94 research outputs found

    Immature and Maturation-Resistant Human Dendritic Cells Generated from Bone Marrow Require Two Stimulations to Induce T Cell Anergy In Vitro

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    Immature dendritic cells (DC) represent potential clinical tools for tolerogenic cellular immunotherapy in both transplantation and autoimmunity. A major drawback in vivo is their potential to mature during infections or inflammation, which would convert their tolerogenicity into immunogenicity. The generation of immature DC from human bone marrow (BM) by low doses of GM-CSF (lowGM) in the absence of IL-4 under GMP conditions create DC resistant to maturation, detected by surface marker expression and primary stimulation by allogeneic T cells. This resistence could not be observed for BM-derived DC generated with high doses of GM-CSF plus IL-4 (highGM/4), although both DC types induced primary allogeneic T cell anergy in vitro. The estabishment of the anergic state requires two subsequent stimulations by immature DC. Anergy induction was more profound with lowGM-DC due to their maturation resistance. Together, we show the generation of immature, maturation-resistant lowGM-DC for potential clinical use in transplant rejection and propose a two-step-model of T cell anergy induction by immature DC

    Involvement of the Cytokine MIF in the Snail Host Immune Response to the Parasite Schistosoma mansoni

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    We have identified and characterized a Macrophage Migration Inhibitory Factor (MIF) family member in the Lophotrochozoan invertebrate, Biomphalaria glabrata, the snail intermediate host of the human blood fluke Schistosoma mansoni. In mammals, MIF is a widely expressed pleiotropic cytokine with potent pro-inflammatory properties that controls cell functions such as gene expression, proliferation or apoptosis. Here we show that the MIF protein from B. glabrata (BgMIF) is expressed in circulating immune defense cells (hemocytes) of the snail as well as in the B. glabrata embryonic (Bge) cell line that has hemocyte-like features. Recombinant BgMIF (rBgMIF) induced cell proliferation and inhibited NO-dependent p53-mediated apoptosis in Bge cells. Moreover, knock-down of BgMIF expression in Bge cells interfered with the in vitro encapsulation of S. mansoni sporocysts. Furthermore, the in vivo knock-down of BgMIF prevented the changes in circulating hemocyte populations that occur in response to an infection by S. mansoni miracidia and led to a significant increase in the parasite burden of the snails. These results provide the first functional evidence that a MIF ortholog is involved in an invertebrate immune response towards a parasitic infection and highlight the importance of cytokines in invertebrate-parasite interactions

    FACT, the Bur Kinase Pathway, and the Histone Co-Repressor HirC Have Overlapping Nucleosome-Related Roles in Yeast Transcription Elongation

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    Gene transcription is constrained by the nucleosomal nature of chromosomal DNA. This nucleosomal barrier is modulated by FACT, a conserved histone-binding heterodimer. FACT mediates transcription-linked nucleosome disassembly and also nucleosome reassembly in the wake of the RNA polymerase II transcription complex, and in this way maintains the repression of ‘cryptic’ promoters found within some genes. Here we focus on a novel mutant version of the yeast FACT subunit Spt16 that supplies essential Spt16 activities but impairs transcription-linked nucleosome reassembly in dominant fashion. This Spt16 mutant protein also has genetic effects that are recessive, which we used to show that certain Spt16 activities collaborate with histone acetylation and the activities of a Bur-kinase/Spt4–Spt5/Paf1C pathway that facilitate transcription elongation. These collaborating activities were opposed by the actions of Rpd3S, a histone deacetylase that restores a repressive chromatin environment in a transcription-linked manner. Spt16 activity paralleling that of HirC, a co-repressor of histone gene expression, was also found to be opposed by Rpd3S. Our findings suggest that Spt16, the Bur/Spt4–Spt5/Paf1C pathway, and normal histone abundance and/or stoichiometry, in mutually cooperative fashion, facilitate nucleosome disassembly during transcription elongation. The recessive nature of these effects of the mutant Spt16 protein on transcription-linked nucleosome disassembly, contrasted to its dominant negative effect on transcription-linked nucleosome reassembly, indicate that mutant FACT harbouring the mutant Spt16 protein competes poorly with normal FACT at the stage of transcription-linked nucleosome disassembly, but effectively with normal FACT for transcription-linked nucleosome reassembly. This functional difference is consistent with the idea that FACT association with the transcription elongation complex depends on nucleosome disassembly, and that the same FACT molecule that associates with an elongation complex through nucleosome disassembly is retained for reassembly of the same nucleosome

    Schizophrenia and reelin: a model based on prenatal stress to study epigenetics, brain development and behavior

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    TEKNIK PENYARINGAN DATA MODEL PERMUKAAN DIGITAL MENJADI DATA MODEL TERAIN DIGITAL PADA AREA VEGETASI DAN AREA PEMUKIMAN

