivirus- (LV), and foamy virus (FV)-based constructs. To evaluate critical elements for cell immortalization by MMLV vectors, we also tested four different MMLV LTR variants deleted of either 1) most of the two 75-bp repeats associated with the viral enhancer (delE1), 2) all of the two 75-bp repeats and the NCR (delE2), 3) only the NCR (delNCR), or 4) carrying a deleterious mutation of the NCR NFAT motif (ΔNFAT). All vectors carried an internal expression cassette including the eGFP gene under the control of a UCOE (ubiquitously acting chromatin opening element) promoter. In this assay, BM cells are harvested from C57BL6 mice, exposed to retroviral supernatants and cultured long-term. Derived lines are considered immortalized based on their ability to continue to grow in vitro for more than six weeks in the presence of interleukin-3 and stem cell factor. Real-time PCR was performed to verify comparable transduction efficiency of bone marrow cells by different vectors. In our analysis of MMLV LTR mutants, full-MMLV and delE1 transduction of 92 and 108 cultures, respectively, resulted in 37 and 37 immortalized lines (40% and 34% immortalization rate, respectively). The difference in immortalization rate between full-MMLV and delE1 was not statistically significant. Transductions using delE2-, delNCR- and ΔNFAT-carrying vectors of 60, 36 and 35 cultures resulted in 10, 3 and 10 immortalized lines (17%, 8.3% and 29% immortalization rate, respectively). The difference between the immortalization caused by delE1 and delE2 vectors was statistically significant (p<0.05). Moreover, the difference between the immortalization caused by full-MMLV and delNCR vectors was statistically significant (p<0.01), while there was no significant difference between the immortalization induced by full-MMLV and ΔNFAT vectors. Transduction of 57 and 34 cultures with LV and FV vectors, respectively, resulted in no immortalized lines. Transductions of 128 cultures with a LV construct carrying the U3 region from the murine stem cell virus LTR as an internal promoter (LV-U3) resulted in 2 immortalized lines which was not statistically different from the results obtained with LV vectors carrying the UCOE internal promoter. These results confirm that GV are prone to causing immortalization of hematopoietic cells and indicate that deletion of the whole viral enhancer sequences may not be adequate to eliminate the insertional oncogenesis risk. Importantly, our data point to the NCR as a crucial element for immortalization and justify additional studies to evaluate its specific role in MMLV-mediated insertional oncogenesis. Finally, our results suggest that vectors based on LV and FV backbones are safer alternatives for clinical gene transfer into hematopoietic stem cells. Disclosures: No relevant conflicts of interest to declare.

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Borges, Alessandra Buhler, Carlos Rocha Gomes Torres, Graziela Ribeiro Batista, Eduardo Bresciani, Erica Crastechini, and Rayssa Ferreira Zanatta. "Bond Strength of Reline Resins to Aged-simulated Denture Base Acrylic Resin." World Journal of Dentistry 7, no. 1 (2016): 1–5. http://dx.doi.org/10.5005/jp-journals-10015-1353.

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ABSTRACT Objectives The aim of this study was to evaluate the bond strength of different direct reliners to acrylic resin for denture base. Materials and methods Double-cone specimens were made: HA-heat-cured acrylic resin-(n = 20); U-Ufi Gel Hard C-(n = 10); K: Kooliner-(n = 10); R-Rebase II Fast-(n = 10) and RH-Rebase II Fast + Resin Hardener-(n = 10). Ten HA samples were immediately submitted to cohesive test. The remaining HA samples and others were submitted to thermal aging (HAaged, 1000 cycles, 5.55oC), followed by tensile test. For tensile strength, 50 single cone-shaped samples were made of heat-cured acrylic resin and aged (HAaged, 1000 cycles, 5.55oC). After surface treatment, relining resin cones were build up using silicon molds, and stressed to failure. Values of cohesive and tensile strength were submitted to one-way ANOVA and Tukey's test (α = 5%). Results Bond strength were: HA/HAaged: 21.17 (Â±4.89)a, U/HAaged: 11.56 (Â±1.98)b, R/HAaged: 9.69 (Â±2.37)b, RH/ HAaged: 9.38 (Â±1.78)bc and K/HAaged: 5.98 (Â±1.90)c. The cohesive strength were: KCoe: 22.29(Â±4.06)a; RCoe: 23.99 (Â±3.29)a; RHCoe: 24.84 (Â±3.88)a; UCoe: 25.62 (Â±3.03)a; HAaged: 36.06 (Â±8.65)b and HA:42.29 (Â±7.68)b. Groups followed by the same letters do not show differences. Conclusion Bond strength of acrylic resin to acrylic denture base material is higher than the reliners and Ufi Gel Hard C showed the higher bond strength. How to cite this article Zanatta RF, Batista GR, Crastechini É, Bresciani E, Borges AB, Torres CRG. Bond Strength of Reline Resins to Aged-simulated Denture Base Acrylic Resin. World J Dent 2016;7(1):1-5.

