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Yoshichika Kawai, Erika Nuka
Reactive oxygen species and their reaction products can damage DNA to form mutagenic lesions. Among the reactive species, lipid peroxidation-derived aldehydes react with nucleobases and form bulky exocyclic adducts. Many types of aldehyde-derived DNA adducts have been characterized, identified and detected in vitro and in vivo, whereas relative quantitative and pathophysiological contributions of each adduct still remain unclear. In recent years, an abundant class of DNA adducts derived from 4-oxo-2-alkenals have been identified, in addition to classic aldehyde-derived adducts...
January 2018: Journal of Clinical Biochemistry and Nutrition
Sen Zheng, Jun-Ichi Nagao, Mami Nishie, Takeshi Zendo, Kenji Sonomoto
Lantibiotic nukacin ISK-1 is produced by Staphylococcus warneri ISK-1. The dual functional transporter NukT, an ABC transporter maturation and secretion protein, contributes to cleavage of the leader peptide from the prepeptide (modified NukA) and the final transport of nukacin ISK-1. NukT consists of an N-terminal peptidase domain (PEP), a C-terminal nucleotide-binding domain (NBD), and a transmembrane domain (TMD). In this study, NukT and its peptidase-inactive mutant were expressed, purified, and reconstituted into liposomes for analysis of their peptidase and ATPase activities...
January 2018: Applied Microbiology and Biotechnology
Robert D Finn, Teresa K Attwood, Patricia C Babbitt, Alex Bateman, Peer Bork, Alan J Bridge, Hsin-Yu Chang, Zsuzsanna Dosztányi, Sara El-Gebali, Matthew Fraser, Julian Gough, David Haft, Gemma L Holliday, Hongzhan Huang, Xiaosong Huang, Ivica Letunic, Rodrigo Lopez, Shennan Lu, Aron Marchler-Bauer, Huaiyu Mi, Jaina Mistry, Darren A Natale, Marco Necci, Gift Nuka, Christine A Orengo, Youngmi Park, Sebastien Pesseat, Damiano Piovesan, Simon C Potter, Neil D Rawlings, Nicole Redaschi, Lorna Richardson, Catherine Rivoire, Amaia Sangrador-Vegas, Christian Sigrist, Ian Sillitoe, Ben Smithers, Silvano Squizzato, Granger Sutton, Narmada Thanki, Paul D Thomas, Silvio C E Tosatto, Cathy H Wu, Ioannis Xenarios, Lai-Su Yeh, Siew-Yit Young, Alex L Mitchell
InterPro ( is a freely available database used to classify protein sequences into families and to predict the presence of important domains and sites. InterProScan is the underlying software that allows both protein and nucleic acid sequences to be searched against InterPro's predictive models, which are provided by its member databases. Here, we report recent developments with InterPro and its associated software, including the addition of two new databases (SFLD and CDD), and the functionality to include residue-level annotation and prediction of intrinsic disorder...
January 4, 2017: Nucleic Acids Research
Dai Inoue, Norihide Yoneda, Kotaro Yoshida, Hiromi Nuka, Jun Kinoshita, Sachio Fushida, Fumihito Toshima, Tetsuya Minami, Masayuki Takahira, Shoko Hamaoka, Hiroko Ikeda, Toshifumi Gabata, Mitsuhiro Kawano
We describe a 67-year-old man with immunoglobulin G4-related disease (IgG4-RD) presenting with optic neuropathy, dacryoadenitis, periaortitis, retroperitoneal fibrosis, and a gastric mass-like lesion. A mass-like lesion measuring 52 × 40 mm in the antrum of the stomach was found incidentally through whole-body screening for other organ involvement of IgG4-RD using contrast-enhanced computed tomography (CT). Histology of the stomach revealed that the lesion was also IgG4-related and was located in the submucosal layer extending to the subserosal region...
July 21, 2016: Modern Rheumatology
Erika Nuka, Susumu Tomono, Akari Ishisaka, Yoji Kato, Noriyuki Miyoshi, Yoshichika Kawai
Lipid peroxidation products react with cellular molecules, such as DNA bases, to form covalent adducts, which are associated with aging and disease processes. Since lipid peroxidation is a complex process and occurs in multiple stages, there might be yet unknown reaction pathways. Here, we analyzed comprehensively 2'-deoxyguanosine (dG) adducts with oxidized arachidonic acid using liquid chromatography-tandem mass spectrometry and found the formation of 7-(2-oxo-hexyl)-etheno-dG as one of the major unidentified adducts...
