614 research outputs found
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“A Bridge Between Us”: Literature in the Ukrainian-Crimean Tatar Encounter
At a time of geopolitical instability in the Black Sea region, the question of the solidarity between two ethnically, religiously, and linguistically divergent peoples - Ukrainians and Crimean Tatars - will influence the extent to which Crimea remains a global flashpoint for the foreseeable future. Despite its significance, however, this solidary relationship has been either overlooked as a discrete object of enquiry or dismissed as a mere political "marriage of convenience" in research literature. This article seeks to delve more deeply into the dynamics of Ukrainian-Crimean Tatar relations and to direct special attention to its cultural drivers, particularly in the realm of literature. Representing the first comparative study of Ukrainian and Crimean Tatar literatures in the English language, it posits that works by such prominent figures as Lesia Ukraïnka and Şamil Alâdin have actively engaged in intricate, mutual processes of "nominal metaphorisation" since the late nineteenth century. These processes, which center on representations of experiences of victimization, help account not only for the practical and political nature of the Ukrainian-Crimean Tatar alliance, but also for its affective and empathic power
Let\u27s Get Engaged: Keys to Creating a Culture to Maximize Student Success and Enhance Retention
Was there something more we could have done? In classrooms across America, we are losing students that are unable to effectively cope with the stress of the transitional nature of college while also juggling life. Meaningful engagement can increase our students’ psychological investment in learning, their willingness and desire to learn, and their resiliency. The presenters will showcase a classroom that provides a learning environment to meet the needs of students today, where the ultimate goal is not only points, but also critical thinking and sustainable change. Participants will be empowered with strategies to foster student success through active, meaningful engagement
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Prelude to a Revolution: Reflections on Observing the 2004 Presidential Elections in Ukraine
Optimisation of selective laser melting parameters for the Ni-based superalloy IN-738 LC using Doehlert’s design
The Ni-based superalloy IN-738 LC is known to be susceptible to porosity and different types of cracking during the build-up process and, thus, challenging to manufacture using selective laser melting (SLM). Determining a feasible set of operating parameters for SLM of nickel-based superalloys involves new approach to experimental design based on the Doehlert method that assists in determining an optimal (feasible) set of operating parameters for SLM of IN-738 LC powder alloy
Histone deacetylases play distinct roles in telomeric VSG expression site silencing in African trypanosomes
African trypanosomes evade the host immune response through antigenic variation, which is achieved by periodically expressing different variant surface glycoproteins (VSGs). VSG expression is monoallelic such that only one of approximately 15 telomeric VSG expression sites (ESs) is transcribed at a time. Epigenetic regulation is involved in VSG control but our understanding of the mechanisms involved remains incomplete. Histone deacetylases are potential drug targets for diseases caused by protozoan parasites. Here, using recombinant expression we show that the essential Trypanosoma brucei deacetylases, DAC1 (class I) and DAC3 (class II) display histone deacetylase activity. Both DAC1 and DAC3 are nuclear proteins in the bloodstream stage parasite, while only DAC3 remains concentrated in the nucleus in insect-stage cells. Consistent with developmentally regulated localization, DAC1 antagonizes SIR2rp1-dependent telomeric silencing only in the bloodstream form, indicating a conserved role in the control of silent chromatin domains. In contrast, DAC3 is specifically required for silencing at VSG ES promoters in both bloodstream and insect-stage cells. We conclude that DAC1 and DAC3 play distinct roles in subtelomeric gene silencing and that DAC3 represents the first readily druggable target linked to VSG ES control in the African trypanosome
SLITHER: a web server for generating contiguous conformations of substrate molecules entering into deep active sites of proteins or migrating through channels in membrane transporters