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Lear, Christopher A., Jenny A. Westgate, Michi Kasai, Michael J. Beacom, Yoshiki Maeda, Shoichi Magawa, Etsuko Miyagi, Tomoaki Ikeda, Laura Bennet, and Alistair J. Gunn. "Parasympathetic activity is the key regulator of heart rate variability between decelerations during brief repeated umbilical cord occlusions in fetal sheep." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 319, no. 5 (November 1, 2020): R541—R550. http://dx.doi.org/10.1152/ajpregu.00186.2020.

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Fetal heart rate variability (FHRV) is a widely used index of intrapartum well being. Both arms of the autonomic system regulate FHRV under normoxic conditions in the antenatal period. However, autonomic control of FHRV during labor when the fetus is exposed to repeated, brief hypoxemia during uterine contractions is poorly understood. We have previously shown that the sympathetic nervous system (SNS) does not regulate FHRV during labor-like hypoxia. We therefore investigated the hypothesis that the parasympathetic system is the main mediator of intrapartum FHRV. Twenty-six chronically instrumented fetal sheep at 0.85 of gestation received either bilateral cervical vagotomy ( n = 7), atropine sulfate ( n = 7), or sham treatment (control, n = 12), followed by three 1-min complete umbilical cord occlusions (UCOs) separated by 4-min reperfusion periods. Parasympathetic blockade reduced three measures of FHRV before UCOs (all P < 0.01). Between UCOs, atropine and vagotomy were associated with marked tachycardia (both P < 0.005), suppressed measures of FHRV (all P < 0.01), and abolished FHRV on visual inspection compared with the control group. Tachycardia in the atropine and vagotomy groups resolved over the first 10 min after the final UCO, in association with evidence that the SNS contribution to FHRV progressively returned during this time. Our findings support that SNS control of FHRV is acutely suppressed for at least 4 min after a deep intrapartum deceleration and takes 5–10 min to recover. The parasympathetic system is therefore likely to be the key mediator of FHRV once frequent FHR decelerations are established during labor.

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Izmaylov, M., D. Rafaja, V. Sechovský, and A. V. Andreev. "Ferromagnetism in UCo1−xMnxAl and UCo1−xVxAl." Czechoslovak Journal of Physics 52, S1 (January 2002): A269—A272. http://dx.doi.org/10.1007/s10582-002-0065-5.

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Nikishina, Olga, and Olga Nikishina. "Incomplete construction: Russian and foreign experience." MATEC Web of Conferences 212 (2018): 04007. http://dx.doi.org/10.1051/matecconf/201821204007.

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The study is devoted to the objects of unfinished construction (hereinafter - UCO). The problem of the UCOs is urgent both for the regions and for the Russian Federation as a whole. The main reasons for the large number of the unfinished construction objects are analyzed in the paper. The global experience of solving the issue of long-term construction is considered. The unfinished objects spoil the architectural outlook of the city, while the lands are used inefficiently and the necrosis of capital occurs. In Russia, as a rule, conservation of these objects is not done that creates a real threat to life and health of people. The state and society cannot count on the economic effect of these objects, and they do not justify the goals and the means invested in them. Based on the conclusions drawn, measures are proposed that will allow preventing the suspension of the objects under construction at the moment, and complete the construction of the objects that begun earlier.

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Arponen, Milja, Eeva-Christine Brockmann, Riku Kiviranta, Urpo Lamminmäki, and Kaisa K. Ivaska. "Recombinant Antibodies with Unique Specificities Allow for Sensitive and Specific Detection of Uncarboxylated Osteocalcin in Human Circulation." Calcified Tissue International 107, no. 6 (August 24, 2020): 529–42. http://dx.doi.org/10.1007/s00223-020-00746-8.

