4,130 research outputs found
System-level investigation into the regulatory mechanism of the calcineurin/NFAT signaling pathway
No full textCalcineum/nuclear factor of the activated T cell (CaN/NFAT) signaling pathway plays crucial roles in the development of cardiac hypertrophy, Down's syndrome, and autoimmune diseases in response to pathological stimuli. The aim of the present study is to get a system-level understanding on the regulatory mechanism of CaN/NFAT signaling pathway in consideration of the controversial roles of myocyte-enriched calcineurin interacting protein1 (MCIP1) for varying stress stimuli. To this end, we have developed an experimentally validated mathematical model and carried out computer simulations as well as cell-based experiments. Quantitative overexpression and knock-down experiments in C2C12 myoblasts have revealed that MCIP1 functions only as a calcineurin inhibitor. We have also observed a biphasic response of the NFAT activity with increasing stimuli of isoproterenol. Through extensive in silico simulations, we have discovered that the NFAT activity is primarily modulated by ERK5 and MCIP1 under mild isoproterenol stimuli whereas it is mainly modulated by atrogin1 (muscle atrophy F-box protein) under strong isoproterenol stimuli. This study shows that a system-level analysis may help understanding CaN/NFAT signaling-associated disease. (C) 2008 Elsevier Inc. All rights reserved
The SSC of the Generalised Jahangir’s Graph Jm,k and its Algebraic Characterizations
No full textIn this article, we present important combinatorial and algebraicproperties of spanning simplicial complex (SSC) of the generalised Jahangir’sgraph Jm,k. We describe the relation to find f−vectors associatedto Δs(Jm,k) and determine the Hilbert series for the SR-ring KΔs(Jm,k).In the end, we present the associated primes of the facet ideal IF(Δs(Jm,k))and the Cohen-Macaulay characterization of the SR-ring of Δs(Jm,k).AMS (MOS) Subject Classification Codes: Primary 13-P10, Secondary 13-F20, 13-C14, 13-H10.Corresponding Author: Agha KashifKey Words: Simplicial Complexes, f-vectors, Spanning Trees, Face Ring, Hilbert Series, CohenMacaulay
To <i>JM</i> on Its 75th Anniversary
No full text This article discusses how Journal of Marketing ( JM) has influenced marketing science and practice by publishing articles on substantive topics relevant to customers, managers, organizations, markets, and society. The journal's 75th anniversary coincides with the 50th anniversary of the Marketing Science Institute (MSI). Frequently, JM and MSI have collaborated to address important substantive marketing issues identified in MSI's Research Priorities. The author highlights seminal articles on brand equity; business-to-business marketing (including sales force management); connecting marketing information, metrics, and strategy; consumer behavior; innovation, new product development. and product management; marketing orientation and capabilities; and market research, methodology and services. She also draws attention to articles that have won the Sheth Foundation/ JM Award and the H. Paul Root Award. The article describes how JM‘s knowledge dissemination is amplified by powerful social network effects. Ideas in JM articles diffuse through the business community, influencing the mind-set of managers worldwide. </jats:p
Repetitive DNA is associated with centromeric domains in Trypanosoma brucei but not Trypanosoma cruzi.