October 2016: Bioscience, Biotechnology, and Biochemistry
Daniel P Killeen, Lesley Larsen, Franck E Dayan, Keith C Gordon, Nigel B Perry, John W van Klink
Four trimethylated acylphloroglucinols (5-8) have been isolated from ma̅nuka (Leptospermum scoparium) foliage. Apart from myrigalone A (8), which has previously been isolated from European bog myrtle (Myrica gale), these compounds have not been characterized before. The nortriketones are structurally similar to the bioactive tetramethylated β-triketones from ma̅nuka, but have one less ring methyl group. Two oxidized trimethylated compounds, 9 and 10, were also isolated, but these are likely isolation artifacts...
March 25, 2016: Journal of Natural Products
Chinatsu Shimafuji, Megumi Noguchi, Mami Nishie, Jun-Ichi Nagao, Kouki Shioya, Takeshi Zendo, Jiro Nakayama, Kenji Sonomoto
Lantibiotics are antibacterial peptides containing unique thioether cross-links termed lanthionine and methyllanthionine. NukM, the modifying enzyme of nukacin ISK-1, which is produced by Staphylococcus warneri ISK-1, catalyzes the dehydration of specific Ser/Thr residues in a precursor peptide, followed by conjugative addition of intramolecular Cys to dehydrated residues to generate a cyclic structure. By contrast, the precursor peptide of nisin is modified by 2 enzymes, NisB and NisC, which mediate dehydration and cyclization, respectively...
December 2015: Journal of Bioscience and Bioengineering
Alex Mitchell, Hsin-Yu Chang, Louise Daugherty, Matthew Fraser, Sarah Hunter, Rodrigo Lopez, Craig McAnulla, Conor McMenamin, Gift Nuka, Sebastien Pesseat, Amaia Sangrador-Vegas, Maxim Scheremetjew, Claudia Rato, Siew-Yit Yong, Alex Bateman, Marco Punta, Teresa K Attwood, Christian J A Sigrist, Nicole Redaschi, Catherine Rivoire, Ioannis Xenarios, Daniel Kahn, Dominique Guyot, Peer Bork, Ivica Letunic, Julian Gough, Matt Oates, Daniel Haft, Hongzhan Huang, Darren A Natale, Cathy H Wu, Christine Orengo, Ian Sillitoe, Huaiyu Mi, Paul D Thomas, Robert D Finn
The InterPro database ( is a freely available resource that can be used to classify sequences into protein families and to predict the presence of important domains and sites. Central to the InterPro database are predictive models, known as signatures, from a range of different protein family databases that have different biological focuses and use different methodological approaches to classify protein families and domains. InterPro integrates these signatures, capitalizing on the respective strengths of the individual databases, to produce a powerful protein classification resource...
January 2015: Nucleic Acids Research
Philip Jones, David Binns, Hsin-Yu Chang, Matthew Fraser, Weizhong Li, Craig McAnulla, Hamish McWilliam, John Maslen, Alex Mitchell, Gift Nuka, Sebastien Pesseat, Antony F Quinn, Amaia Sangrador-Vegas, Maxim Scheremetjew, Siew-Yit Yong, Rodrigo Lopez, Sarah Hunter
Robust large-scale sequence analysis is a major challenge in modern genomic science, where biologists are frequently trying to characterize many millions of sequences. Here, we describe a new Java-based architecture for the widely used protein function prediction software package InterProScan. Developments include improvements and additions to the outputs of the software and the complete reimplementation of the software framework, resulting in a flexible and stable system that is able to use both multiprocessor machines and/or conventional clusters to achieve scalable distributed data analysis...