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Abstract Osteocalcin is a bone-specific protein which contains three glutamic acid residues (Glu) that undergo post-translational gamma-carboxylation. Uncarboxylated osteocalcin (ucOC) may participate in the regulation of glucose metabolism, thus measurement of ucOC could be useful in evaluating interactions between bone and glucose metabolism. We developed recombinant antibodies and immunoassay to specifically detect ucOC in human blood samples. ucOC-specific recombinant antibodies were selected from an antibody library by phage display. Four candidates were characterized, and one (Fab-AP13) was used to set up an immunoassay with a pre-existing MAb. Plasma ucOC levels were measured in subjects with normal fasting blood glucose (≤ 6 mmol/l, N = 46) or with hyperglycemia (≥ 7 mmol/l, N = 29). Further, we analyzed ucOC in age- and gender-matched patients with diagnosed type 2 diabetes (T2D, N = 49). Antibodies recognized ucOC without cross-reaction to carboxylated osteocalcin. Antibodies had unique binding sites at the carboxylation region, with Glu17 included in all epitopes. Immunoassay was set up and characterized. Immunoassay detected ucOC in serum and plasma, with on average 1.6-fold higher levels in plasma. ucOC concentrations were significantly lower in subjects with hyperglycemia (median 0.58 ng/ml, p = 0.008) or with T2D diagnosis (0.68 ng/ml, p = 0.015) than in subjects with normal blood glucose (1.01 ng/ml). ucOC negatively correlated with fasting plasma glucose in subjects without T2D (r = − 0.24, p = 0.035) but not in T2D patients (p = 0.41). Our immunoassay, based on the novel recombinant antibody, allows for specific and sensitive detection of ucOC in human circulation. Correlation between ucOC and plasma glucose suggests interactions between osteocalcin and glucose metabolism in humans.

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Tacey, Alexander, Cassandra Smith, Mary N. Woessner, Paul Chubb, Christopher Neil, Gustavo Duque, Alan Hayes, Anthony Zulli, and Itamar Levinger. "Undercarboxylated osteocalcin is associated with vascular function in female older adults but does not influence vascular function in male rabbit carotid artery ex vivo." PLOS ONE 15, no. 11 (November 25, 2020): e0242774. http://dx.doi.org/10.1371/journal.pone.0242774.

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Background There are conflicting reports on the association of undercarboxylated osteocalcin (ucOC) in cardiovascular disease development, including endothelial function and hypertension. We tested whether ucOC is related to blood pressure and endothelial function in older adults, and if ucOC directly affects endothelial-mediated vasodilation in the carotid artery of rabbits. Methods In older adults, ucOC, blood pressure, pulse wave velocity (PWV) and brachial artery flow-mediated dilation (BAFMD) were measured (n = 38, 26 post-menopausal women and 12 men, mean age 73 ± 0.96). The vasoactivity of the carotid artery was assessed in male New Zealand White rabbits following a four-week normal or atherogenic diet using perfusion myography. An ucOC dose response curve (0.3–45 ng/ml) was generated following incubation of the arteries for 2-hours in either normal or high glucose conditions. Results ucOC levels were higher in normotensive older adults compared to those with stage 2 hypertension (p < 0.05), particularly in women (p < 0.01). In all participants, higher ucOC was associated with lower PWV (p < 0.05), but not BAFMD (p > 0.05). In rabbits, ucOC at any dose did not alter vasoactivity of the carotid artery, either following a normal or an atherogenic diet (p > 0.05). Conclusion Increased ucOC is associated with lower blood pressure and increased arterial stiffness, particularly in post-menopausal women. However, ucOC administration has no direct short-term effect on endothelial function in rabbit arteries. Future studies should explore whether treatment with ucOC, in vivo, has direct or indirect effects on blood vessel function.

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Liu, Xiaoying, Bu B. Yeap, Kaye E. Brock, Itamar Levinger, Jonathan Golledge, Leon Flicker, and Tara C. Brennan-Speranza. "Associations of Osteocalcin Forms With Metabolic Syndrome and Its Individual Components in Older Men: The Health In Men Study." Journal of Clinical Endocrinology & Metabolism 106, no. 9 (May 18, 2021): e3506-e3518. http://dx.doi.org/10.1210/clinem/dgab358.

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Abstract Context The osteoblast-derived polypeptide, osteocalcin (OC), has been associated with lower risk of type 2 diabetes and metabolic syndrome (MetS) in several epidemiological studies. Animal studies have indicated the undercarboxylated form of OC (ucOC) drives its association with metabolic outcomes. Objective We compared associations of ucOC and carboxylated OC (cOC) with MetS and its components in older men. Methods A cross-sectional analysis of 2575 men aged ≥70 years and older resident in Perth, Western Australia. ucOC was assayed using a hydroxyapatite-binding method, and cOC calculated by subtracting ucOC from total OC. Main outcome measures were MetS and its components. Results Both lower serum ucOC and cOC levels, and the proportion of cOC (%cOC) were associated with less favorable metabolic parameters (higher waist circumference, triglyceride, glucose, blood pressure, and lower high-density lipoprotein cholesterol), whereas inverse associations were found with %ucOC. Men in the lowest quintile of ucOC had higher risk of MetS compared to men in the highest quintile (Q1 ≤ 7.7 vs Q5 > 13.8 ng/mL; OR = 2.4; 95% CI, 1.8-3.2). Men in the lowest quintile of cOC had higher risk of MetS compared to those in the highest quintile (≤ 5.8 vs > 13.0 ng/mL; OR = 2.4; 95% CI, 1.8-3.2). Conclusion Lower concentrations of serum ucOC or cOC were associated with less favorable metabolic parameters and a higher risk of MetS. In contrast, a lower proportion of ucOC was associated with better metabolic parameters and lower MetS risk. Further research is warranted to determine whether ucOC and cOC are suitable biomarkers for cardiometabolic risk in men.

