33 research outputs found

    Persepsi Masyarakat terhadap Rencana Pemekaran Kabupaten Bone Selatan

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    This study aims to determine how the public perception of late kabupateb Bone pemekar south. In general, community leaders know the plan establishmen-Tukan Bone District; Community leaders is very great hopes to its efforts to establish the district of Bone South, due to the formation of new districts in the future, will create employment opportunities were great, they also expect the government to get closer to the people, pay more attention to their fate, the service can be enjoyed with easy, free of corruption, equitable growth, the potential of the area can be managed properly and a decent future for their offspring would be wide open; High public approval rate, can not be separated from the ladder-pan / understanding of the benefits of a granting autonomy to the region.Keywords: South Bone Splitting District, Autonomous Rights, Local GovernmentPenelitian ini bertujuan untuk mengetahui bagaimana persepsi masyarakat terhadap pemekaran kabupateb Bone selatan. Pada umumnya tokoh masyarakat mengetahui rencana pembentukan Kabupaten Bone; Tokoh masyarakat sangat menaruh harapan besar terhadap upaya pembentukan daerah Kabupaten Bone Selatan, karena dengan terbentuknya kabupaten baru ini kelak, akan menciptakan peluang lapangan pekerjaan yang besar, mereka juga berharap agar pemerintah lebih mendekatkan diri kepada masyarakat, lebih memperhatikan nasib mereka, pelayanan dapat dinikmati dengan mudah, bebas KKN, pembangunan yang merata, potensi daerah dapat dikelola dengan baik dan masa depan yang layak bagi keturunan mereka akan terbuka lebar; Tingkat persetujuan masyarakat yang tinggi, tidak terlepas dari tanggapan/pemahaman akan manfaat sebuah pemberian hak otonomi kepada sebuah daerah

    The gut bacterium and pathobiont Bacteroides vulgatus activates NF-ÎșB in a human gut epithelial cell line in a strain and growth phase dependent manner

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    The gut microbiota is increasingly implicated in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC) although the identity of the bacteria that underpin these diseases has remained elusive. The pathobiont Bacteroides vulgatus has been associated with both diseases although relatively little is known about how its growth and functional activity might drive the host inflammatory response. We identified an ATP Binding Cassette (ABC) export system and lipoprotein in B. vulgatus ATCC 8482 and B. vulgatus PC510 that displayed significant sequence similarity to an NF-ÎșB immunomodulatory regulon previously identified on a CD-derived metagenomic fosmid clone. Interestingly, the ABC export system was specifically enriched in CD subjects suggesting that it may be important for colonization and persistence in the CD gut environment. Both B. vulgatus ATCC 8482 and PC510 activated NF-ÎșB in a strain and growth phase specific manner in a HT-29/kb-seap-25 enterocyte like cell line. B. vulgatus ATCC 8482 also activated NF-ÎșB in a Caco-2-NF-ÎșBluc enterocyte like and an LS174T-NF-ÎșBluc goblet cell like cell lines, and induced NF-ÎșB-p65 subunit nuclear translocation and IL-6, IL-8, CXCL-10 and MCP-1 gene expression. Despite this, NF-ÎșB activation was not coincident with maximal expression of the ABC exporter or lipoprotein in B. vulgatus PC510 suggesting that the regulon may be necessary but not sufficient for the immunomodulatory effects

    Identification and characterization of Cardiac Glycosides as senolytic compounds

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    Compounds with specific cytotoxic activity in senescent cells, or senolytics, support the causal involvement of senescence in aging and offer therapeutic interventions. Here we report the identification of Cardiac Glycosides (CGs) as a family of compounds with senolytic activity. CGs, by targeting the Na+/K+ATPase pump, cause a disbalanced electrochemical gradient within the cell causing depolarization and acidification. Senescent cells present a slightly depolarized plasma membrane and higher concentrations of H+, making them more susceptible to the action of CGs. These vulnerabilities can be exploited for therapeutic purposes as evidenced by the in vivo eradication of tumors xenografted in mice after treatment with the combination of a senogenic and a senolytic drug. The senolytic effect of CGs is also effective in the elimination of senescence-induced lung fibrosis. This experimental approach allows the identification of compounds with senolytic activity that could potentially be used to develop effective treatments against age-related diseases.We thank Matthias Drosten, Alejo Efeyan and Sean Morrison for plasmids. F.T-M. is a postdoctoral fellow from CONACYT (cvu 268632); P.P. is a predoctoral fellow from Xunta de Galicia; M.C. is a "Miguel Servet II" investigator (CPII16/00015). P.P.-R. receives support from a program by the Deputacion de Coruna (BINV-CS/2019). Work in the laboratory of M.C. is funded by grant RTI2018-095818-B-100 (MCIU/AEI/FEDER, UE). P.J.F.-M. is funded by the IMDEA Food Institute, the Ramon Areces Foundation, (CIVP18A3891), and a Ramon y Cajal Award (MICINN) (RYC-2017-22335). M.P.I. is funded by Talento Modalidad-1 Program Grant, Madrid Regional Government (#2018-T1/BIO-11262). F.P. was funded by a Long Term EMBO Fellowship (ALTF-358-2017) and F.H-G. was funded by the PhD4MD Programme of the IRB, Hospital Clinic and IDIBAPS. Work in the laboratory of M.S. was funded by the IRB and by grants from the Spanish Ministry of Economy co-funded by the European Regional Development Fund (ERDF) (SAF2013-48256-R), the European Research Council (ERC-2014-AdG/669622), and "laCaixa" Foundation.S