May 1, 2014: Bioinformatics
Sarah Hunter, Matthew Corbett, Hubert Denise, Matthew Fraser, Alejandra Gonzalez-Beltran, Christopher Hunter, Philip Jones, Rasko Leinonen, Craig McAnulla, Eamonn Maguire, John Maslen, Alex Mitchell, Gift Nuka, Arnaud Oisel, Sebastien Pesseat, Rajesh Radhakrishnan, Philippe Rocca-Serra, Maxim Scheremetjew, Peter Sterk, Daniel Vaughan, Guy Cochrane, Dawn Field, Susanna-Assunta Sansone
Metagenomics is a relatively recently established but rapidly expanding field that uses high-throughput next-generation sequencing technologies to characterize the microbial communities inhabiting different ecosystems (including oceans, lakes, soil, tundra, plants and body sites). Metagenomics brings with it a number of challenges, including the management, analysis, storage and sharing of data. In response to these challenges, we have developed a new metagenomics resource ( that allows users to easily submit raw nucleotide reads for functional and taxonomic analysis by a state-of-the-art pipeline, and have them automatically stored (together with descriptive, standards-compliant metadata) in the European Nucleotide Archive...
January 2014: Nucleic Acids Research
Katherine Gottlieb
Southcentral Foundation's Nuka System of Care, based in Anchorage, Alaska, is a result of a customer-driven overhaul of what was previously a bureaucratic system centrally controlled by the Indian Health Service. Alaska Native people are in control as the "customer-owners" of this health care system. The vision and mission focus on physical, mental, emotional, and spiritual wellness and working together as a Native Community. Coupled with operational principles based on relationships, core concepts and key points, this framework has fostered an environment for creativity, innovation and continuous quality improvement...
2013: International Journal of Circumpolar Health
Gustavo A Valenzuela, Nathan A Jacobson, Derik J Geist, Richard G Valenzuela, Robert A Teitge
Accurate implant positioning and restoration of lower limb alignment are major requirements for successful long-term results in unicompartmental knee arthroplasty (UKA). Alignment accuracy was compared between navigated-UKA (nUKA) and conventional-UKA (cUKA) groups using a retrospective matched case-control study (n=129, 58 nUKA, 71 cUKA). Mechanical axis (MA), hip-knee-ankle angle (HKA°), coronal implant alignment, and tibial implant posterior slope were measured. No statistically significant difference was observed when comparing MA, HKA° or coronal implant alignment (p>0...
March 2013: Journal of Arthroplasty
Mami Nishie, Makoto Sasaki, Jun-ichi Nagao, Takeshi Zendo, Jiro Nakayama, Kenji Sonomoto
Lantibiotics are ribosomally synthesized and post-translationally modified peptide antibiotics that contain unusual amino acids such as dehydro and lanthionine residues. Nukacin ISK-1 is a class II lantibiotic, whose precursor peptide (NukA) is modified by NukM to form modified NukA. ATP-binding cassette (ABC) transporter NukT is predicted to cleave off the N-terminal leader peptide of modified NukA and secrete the mature peptide. Multiple sequence alignments revealed that NukT has an N-terminal peptidase domain (PEP) and a C-terminal ATP binding domain (ABD)...
April 1, 2011: Journal of Biological Chemistry
Jun-Ichi Nagao, Kouki Shioya, Yoshitaka Harada, Ken-Ichi Okuda, Takeshi Zendo, Jiro Nakayama, Kenji Sonomoto
Alteration of protein structure and function by introducing unusual amino acids has great potential to develop new biological tool and to produce novel therapeutic agents. Lantibiotics produced by Gram-positive bacteria are ribosomally synthesized and post-translationally modified antimicrobial peptides. The modification enzyme involved in lantibiotic biosynthesis can catalyze the formation of unusual amino acids in the nascent lantibiotic prepeptide. Here, a novel methodology on the lantibiotic nukacin ISK-1 is described for engineering unusual amino acid residues into hexa-histidine-tagged (His-tagged) prepeptide NukA by the modification enzyme NukM in Escherichia coli...
2011: Methods in Molecular Biology
Hilana Ceotto, Helge Holo, Karlla Fernanda Silva da Costa, Janaína dos Santos Nascimento, Zhian Salehian, Ingolf F Nes, Maria do Carmo de Freire Bastos
Nukacin 3299 (formerly designated simulancin 3299), produced by a Staphylococcus simulans strain involved in bovine mastitis in Brazil, is the first peptide bacteriocin described in this staphylococcal species. With the intent to elucidate some aspects of its biology, nukacin 3299 was purified and characterized. The mass of the purified bacteriocin was shown to be 2957.3 Da, and the peptide N-terminal amino acids (KKKSGVI) were identified by Edman degradation. The nukacin 3299 structural gene, nukA, was detected by PCR and DNA sequencing, showing that this bacteriocin is identical to nukacin ISK-1, a 27-amino acid type-A (II) lantibiotic produced by Staphylococcus warneri ISK-1, isolated from a "nukadoko", in Japan...