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McKenzie, Amy L., and Lawrence E. Armstrong. "Monitoring Body Water Balance in Pregnant and Nursing Women: The Validity of Urine Color." Annals of Nutrition and Metabolism 70, Suppl. 1 (2017): 18–22. http://dx.doi.org/10.1159/000462999.

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Background: Urine osmolality (UOSM) reflects the renal regulation of excess fluid or deficit fluid, and therefore, serves as a marker of hydration status. Little is known about monitoring hydration in pregnant and lactating women despite significant physiological challenges to body water balance during that time. Therefore, we designed a study to assess if urine color (UCOL), an inexpensive and practical method, was a valid means of assessing urine concentration. Twenty-four hour UCOL was significantly correlated with 24 h UOSM in all women: pregnant, lactating, and control (r = 0.61-0.84, all p < 0.001). Utilizing a receiver operating characteristic statistical analysis, we found that 24 h and single sample UCOL had excellent diagnostic accuracy for identifying UOSM ≥500 mOsm·kg-1 in all women (area under the curve = 0.68-0.95, p < 0.001-0.46), and the UCOL that reflected this cut off was ≥4 on the UCOL chart. Summary: Therefore, UCOL is a valid marker of urine concentration and ultimately hydration status in pregnant, lactating, and non-pregnant, non-lactating women. For pregnant, lactating, and control women, the UCOL chart is a valid tool that can be used to monitor urine concentration in a single sample or over the course of the day via a 24 h sample. Key Message: Women who present with a UCOL of 4 or more likely have a UOSM ≥500 mOsm·kg-1. Given the positive health benefits associated with UOSM <500 mOsm·kg-1, women should aim for a 1, 2, or 3 on the UCOL chart. If a UCOL of ≥4 is observed, women should consider increasing fluid consumption to improve hydration status.

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Nimptsch, Katharina, Alexandra Nieters, Susanne Hailer, Günther Wolfram, and Jakob Linseisen. "The association between dietary vitamin K intake and serum undercarboxylated osteocalcin is modulated by vitamin K epoxide reductase genotype." British Journal of Nutrition 101, no. 12 (November 25, 2008): 1812–20. http://dx.doi.org/10.1017/s0007114508131750.

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Vitamin K acts as a cofactor during the γ-carboxylation of vitamin K-dependent proteins. Undercarboxylated osteocalcin (ucOC) is a suggested biomarker of vitamin K status. The +2255 polymorphism of the vitamin K epoxide reductase gene (VKORC1) was shown to be associated with the recycling rate of the active form of vitamin K. We investigated the association between dietary vitamin K intake and serum ucOC and hypothesized that this association might vary byVKORC1genotype. ucOC and total intact osteocalcin (iOC) concentrations were quantified using specific ELISA tests in serum samples of 548 male and female participants (aged 18–81 years) of the Bavarian Food Consumption Survey II. ucOC was expressed relative to iOC (ucOC/iOC ratio). Dietary intake of vitamin K (phylloquinone and menaquinones) was estimated from three 24 h dietary recalls using previously published food composition data. The association between dietary vitamin K intake and ucOC/iOC ratio was analysed using linear and non-linear regression models. Median intakes of phylloquinone/menaquinones were 83·4/37·6 μg/d in men and 79·6/29·8 μg/d in women, respectively. As expected, vitamin K intake was significantly inversely associated with the ucOC/iOC ratio. The ucOC/iOC ratio differed significantly across variants of the +2255 polymorphism in theVKORC1gene. Stratification byVKORC1+2255 genotype revealed that only in carriers of the GG genotype (39 % of all participants) did the ucOC/iOC ratio significantly decrease with increasing intake of vitamin K. Thus, the results show that the inverse association between dietary vitamin K intake and serum ucOC depends on a functionally relevant allelic variant of theVKORC1gene.

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Yang, Jianjian, Changsong Xie, Qianqian Yang, Shuang Wang, Yun Gao, Jiahui Ji, Zecheng Du, Zixi Kang, Rongming Wang, and Daofeng Sun. "PANa/Covalent organic framework composites with improved water uptake and proton conductivity." Chemical Communications 58, no. 8 (2022): 1131–34. http://dx.doi.org/10.1039/d1cc06010d.

