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Biophysical Characterization of Alpha-Synuclein Membrane Binding Modes Determined by Membrane Properties
No full textAlpha-Synuclein (aSyn) is an intrinsically disordered neuronal protein that forms an amphipathic helix when it peripherally binds to lipid membranes. This protein is associated with Parkinson’s Disease (PD) and despite decades of research, the physiological function of aSyn is still not entirely understood. The evidence strongly supports the interaction of aSyn with neuronal membranes to be integral to its function, motivating the careful study of its membrane-binding behavior. Thus, this thesis aims to understand this interaction in greater detail through understanding how the binding modes of the protein change with lipid composition and PD-associated mutants, and how other physiologically relevant properties such as protein concentration, osmotic stress, and calcium ions affect the membrane binding behavior. Overall, we demonstrate that even small changes in membrane properties can have downstream effects that could be physiologically relevant
Amédée Jaubert’s Elements de la Grammaire Turke
No full text17. yüzyılda Jaubert tarafından hazırlanmış olan gramer kitabı Elements de la Grammaire Turke Avrupa dillerinin Türkçeyle olan münasebetine ışık tutan eserlerden biridir. Latin harfleriyle yazılan bu eserdeki çalışmada ilk olarak müellif, içerik ve üslup hakkında bilgi verilmiştir. Daha sonra ise eser ayrıntılı bir şekilde çözümlenmiştir. Müellif esere Uyarı (5.-9. s.) ve Giriş (11.-15. s.) ile başlayarak eseri üç bölümde nihayete erdirmiştir. Eserin 1. bölümünde (17. s.) alfabe, isimler, sayılar ve zamirler; 2. bölümünde (87. s.) fiiller, edatlar, zarflar, bağlaçlar ve ünlemler; 3. bölümünde (211. s.) sentaks, kelimelerin ilişkilerine uyacak şekilde seçilen isimlerin ve işaretlerin düzeni ve fiiller üzerine genel örnekler kaleme alınmıştır. Eserde bu bölümler dışında ek (223. s.), diyaloglar (229. s.), kelimeler (269. s.) ve atasözleri (335. s.) metni kaleme alınmıştır. Hazırlanan bu çalışma ile 17. yüzyılın Türkiye Türkçesinin söz varlığı, ses, biçim, cümle yapısı ve müellifin kimliği gün yüzüne çıkarılmaya çalışılmıştır.Elements de la Grammaire Turke is one of the works which shed light on the relation of European langues with Turkish. In this work written in Latin letters, information was given about the author, content and wording. Then the work was solved in detail. The author completes his work in three chapters, beginning with the Warning (5.-9. p.) and Introduction (11.-15. p.). Alphabet, nouns, numbers and pronouns in chapter first of the work (17. p.); verbs, prepositions, adverbs, conjuctions and interjection in chapter second (87. p.); syntax, the order of names and signs to match the relations of word and general examples on verbs in chapter third (211. p.) has been received. In addition to these chapters, The Additions (223. p.), The Dialogues (229. p.), The Words (269. p.) and The Proverbs (335. p.) were written in the work. This study was prepared 17th century of Turkey Turkish with phonetics, morphology, syntax and personality of the author have been tried to evaluate
Adrenergic Agonists Bind to Adrenergic-Receptor-Like Regions of the Mu Opioid Receptor, Enhancing Morphine and Methionine-Enkephalin Binding: A New Approach to “Biased Opioids”?
No full textfirst_pageDownload PDFsettingsOrder Article ReprintsOpen AccessArticleAdrenergic Agonists Bind to Adrenergic-Receptor-Like Regions of the Mu Opioid Receptor, Enhancing Morphine and Methionine-Enkephalin Binding: A New Approach to “Biased Opioids”?by Robert Root-Bernstein1,* [ORCID] , Miah Turke1, Udaya K. Tiruttani Subhramanyam2,3, Beth Churchill1 and Joerg Labahn2,31Department of Physiology, Michigan State University, 567 Wilson Road, Room 2201 Biomedical and Physical Sciences Building, East Lansing, MI 48824, USA2Centre for Structural Systems Biology (CSSB), Notkestraße 85, 22607 Hamburg, Germany3Forschungszentrum Juelich GmbH, ICS-6, 52425 Juelich, Germany*Author to whom correspondence should be addressed.Int. J. Mol. Sci. 2018, 19(1), 272; https://doi.org/10.3390/ijms19010272Submission received: 8 December 2017 / Revised: 10 January 2018 / Accepted: 13 January 2018 / Published: 17 January 2018(This article belongs to the Section Bioactives and Nutraceuticals)Downloadkeyboard_arrow_downBrowse FiguresVersions NotesAbstractExtensive evidence demonstrates functional interactions between the adrenergic and opioid systems in a diversity of tissues and organs. While some effects are due to receptor and second messenger cross-talk, recent research has revealed an extracellular, allosteric opioid binding site on adrenergic receptors that enhances adrenergic activity and its duration. The present research addresses whether opioid receptors may have an equivalent extracellular, allosteric adrenergic binding site that has similar enhancing effects on opioid binding. Comparison of adrenergic and opioid receptor sequences revealed that these receptors share very significant regions of similarity, particularly in some of the extracellular and transmembrane regions associated with adrenergic binding in the adrenergic receptors. Five of these shared regions from the mu opioid receptor (muOPR) were synthesized as peptides and tested for binding to adrenergic, opioid and control compounds using ultraviolet spectroscopy. Adrenergic compounds bound to several of these muOPR peptides with low micromolar affinity while acetylcholine, histamine and various adrenergic antagonists did not. Similar studies were then conducted with purified, intact muOPR with similar results. Combinations of epinephrine with methionine enkephalin or morphine increased the binding of both by about half a log unit. These results suggest that muOPR may be allosterically enhanced by adrenergic agonists