November 20, 2010: Veterinary Microbiology
Takashi Furukawa, Kazuo Ito, Satoshi Nuka, Junichi Hashimoto, Hiroshi Takei, Masatoshi Takahara, Toshihiko Ogino, Marian F Young, Tamayuki Shinomura
STUDY DESIGN: A study of the histologic changes of the intervertebral discs (IVDs) in biglycan (Bgn)-deficient mice. OBJECTIVE: In this study, we investigate whether the absence of Bgn accelerates the degenerative process in mouse intervertebral disc (IVD). SUMMARY OF BACKGROUND DATA: Proteoglycans and collagen fibrils are major components in the extracellular matrix (ECM) composition of IVD. The ECM of IVD contains several members of the small leucine repeat proteoglycans (SLRPs) family...
December 1, 2009: Spine
S Nuka, W Zhou, S P Henry, C M Gendron, J B Schultz, T Shinomura, J Johnson, Y Wang, D R Keene, R Ramírez-Solis, R R Behringer, M F Young, M Höök
OBJECTIVE: To characterize the in vivo role epiphycan (Epn) has in cartilage development and/or maintenance. METHODS: Epn-deficient mice were generated by disrupting the Epn gene in mouse embryonic stem cells. Epn/biglycan (Bgn) double-deficient mice were produced by crossing Epn-deficient mice with Bgn-deficient mice. Whole knee joint histological sections were stained using van Gieson or Fast green/Safranin-O to analyze collagen or proteoglycan content, respectively...
January 2010: Osteoarthritis and Cartilage
Kouki Shioya, Yoshitaka Harada, Jun-ichi Nagao, Jiro Nakayama, Kenji Sonomoto
The lantibiotic nukacin ISK-1 is an antimicrobial peptide containing unusual amino acids such as lanthionine and dehydrobutyrine. The nukacin ISK-1 prepeptide (NukA) undergoes posttranslational modifications, such as the dehydration and cyclization reactions required to form the unusual amino acids by the modification enzyme NukM. We have previously constructed a system for the introduction of unusual amino acids into NukA by coexpression of NukM in Escherichia coli. Using this system, we describe the substrate specificity of NukM by the coexpression of a series of NukA mutants...
April 2010: Applied Microbiology and Biotechnology
Mami Nishie, Kouki Shioya, Jun-Ichi Nagao, Hiroyuki Jikuya, Kenji Sonomoto
NukT, a possible ABC transporter maturation and secretion (AMS) protein, may contribute to the cleavage of the leader peptide of NukA, which is the prepeptide of the lantibiotic nukacin ISK-1, and to nukacin ISK-1 transport. In this study, we reconstituted in vitro peptidase activity of the full-length NukT overexpressed in inside-out membrane vesicles of Staphylococcus carnosus TM300. We found that the presence of unusual amino acids in NukA is required for leader peptide cleavage. Furthermore, NukT peptidase activity was inhibited by phenylmethylsulfonyl fluoride, a serine/cysteine protease inhibitor; this finding strongly suggests that NukT, like other AMS proteins, is a cysteine protease...
December 2009: Journal of Bioscience and Bioengineering
Jun-Ichi Nagao, Yoshiko Morinaga, Mohammad R Islam, Sikder M Asaduzzaman, Yuji Aso, Jiro Nakayama, Kenji Sonomoto
The prepeptide NukA of the lantibiotic nukacin ISK-1 consists of an N-terminal leader peptide followed by a propeptide moiety that undergoes post-translational modifications, that is, formation of unusual amino acids by NukM, cleavage of the leader peptide and transport by NukT to yield a mature peptide. To identify the region and conformation required for the maturation of prepeptide, we expressed a series of NukA mutants, mutants with the N-terminus-truncated leader peptide and site-directed mutants with conserved residues in the leader peptide of type A(II) lantibiotics, which were evaluated on the basis of the production of nukacin ISK-1...
August 2009: Peptides
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