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In this communication, we construct composite-type PANa@UCOF-x by the in situ reaction strategy, which combines the advantages of UCOF with ordered channels and PANa with high water uptake, thus improving the proton conductivity of UCOF.

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Ellis, Lindsay A., Brandon A. Yates, Amy L. McKenzie, Colleen X. Muñoz, Douglas J. Casa, and Lawrence E. Armstrong. "Effects of Three Oral Nutritional Supplements on Human Hydration Indices." International Journal of Sport Nutrition and Exercise Metabolism 26, no. 4 (August 2016): 356–62. http://dx.doi.org/10.1123/ijsnem.2015-0244.

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Urine color (Ucol) as a hydration assessment tool provides practicality, ease of use, and correlates moderately to strongly with urine specific gravity (Usg) and urine osmolality (Uosm). Indicative of daily fluid turnover, along with solute and urochrome excretion in 24-hr samples, Ucol may also reflect dietary composition. Thus, the purpose of this investigation was to determine the efficacy of Ucol as a hydration status biomarker after nutritional supplementation with beetroot (880 mg), vitamin C (1000 mg), and riboflavin (200 mg). Twenty males (Mean ± SD; age, 21 ± 2 y; body mass, 82.12 ± 15.58 kg; height, 1.77 ± 0.06 m) consumed a standardized breakfast and collected all urine voids on one control day (CON) and 1 day after consuming a standardized breakfast and a randomized and double-blinded supplement (SUP) over 3 weeks. Participants replicated exercise and diet for one day before CON, and throughout CON and SUP. Ucol, Usg, Uosm, and urine volume were measured in all 24-hr samples, and Ucol and Usg were measured in all single samples. Ucol was a significant predictor of single sample Usg after all supplements (p < .05). Interestingly, 24-hr Ucol was not a significant predictor of 24-h Usg and Uosm after riboflavin supplementation (p = .20, p = .21). Further, there was a significant difference between CON and SUP 24-h Ucol only after riboflavin supplementation (p < .05). In conclusion, this investigation suggests that users of the UCC (urine color chart) should consider riboflavin supplementation when classifying hydration status and use a combination of urinary biomarkers (e.g., Usg and Ucol), both acutely and over 24 hr.

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Gasparini, A., Y. K. Huang, N. T. Huy, J. C. P. Klaasse, T. Naka, E. Slooten, and A. de Visser. "The Superconducting Ferromagnet UCoGe." Journal of Low Temperature Physics 161, no. 1-2 (June 18, 2010): 134–47. http://dx.doi.org/10.1007/s10909-010-0188-1.

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Dong, Jae-June, Jay J. Shen, and Yong-Jae Lee. "Dose-Dependent Effect of Cotinine-Verified Tobacco Smoking on Serum Immunoglobulin E Levels in Korean Adult Males." Nicotine & Tobacco Research 21, no. 6 (November 6, 2017): 813–17. http://dx.doi.org/10.1093/ntr/ntx247.

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Abstract Background Smoking is one of the risk factors to exacerbate allergic diseases, and it may affect serum immunoglobulin E (IgE) levels. However, few studies have relied on an objective biomarker to examine the effect of tobacco smoking on serum IgE levels. Method A nationwide cross-sectional study was conducted to examine the relationship between urinary cotinine (Ucot) concentrations and IgE levels in 973 males using data from the 2010 Korean National Health and Nutrition Examination Survey (KNHANES). Ucot was classified into four groups based on concentration (ng/mL) as follows: nonsmoker group (Ucot <50 ng/mL) and three tertile groups in smokers (T1 [Ucot: 50.00–921.28 ng/mL]; T2 [Ucot: 921.29–1869.36 ng/mL]; and T3 [Ucot ≥1869.37 ng/mL]). The dose-response relationships between Ucot concentrations and total serum IgE level were estimated using analysis of covariance (ANCOVA) and multiple linear regression analysis after adjusting for confounding variables. Results We found a significant and positive dose-related effect of cigarette smoking as measured by Ucot concentrations on the total serum IgE level. The multivariate adjusted means of total serum IgE levels (SE) were 321.0 (36.3), 404.4 (102.7), 499.2 (79.2), and 534.7 (82.7) IU/mL, after adjusting for age, body mass index, alcohol ingestion, physical exercise, job, and household income. The regression coefficient β for total serum IgE was β = 68.6 with increasing level of Ucot group after adjusting for the same covariables (p = .009). Conclusion These findings suggest that the amount of smoking may have a dose-dependent effect on total serum IgE levels. Implication Smoking is one of the risk factors to exacerbate allergic diseases, and it may affect serum immunoglobulin E (IgE) levels, which is closely related to type 1 mediated allergic diseases. However, few studies have relied on an objective biomarker to examine the effect of tobacco smoking on serum IgE levels. We found that tobacco exposure, as measured by Ucot concentrations, increased the serum IgE levels in a dose-response manner in a representative sample of Korean adult males.