No full textBACKGROUND: Trypanosomes are parasitic protozoa that diverged early from the main eukaryotic lineage. Their genomes display several unusual characteristics and, despite completion of the trypanosome genome projects, the location of centromeric DNA has not been identified. RESULTS: We report evidence on the location and nature of centromeric DNA in Trypanosoma cruzi and Trypanosoma brucei. In T. cruzi, we used telomere-associated chromosome fragmentation and found that GC-rich transcriptional 'strand-switch' domains composed predominantly of degenerate retrotranposons are a shared feature of regions that confer mitotic stability. Consistent with this, etoposide-mediated topoisomerase-II cleavage, a biochemical marker for active centromeres, is concentrated at these domains. In the 'megabase-sized' chromosomes of T. brucei, topoisomerase-II activity is also focused at single loci that encompass regions between directional gene clusters that contain transposable elements. Unlike T. cruzi, however, these loci also contain arrays of AT-rich repeats stretching over several kilobases. The sites of topoisomerase-II activity on T. brucei chromosome 1 and T. cruzi chromosome 3 are syntenic, suggesting that centromere location has been conserved for more than 200 million years. The T. brucei intermediate and minichromosomes, which lack housekeeping genes, do not exhibit site-specific accumulation of topoisomerase-II, suggesting that segregation of these atypical chromosomes might involve a centromere-independent mechanism. CONCLUSION: The localization of centromeric DNA in trypanosomes fills a major gap in our understanding of genome organization in these important human pathogens. These data are a significant step towards identifying and functionally characterizing other determinants of centromere function and provide a framework for dissecting the mechanisms of chromosome segregation
JM-20, a Benzodiazepine-Dihydropyridine Hybrid Molecule, Inhibits the Formation of Alpha-Synuclein-Aggregated Species
No full text\ua9 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.Studies showed that JM-20, a benzodiazepine-dihydropyridine hybrid molecule, protects against rotenone and 6-hydroxydopamine neurotoxicity. However, its protective effects against cytotoxicity induced by endogenous neurotoxins involved in Parkinson’s disease (PD) pathogenesis have never been investigated. In this study, we evaluated the ability of JM-20 to inhibit alpha-synuclein (aSyn) aggregation. We also evaluated the interactions of JM-20 with aSyn by molecular docking and molecular dynamics and assessed the protective effect of JM-20 against aminochrome cytotoxicity. We demonstrated that JM-20 induced the formation of heterogeneous amyloid fibrils, which were innocuous to primary cultures of mesencephalic cells. Moreover, JM-20 reduced the average size of aSyn positive inclusions in H4 cells transfected with SynT wild-type and synphilin-1-V5, but not in HEK cells transfected with synphilin-1-GFP. In silico studies showed the interaction between JM-20 and the aSyn-binding site. Additionally, we showed that JM-20 protects SH-SY5Y cells against aminochrome cytotoxicity. These results reinforce the potential of JM-20 as a neuroprotective compound for PD and suggest aSyn as a molecular target for JM-20
Uterine transplantation: a promising surrogate to surrogacy?
No full textUterine transplantation: a promising surrogate to surrogacy?
Grynberg M1, Ayoubi JM, Bulletti C, Frydman R, Fanchin R.
Author information
Abstract
Infertility due to the inability of the uterus to carry a pregnancy ranks among the most unresolved issues in reproductive medicine. It affects millions of women worldwide who have congenital or acquired uterine affections, often requiring hysterectomy, and potentially represents a considerable fraction of the general infertile population. Patients suffering from severe uterine infertility are currently compelled to go through gestational surrogacy or adoption; both approaches, unfortunately, deprive them of the maternal experience of pregnancy and birth. Uterine transplantation represents an outstanding, yet complex, perspective to alleviating definitive uterine infertility. In the past decades, a number of scientific experiments conducted both in animals and women, focusing on uterine transplantation, have led to promising results. Collectively, these findings undoubtedly constitute a sound basis to clinically apply uterine transplantation in the near future. This paper is, however, an overview not only of the extent and limitations of accumulated scientific knowledge on uterine transplantation, but also its ethical implications, in an effort to define the actual place of such an approach among the therapeutic arsenal for alleviating infertility.