    The disruption of GDP-fucose de novo biosynthesis suggests the presence of a novel fucose-containing glycoconjugate in <i>Plasmodium</i> asexual blood stages

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    Glycosylation is an important posttranslational protein modification in all eukaryotes. Besides glycosylphosphatidylinositol (GPI) anchors and N-glycosylation, O-fucosylation has been recently reported in key sporozoite proteins of the malaria parasite. Previous analyses showed the presence of GDP-fucose (GDP-Fuc), the precursor for all fucosylation reactions, in the blood stages of Plasmodium falciparum. The GDP-Fuc de novo pathway, which requires the action of GDP-mannose 4,6-dehydratase (GMD) and GDP-L-fucose synthase (FS), is conserved in the parasite genome, but the importance of fucose metabolism for the parasite is unknown. To functionally characterize the pathway we generated a PfGMD mutant and analyzed its phenotype. Although the labelling by the fucose-binding Ulex europaeus agglutinin I (UEA-I) was completely abrogated, GDP-Fuc was still detected in the mutant. This unexpected result suggests the presence of an alternative mechanism for maintaining GDP-Fuc in the parasite. Furthermore, PfGMD null mutant exhibited normal growth and invasion rates, revealing that the GDP-Fuc de novo metabolic pathway is not essential for the development in culture of the malaria parasite during the asexual blood stages. Nonetheless, the function of this metabolic route and the GDP-Fuc pool that is generated during this stage may be important for gametocytogenesis and sporogonic development in the mosquito

    Serine-Rich Repeat Protein adhesins from Lactobacillus reuteri display strain specific glycosylation profiles

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    Lactobacillus reuteri is a gut symbiont inhabiting the gastrointestinal tract of numerous vertebrates. The surface-exposed Serine-Rich Repeat Protein (SRRP) is a major adhesin in Gram-positive bacteria. Using lectin and sugar nucleotide profiling of wild-type or L. reuteri isogenic mutants, MALDI-ToF-MS, LC-MS and GC-MS analyses of SRRPs, we showed that L. reuteri strains 100-23C (from rodent) and ATCC 53608 (from pig) can perform protein O-glycosylation and modify SRRP100-23 and SRRP53608 with Hex-Glc-GlcNAc and di-GlcNAc moieties, respectively. Furthermore, in vivo glycoengineering in E. coli led to glycosylation of SRRP53608 variants with α-GlcNAc and GlcNAcÎČ(1→6)GlcNAcα moieties. The glycosyltransferases involved in the modification of these adhesins were identified within the SecA2/Y2 accessory secretion system and their sugar nucleotide preference determined by saturation transfer difference NMR spectroscopy and differential scanning fluorimetry. Together, these findings provide novel insights into the cellular O-protein glycosylation pathways of gut commensal bacteria and potential routes for glycoengineering applications

    Linking full-text grey literature to underlying research and post-publication data: An Enhanced Publications Project 2011-2012

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    1. The Project This project seeks to circumvent the data vs. documents camp in the grey literature community by way of a middle ground provided through enhanced publications. Enhanced publications allow for a fuller understanding of the process in which data and information are used and applied in the generation of knowledge. The enhanced publication of grey literature precludes the idea of a random selection of data and information, and instead focuses on the human intervention in data-rich environments. The definition of an enhanced publication is borrowed from the DRIVER-II project, “a publication that is enhanced with three categories of information: research data, extra materials, and post-publication data”. Enhanced publications combine textual resources i.e. documents intended to be read by human beings, which contain an interpretation or analysis of primary data. Enhanced publications inherently contribute to the review process of grey literature as well as the replication of research and improved visibility of research results in the scholarly communication chain. 2. Design of the Questionnaire and Author Survey The population of the survey was selected from among the 286 authors and co-authors in the International Conference Series on Grey Literature. It was decided that only first authors would receive the questionnaire, which narrowed the potential population of the survey to 162 authors of which only 95 were actually sent the online questionnaire. The reason the other 67 first authors were not included in the final survey population was due to a number of factors such as no current email address, retired, deceased, etc. The 95 authors were sent a personalized email with a standardized text inviting them to participate in the survey by completing the online questionnaire. The survey was carried out using the freeware ‘Survey Monkey’ and the questionnaire contained 10 items, three of which were open-ended. Subheadings were also inserted in the questionnaire set off by quotation marks. These subheadings preceded each odd numbered question and were deemed relevant in achieving informed responses. The final results are based on the response of 50 of the 95 survey recipients, which amounts to roughly a 53% response rate
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