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FUJINO, Masato, Kazuo SHINOZAKI, Yukikazu NATORI, and Kazuhisa OHTAGUCHI. "The concept of UCEE Researcher Database." Journal of Information Processing and Management 50, no. 5 (2007): 266–79. http://dx.doi.org/10.1241/johokanri.50.266.

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Tacey, Alexander, Marc Sim, Cassandra Smith, Mary N. Woessner, Elizabeth Byrnes, Joshua R. Lewis, Tara Brennan-Speranza, Jonathan M. Hodgson, Lauren C. Blekkenhorst, and Itamar Levinger. "Association between Circulating Osteocalcin and Cardiometabolic Risk Factors following a 4-Week Leafy Green Vitamin K-Rich Diet." Annals of Nutrition and Metabolism 76, no. 5 (2020): 361–67. http://dx.doi.org/10.1159/000511660.

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Background: Evidence suggests that lower serum undercarboxylated osteocalcin (ucOC) may be negatively associated with cardiometabolic health. We investigated whether individuals with a suppression of ucOC following an increase in dietary vitamin K1 exhibit a relative worsening of cardiometabolic risk factors. Materials and Methods: Men (n = 20) and women (n = 10) aged 62 ± 10 years participated in a randomized, controlled, crossover study. The primary analysis involved using data obtained from participants following a high vitamin K1 diet (HK; 4-week intervention of increased leafy green vegetable intake). High and low responders were defined based on the median percent reduction (30%) in ucOC following the HK diet. Blood pressure (resting and 24 h), arterial stiffness, plasma glucose, lipid concentrations, and serum OC forms were assessed. Results: Following the HK diet, ucOC and ucOC/tOC were suppressed more (p < 0.01) in high responders (41 and 29%) versus low responders (12 and 10%). The reduction in ucOC and ucOC/tOC was not associated with changes in blood pressure, arterial stiffness, plasma glucose, or lipid concentrations in the high responders (p > 0.05). Discussion/Conclusion: Suppression of ucOC via consumption of leafy green vegetables has no negative effects on cardiometabolic health, perhaps, in part, because of cross-talk mechanisms.

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Halas, Helena. "Motivi za izobraževanje učiteljev. Zakaj se učitelji srednjih šol formalno dopolnilno izobražujejo." Andragoška spoznanja 10, no. 1 (December 1, 2004): 37–46. http://dx.doi.org/10.4312/as.10.1.37-46.

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V prispevku so podani rezultati raziskave motivov za formalno dopolnilno izobrazevanje srednjesolskih učiteljev. Avtorica skusa v clanku spodbijati ocitke učiteljem, da se večinoma izobrazujejo zaradi napredovanja v nazive in visje placilne razrede. V anketnem vprasalniku so ucitelji ocenjevali pomembnost dvanajstih motivov: vedozeljnost, osebnostna rast, uporabnost znanja, aktivno preiivljanje prostega casa, dober predavatelj, krepitev strokovne avtonomije, zelja po stikih z ljudmi, cas izvajanja izobrazevanja, zanimive ucne oblike in ucne metode, vpliv in ugled v druzbi, napotilo vodstva ter napredovanje v naziv in visji placilni razred. Rezultati kazejo, da v vzorcu izstopajo motivi, kot so uporabnost znanja, vedozeljnost, dober predavatelj ter zanimive ucne oblike in ucne metode.

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Colleluori, Georgia, Nicola Napoli, Uma Phadnis, Reina-Armamento Villareal, and Dennis T. Villareal. "Effect of Weight Loss, Exercise, or Both on Undercarboxylated Osteocalcin and Insulin Secretion in Frail, Obese Older Adults." Oxidative Medicine and Cellular Longevity 2017 (2017): 1–12. http://dx.doi.org/10.1155/2017/4807046.

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Background. Obesity exacerbates age-related decline in glucometabolic control. Undercarboxylated osteocalcin (UcOC) regulates pancreatic insulin secretion. The long-term effect of lifestyle interventions on UcOC and insulin secretion has not been investigated. Methods. One hundred seven frail, obese older adults were randomized into the control (N=27), diet (N=26), exercise (N=26), and diet-exercise (N=28) groups for 1 year. Main outcomes included changes in UcOC and disposition index (DI). Results. UcOC increased in the diet group (36 ± 11.6%) but not in the other groups (P<0.05 between groups). Although similar increases in DI occurred in the diet-exercise and diet groups at 6 months, DI increased more in the diet-exercise group (92.4 ± 11.4%) than in the diet group (61.9 ± 15.3%) at 12 months (P<0.05). UcOC and body composition changes predicted DI variation in the diet group only (R2=0.712), while adipocytokines and physical function changes contributed to DI variation in both the diet (∆R2=0.140 and 0.107) and diet-exercise (∆R2=0.427 and 0.243) groups (P<0.05 for all). Conclusions. Diet, but not exercise or both, increases UcOC, whereas both diet and diet-exercise increase DI. UcOC accounts for DI variation only during active weight loss, while adipocytokines and physical function contribute to diet-exercise-induced DI variation, highlighting different mechanisms for lifestyle-induced improvements in insulin secretion. This trial was registered with ClinicalTrials.gov number NCT00146107.