Many proteins use a long channel to guide the substrate or ligand molecules into the well-defined active sites for catalytic reactions or for switching molecular states. In addition, substrates of membrane transporters can migrate to another side of cellular compartment by means of certain selective mechanisms. SLITHER (http://bioinfo.mc.ntu.edu.tw/slither/or http://slither.rcas.sinica.edu.tw/) is a web server that can generate contiguous conformations of a molecule along a curved tunnel inside a protein, and the binding free energy profile along the predicted channel pathway. SLITHER adopts an iterative docking scheme, which combines with a puddle-skimming procedure, i.e. repeatedly elevating the potential energies of the identified global minima, thereby determines the contiguous binding modes of substrates inside the protein. In contrast to some programs that are widely used to determine the geometric dimensions in the ion channels, SLITHER can be applied to predict whether a substrate molecule can crawl through an inner channel or a half-channel of proteins across surmountable energy barriers. Besides, SLITHER also provides the list of the pore-facing residues, which can be directly compared with many genetic diseases. Finally, the adjacent binding poses determined by SLITHER can also be used for fragment-based drug design
Identification of ‘erasers’ for lysine crotonylated histone marks using a chemical proteomics approach
Posttranslational modifications (PTMs) play a crucial role in a wide range of biological processes. Lysine crotonylation (Kcr) is a newly discovered histone PTM that is enriched at active gene promoters and potential enhancers in mammalian cell genomes. However, the cellular enzymes that regulate the addition and removal of Kcr are unknown, which has hindered further investigation of its cellular functions. Here we used a chemical proteomics approach to comprehensively profile 'eraser' enzymes that recognize a lysine-4 crotonylated histone H3 (H3K4Cr) mark. We found that Sirt1, Sirt2, and Sirt3 can catalyze the hydrolysis of lysine crotonylated histone peptides and proteins. More importantly, Sirt3 functions as a decrotonylase to regulate histone Kcr dynamics and gene transcription in living cells. This discovery not only opens opportunities for examining the physiological significance of histone Kcr, but also helps to unravel the unknown cellular mechanisms controlled by Sirt3, that have previously been considered solely as a deacetylase.published_or_final_versio
Histone deacetylases as new therapy targets for platinum-resistant epithelial ovarian cancer
Introduction: In developed countries, ovarian cancer is the fourth most common cancer in women. Due to the nonspecific symptomatology associated with the disease many patients with ovarian cancer are diagnosed late, which leads to significantly poorer prognosis. Apart from surgery and radiotherapy, a substantial number of ovarian cancer patients will undergo chemotherapy and platinum based agents are the mainstream first-line therapy for this disease. Despite the initial efficacy of these therapies, many women relapse; therefore, strategies for second-line therapies are required. Regulation of DNA transcription is crucial for tumour progression, metastasis and chemoresistance which offers potential for novel drug targets. Methods: We have reviewed the existing literature on the role of histone deacetylases, nuclear enzymes regulating gene transcription. Results and conclusion: Analysis of available data suggests that a signifant proportion of drug resistance stems from abberant gene expression, therefore HDAC inhibitors are amongst the most promising therapeutic targets for cancer treatment. Together with genetic testing, they may have a potential to serve as base for patient-adapted therapies
Histone acetylation-independent transcription stimulation by a histone chaperone
Histone chaperones are thought to be important for maintaining the physiological activity of histones; however, their exact roles are not fully understood. The physiological function of template activating factor (TAF)-I, one of the histone chaperones, also remains unclear; however, its biochemical properties have been well studied. By performing microarray analyses, we found that TAF-I stimulates the transcription of a sub-set of genes. The transcription of endogenous genes that was up-regulated by TAF-I was found to be additively stimulated by histone acetylation. On performing an experiment with a cell line containing a model gene integrated into the chromosome, TAF-I was found to stimulate the model gene transcription in a histone chaperone activity-dependent manner additively with histone acetylation. TAF-I bound to the core histones and remodeled the chromatin structure independent of the N-terminal histone tail and its acetylation level in vitro. These results suggest that TAF-I remodel the chromatin structure through its interaction with the core domain of the histones, including the histone fold, and this mechanism is independent of the histone acetylation status
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