© 2011 New York Academy of Sciences
Translation and interpretation: Translation redundancy reconsidered
No full textInterpretation is an integral part of the process of translating. This article raises the question of whether interpretation fo a literary work by a translator should be guided by extratextual factors or not. The discussion is illustrated with examples taken from David Hawkes' translation of a Chinese classic, A Dream of Red Mansions. As the work of a scholar-translator, Hawkes' version is richly supplemented with disclosures concerning the characters and explanations of the cultural environment embodied in the novel. In many cases, however, this translation procedure is redundant and explanatory, enlightening the readers but at the same time robbing them of the pleasure of literary interpretation and cultural exploration. By means of this illustration of translation redundancy, the author points out that there is difference between a scholar who helps the interpretation fo a work and a translator who presents a work close to its original version. It is particularly important to pay attention tot his difference in literary translations in a cross-cultural situation involving two enormously different cultures.Language & LinguisticsA&HCI0ARTICLE1,SI115-12
INTERNATIONAL FINANCIAL REPORTING STANDARDS (IFRS), BAIK BAGI USAHA MIKRO KECIL MENENGAH? (Studi Kasus: UMKM JM KERIPIK)
No full textABSTRAKUndang-undang nomor 20 tahun 2008 tentang Usaha Makro Kecil Menengah (UMKM), usaha kecil adalah usaha ekonomi produktif yang berdiri sendiri, yang dilakukan oleh orang perseorangan atau badan usaha yang bukan merupakan anak perusahaan atau bukan cabang perusahaan yang memiliki, dikuasai atau menjadi bagian baik langsung maupun tidak langsung dari usaha menengah atau usaha besar yang memenuhi kriteria. JM Keripik merupakan salah salah UMKM yang bergelut dibidang produksi dan penjualan. IFRS merupakan seperangkat standard yang dikeluarkan oleh Dewan Standard Akuntansi Internasional (IASB). IFRS berguna untuk menyusun laporan keuangan yang dapat diterima di dunia Global.Penulistertarik untukmengetahuipencatatankeuanganJM Keripik dan apakah perlu merekomendasikan IFRS pada UMKM JM Keripik. Metode penelitian yang digunakaan penulis adalah kualitatif yaitu observasi dan wawancara. Dari hasil penelitian banyak terdapat pencatatan-pencatatan yang kurang terperinci, UMKM JM Keripik hanya memilki empat macam pencatatan yaitu pencatatan mengenai: 1.Stock barang, 2.Supliyer, 3.Costumer dan 4.Stock toko, pencatatan ini hanya dapat dimengerti oleh pemilik JM Keripik. Sebaiknya pemilik UMKM JM Keripik mengganti laporan keuangan yang sederhana ke laporan keuangan yang semestinya dan yang berbasis IFRS karena IFRS membawa dampak positif bagi UMKM dan merupakan standar akuntansi keuangan yang digunakan dunia global. Kata Kunci : UMKM, IFRS, JM Keripik ABSTRACT Act number 20 of 2008 concerning the Macro Small and Medium Enterprises, small businesses are productive economic activities that stand alone, carried out by an individual or business entity that is not a subsidiary or not a branch of the company that owns, controlled or become part either directly or indirectly from medium or large businesses that meet the criteria. JM Keripik which deals in the field of production and sales. IFRS is a set of standards issued by the International Accounting Standards Board (IASB). IFRS is useful for preparing financial statements that is acceptable in the global world. Authors interested in knowing the financial records of JM Keripik and whether to recommend IFRS on JM Keripik. The research method is qualitative author of observation and interviews. From the research there are many registries are less detailed, JM Keripik has only four kinds of recording is recording about: 1.Stock goods, 2.Supliyer, 3.Costumer and 4.Stock shop, registration can only be understood by the owner of JM Keripik. JM Keripik owners should replace the simple financial reports to the appropriate financial statements and IFRS-based IFRS for Macro Small and Medium Enterprises had a positive impact and a financial accounting standards global world. Keywords : UMKM, IFRS, JM Keripi
Gridlock: chaos and confusion in our prisons
No full textBehind the headlines and political posturing, the prison system is in crisis, with inhumane conditions and overcrowding making a mockery of justice, argues Peter JM Wayne, who has spent over 20 years inside. Copyright (c) 2008 The Author. Journal compilation (c) 2008 ippr.
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