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Berisha-Muharremi, Venera, Vesna Kusec, and Ivana Pavlic-Renar. "Undercarboxylated Osteocalcin in Newly Diagnosed DM2 Patients after Blood Glucose Regulation." Problems of Endocrinology 62, no. 5 (September 22, 2016): 77. http://dx.doi.org/10.14341/probl201662577.

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Introduction. Recent in vitro and in vivo studies have suggested a role of undercarboxylated osteocalcin (ucOC), not total (TOC) osteocalcin in glucose and energy metabolism.Aims: to investigate the relationship of ucOC level and blood glucose (BG) control in newly diagnosed type 2 diabetes and its change with BG control improvement.Subjects and methods. Fifty seven newly diagnosed type 2 diabetic patients with no history of bone metabolism disturbances had two visits3 months apart, with physical examination and blood sampling. The patients had consultation about life style changes, no medication was prescribed on visit 1. Weekly (first month) and biweekly telephone contacts were performed to enhance compliance. Samples for parameters of BG metabolism and bone turnover were collected on visit 1 and 2. Standard automated or semi-automated methods were used for measurements, for ucOC the only available commercial kit.Results. Forty seven patients completed the study. Thirty two (56%) patients reached the target HbA1c (≤7%). No correlation of ucOC and HbA1c and FBG was observed. Median HbA1c and FBG changed significantly (8.0 to 6.5%; 9.0 to 7.0 mmol/L resp.; Wilcoxon signed rank test p<0.001), ucOC was slightly but not significantly lower (2.0 to 1.4 mcg/L; p=0.465). No correlation between differences in HbA1c and ucOC between Visits 1 and 2 was revealed. There was a significant change in HOMA%B but not HOMA IR, not correlated to ucOC.Conclusion. This study failed to prove the relationship between blood glucose regulation and ucOC level. However, it does not exclude it, so further research is needed. A lack of robust essay for human ucOC might explain inconclusive results of clinical studies. The fact that as much as 56% patients achieved the target HbA1c with no medication, challenges most BG control guidelines.

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Waruru, Anthony, Dickens Onyango, Lilly Nyagah, Alex Sila, Wanjiru Waruiru, Solomon Sava, Elizabeth Oele, et al. "Leading causes of death and high mortality rates in an HIV endemic setting (Kisumu county, Kenya, 2019)." PLOS ONE 17, no. 1 (January 20, 2022): e0261162. http://dx.doi.org/10.1371/journal.pone.0261162.

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Background In resource-limited settings, underlying causes of death (UCOD) often are not ascertained systematically, leading to unreliable mortality statistics. We reviewed medical charts to establish UCOD for decedents at two high volume mortuaries in Kisumu County, Kenya, and compared ascertained UCOD to those notified to the civil registry. Methods Medical experts trained in COD certification examined medical charts and ascertained causes of death for 456 decedents admitted to the mortuaries from April 16 through July 12, 2019. Decedents with unknown HIV status or who had tested HIV-negative >90 days before the date of death were tested for HIV. We calculated annualized all-cause and cause-specific mortality rates grouped according to global burden of disease (GBD) categories and separately for deaths due to HIV/AIDS and expressed estimated deaths per 100,000 population. We compared notified to ascertained UCOD using Cohen’s Kappa (κ) and assessed for the independence of proportions using Pearson’s chi-squared test. Findings The four leading UCOD were HIV/AIDS (102/442 [23.1%]), hypertensive disease (41/442 [9.3%]), other cardiovascular diseases (23/442 [5.2%]), and cancer (20/442 [4.5%]). The all-cause mortality rate was 1,086/100,000 population. The highest cause-specific mortality was in GBD category II (noncommunicable diseases; 516/100,000), followed by GBD I (communicable, perinatal, maternal, and nutritional; 513/100,000), and III (injuries; 56/100,000). The HIV/AIDS mortality rate was 251/100,000 population. The proportion of deaths due to GBD II causes was higher among females (51.9%) than male decedents (42.1%; p = 0.039). Conversely, more men/boys (8.6%) than women/girls (2.1%) died of GBD III causes (p = 0.002). Most of the records with available recorded and ascertained UCOD (n = 236), 167 (70.8%) had incorrectly recorded UCOD, and agreement between notified and ascertained UCOD was poor (29.2%; κ = 0.26). Conclusions Mortality from infectious diseases, especially HIV/AIDS, is high in Kisumu County, but there is a shift toward higher mortality from noncommunicable diseases, possibly reflecting an epidemiologic transition and improving HIV outcomes. The epidemiologic transition suggests the need for increased focus on controlling noncommunicable conditions despite the high communicable disease burden. The weak agreement between notified and ascertained UCOD could lead to substantial inaccuracies in mortality statistics, which wholly depend on death notifications.