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    Aerial photogrametry is one of methods to produce digital elevation model data. Nowaday, almost aerial photogrametry use image matching technique to make digital elevation model data. The main problem that is arise on processing image matching is that the product result that is still on data digital surface model (MPD) format, in fact, mostly of map users use digital terrain model data (MTD). To produce digital terrain model data, filtering the digital surface model data from aerial photo is needed to do by using slope based filtering mode. This slope based filtering mode is used to filter digital surface model of Kentungan area to become digital terrain model data. The first step is to choose two tipes of area digital surface model data area of Kentungan will be filtered, namely vegetation and urban areas. Both digital surface model data are exported to xyz data format, so the data can be processed in Saga gis 2.1.0 software using slope based filtering method. This slope based filtering method remove height point data from digital surface model data that don�t represent technique terrain height point data. The result of research shows that digital terrain data from slope based filtering technique result on urban areas data is less accurate compared to vegetation areas on Kentunga. It is indicated by the presence of a high point after the terrain is filtered repeatedly. Analysis of the results is also performed visually on Global Mapper 13.2 software 3- dimensional model on Saga gis software 2.1.0. Filtering data digital surface model is also analyzed numerically by calculating statistics such as the highest point, the point of lows and the high point of the average data before and after filtered. The data obtained by the reduction of vegetation area represents a high point of 10 558 meters of residential areas and the reduction obtained high point of 7,847 meters. Key word : digital surface model, digital terrain model, slope based filtering

    Bentuk Pertanggungjawaban Atas Kerugian Yang Disebabkan Oleh Robot Trading Forex Dengan Sistem Mirror Trading Dan Copy Trading

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    Agnes Natalia Desilva, Hukum Ekonomi Bisnis, Fakultas Hukum Universitas Brawijaya, April 2022, Bentuk Pertanggungjawaban Atas Kerugian Yang Disebabkan Oleh Robot Trading Forex Dengan Sistem Mirror Trading Dan Copy Trading, Dr. Sihabudin, S.H., M.H., Ranitya Ganindha, S.H., M.H. Pada Skripsi Ini, Penulis Mengangkat Permasalahan Mengenai Bentuk Pertanggungjawaban Atas Perbuatan Robot Trading Forex Dengan Sistem Mirror Trading Dan Copy Trading Di Indonesia. Tema Tersebut Dilatarbelakangi Oleh Maraknya Penggunaan Robot Trading Forex Oleh Masyarakat Indonesia, Yang Kemudian Diketahui Bahwa Robot Trading Forex Tersebut Menggunakan Sistem Mirror Trading Dan Copy Trading. Permasalahan Yang Kemudian Timbul Adalah Terkait Pertanggungjawaban Atas Perbuatan Robot Trading Apabila Menimbulkan Kerugian, Yang Oleh Penulis Dilakukan Analisis Terkait Bentuk Pertanggungjawaban Apa Yang Tepat, Serta Siapa Yang Akan Bertanggung Jawab. Selain Itu Diketahui Juga Bahwa Maraknya Penggunaan Robot Trading Tersebut Tidak Disertai Dengan Aturan Yang Secara Spesifik Mengatur Mengenai Robot Trading. Hal Ini Kemudian Menimbulkan Permasalahan Lain Yakni Robot Trading Yang Dinyatakan Ilegal, Karena Tidak Adanya Izin Yang Dikeluarkan Oleh Bappebti. Sehingga Perlu Adanya Aturan Yang Mengatur Robot Trading Secara Spesifik. Berdasarkan Hal Tersebut, Skripsi Ini Kemudian Mengangkat Rumusan Masalah: (1) Bagaimana Bentuk Pertanggung Jawaban Atas Perbuatan Robot Trading Forex Dengan Sistem Mirror Trading Dan Copy Trading? (2) Bagaimana Pengaturan Robot Trading Forex Dengan Sistem Mirror Trading Dan Copy Trading Di Indonesia? Penulisan Skripsi Ini Menggunakan Menggunakan Metode Yuridis Normatif Dengan Metode Pendekatan Perundang-Undangan (Statute Approach) Dan Metode Pendekatan Perbandingan (Comparative Approach). Bahan Hukum Primer, Sekunder Dan Tersier Yang Diperoleh Penulis Akan Dianalisis Dengan Menggunakan Metode Penafsiran Gramatikal, Penafsiran Sistematis Dan Penafsiran Komparatif. Kemudian Dari Hasil Penelitian Dengan Menggunakan Metode-Metode Diatas, Penulis Memperoleh Jawaban Atas Permasalahan Yang Ada, Bahwa Bentuk Pertanggungjawaban Atas Perbuatan Robot Trading Forex Dengan Sistem Mirror Trading Dan Copy Trading Adalah Pertanggungjawaban Pengganti (Vicarious Liability), Karena Robot Trading Adalah Objek Hukum Berupa Benda Yang Digunakan Sebagai Alat Dalam Perdagangan Berjangka Komoditi Serta Sebagai Pekerja Yang Melakukan Pekerjaan Atas Perintah Dan Kemauan Dari Robot Trading Provider. Sehingga Apabila Akibat Perbuatannya Robot Trading Forex Menimbulkan Kerugian, Maka Robot Trading Provider Yang Harus Bertanggung Jawab. Selain Itu Di Indonesia Belum Ada Pengaturan Mengenai Robot Trading Dengan Sistem Mirror Trading Dan Copy Trading. Namun Sebagai Sistem Elektronik, Robot Trading Diatur Oleh Beberapa Peraturan Perundang-Undangan Mengenai Sistem Elektronik. Akan Tetapi Tetap Diperlukan Aturan Yang Secara Khusus Dibentuk Untuk Mengatur Secara Spesifik Mengenai Robot Trading, Yang Kemudian Dapat Diterapkan Juga Pada Robot Trading Forex Dengan Sistem Mirror Trading Dan Copy Trading Yang Sedang Marak Di Indonesia

    Impedance Imaging of Chemical and Biochemical Systems

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    The non-linearity of RAF-MEK signaling in dendritic cells

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