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Liu, Suifeng, Feng Gao, Lei Wen, Min Ouyang, Yi Wang, Qiong Wang, Liping Luo, and Zaijin Jian. "Osteocalcin Induces Proliferation via Positive Activation of the PI3K/Akt, P38 MAPK Pathways and Promotes Differentiation Through Activation of the GPRC6A-ERK1/2 Pathway in C2C12 Myoblast Cells." Cellular Physiology and Biochemistry 43, no. 3 (2017): 1100–1112. http://dx.doi.org/10.1159/000481752.

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Background/Aims: Sarcopenia is characterized by an age-related decline in skeletal muscle plus low muscle strength and/or physical performance. Despite the clinical significance of sarcopenia, the molecular pathways underlying sarcopenia remain elusive. The recent demonstration that undercarboxylated osteocalcin (ucOC) favours muscle function related to insulin sensitivity and glucose metabolism raises the question of whether this hormone may also regulate muscle mass. The present study explored the promotive effects of ucOC in proliferation and differentiation processes of C2C12 myoblasts as well as the possible signalling pathways involved. Methods: The effects of exogenous ucOC on C2C12 myoblasts proliferation were assessed using CCK8 and immunohistological staining assays. C2C12 cells were pretreated with PI3K/Akt or P38 MAPK inhibitors to investigate the possible involvement of the PI3K/Akt and P38 MAPK pathways in proliferation. The levels of Akt, phosphorylated-Akt (p-Akt), P38, and phosphorylated-P38 (p-P38) were measured by Western Blotting. The effects of ucOC on myoblast differentiation were quantified by morphological analysis. A silencing experiment was conducted in which the expression of GPRC6A in C2C12 myoblasts was modified. The expression of GPRC6A, myosin heavy chain (MyHC) and the related ERK1/2 signalling pathway in C2C12 myoblasts were monitored by qRT-PCR and Western Blotting. Results: We showed that treatment with exogenous ucOC stimulated the priming of C2C12 myoblasts proliferation. Inhibition of Akt phosphorylation by wortmannin or inhibition of P38 MAPK phosphorylation by SB203580 decreased C2C12 cell proliferation. Wortmannin also reduced P38 MAPK phosphorylation, whereas SB203580 did not affect Akt activation. Furthermore, ucOC promoted C2C12 myoblast differentiation. Inhibition of ERK1/2 phosphorylation with U0126 decreased C2C12 cell differentiation. Finally, GPRC6A expression was substantially increased after ucOC treatment of C2C12 cells. GPRC6A silencing inhibited Akt, P38 MAPK phosphorylation in C2C12 cells, and ERK1/2 phosphorylation in C2C12 myotubes; GPRC6A silencing also decreased cell proliferation, decreased cell differentiation, and downregulated MyHC expression. Conclusions: The present data suggest that ucOC induces myoblast proliferation via sequential activation of the PI3K/Akt and p38 MAPK pathways in C2C12 myoblast cells. Moreover, ucOC enhances myogenic differentiation via a mechanism involving GPRC6A-ERK1/2 signalling.

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Nguyen, Huy Thanh, Cuong Duc Dao, Thu Thanh Vu, and An Tu Bui. "ON DISCOVERY OF THE FERROMAGNETIC SUPERCONDUCTOR UCoGe." Science and Technology Development Journal 14, no. 2 (June 30, 2011): 21–28. http://dx.doi.org/10.32508/stdj.v14i2.1903.

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We report the coexistence of ferromagnetic order and superconductivity in UCoGe at ambient pressure. The data obtained from the basic thermal, magnetic and transport properties on the macro and microscopic scale show that UCoGe is a weak ferromagnet with a Curie temperature TC = 3 K, and also, is a superconductor with a resistive transition temperature Ts = 0.8 K. Those present evidence that UCoGe is an unconventional superconductor and argue that superconductivity is mediated by critical ferromagnetic spin fluctuations.

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Journal articles on the topic 'UCOE'

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