Glutathione and Glutathione-Like Sequences of Opioid and Aminergic Receptors Bind Ascorbic Acid, Adrenergic and Opioid Drugs Mediating Antioxidant Function: Relevance for Anesthesia and Abuse
No full textOpioids and their antagonists alter vitamin C metabolism. Morphine binds to glutathione (l-γ-glutamyl-l-cysteinyl-glycine), an intracellular ascorbic acid recycling molecule with a wide range of additional activities. The morphine metabolite morphinone reacts with glutathione to form a covalent adduct that is then excreted in urine. Morphine also binds to adrenergic and histaminergic receptors in their extracellular loop regions, enhancing aminergic agonist activity. The first and second extracellular loops of adrenergic and histaminergic receptors are, like glutathione, characterized by the presence of cysteines and/or methionines, and recycle ascorbic acid with similar efficiency. Conversely, adrenergic drugs bind to extracellular loops of opioid receptors, enhancing their activity. These observations suggest functional interactions among opioids and amines, their receptors, and glutathione. We therefore explored the relative binding affinities of ascorbic acid, dehydroascorbic acid, opioid and adrenergic compounds, as well as various control compounds, to glutathione and glutathione-like peptides derived from the extracellular loop regions of the human beta 2-adrenergic, dopamine D1, histamine H1, and mu opioid receptors, as well as controls. Some cysteine-containing peptides derived from these receptors do bind ascorbic acid and/or dehydroascorbic acid and the same peptides generally bind opioid compounds. Glutathione binds not only morphine but also naloxone, methadone, and methionine enkephalin. Some adrenergic drugs also bind to glutathione and glutathione-like receptor regions. These sets of interactions provide a novel basis for understanding some ways that adrenergic, opioid and antioxidant systems interact during anesthesia and drug abuse and may have utility for understanding drug interactions
Investigating the effects of recency and size of training text on author recognition problem
No full text19th International Symposium on Computer and Information Sciences (ISCIS 2004) -- OCT 27-29, 2004 -- Kemer Antalya, TURKEYPrediction by partial match (PPM) is an effective tool to address the author recognition problem. In this study, we have successfully applied the trained PPM technique for author recognition on Turkish texts. Furthermore, we have investigated the effects of recency, as well as size of the training text on the performance of the PPM approach. Results show that, more recent and larger training texts help decrease the compression rate, which, in turn, leads to increased success in author recognition. Comparing the effects of the recency and the size of the training text, we see that the size factor plays a more dominant role on the performance.Bilkent Univ, Dept Comp Engn, Inst Elect & Elect Engineers Turkey Sect, Working Grp, Int Federat Informat Proc, Sci & Tech Res Council Turke
Navoi and Turkish Criticism
No full textIn the article, the author provides information about Navoi's work, in particular, works of this genre created in Turkey under the influence of his tazkira. He tries to scientifically substantiate their significance by analyzing the tazkirs created in Turke
Adrenergic Agonists Bind to Adrenergic-Receptor-Like Regions of the Mu Opioid Receptor, Enhancing Morphine and Methionine-Enkephalin Binding: A New Approach to "Biased Opioids"?
No full textExtensive evidence demonstrates functional interactions between the adrenergic and opioid systems in a diversity of tissues and organs. While some effects are due to receptor and second messenger cross-talk, recent research has revealed an extracellular, allosteric opioid binding site on adrenergic receptors that enhances adrenergic activity and its duration. The present research addresses whether opioid receptors may have an equivalent extracellular, allosteric adrenergic binding site that has similar enhancing effects on opioid binding. Comparison of adrenergic and opioid receptor sequences revealed that these receptors share very significant regions of similarity, particularly in some of the extracellular and transmembrane regions associated with adrenergic binding in the adrenergic receptors. Five of these shared regions from the mu opioid receptor (muOPR) were synthesized as peptides and tested for binding to adrenergic, opioid and control compounds using ultraviolet spectroscopy. Adrenergic compounds bound to several of these muOPR peptides with low micromolar affinity while acetylcholine, histamine and various adrenergic antagonists did not. Similar studies were then conducted with purified, intact muOPR with similar results. Combinations of epinephrine with methionine enkephalin or morphine increased the binding of both by about half a log unit. These results suggest that muOPR may be allosterically enhanced by adrenergic agonists. View Full-Text Keywords: biased opioids; morphine; methionine-enkephalin; epinephrine; norepinephrine; enhancement; synergy; allosteric; mu opioid receptor; receptor dimers; dimerizatio
<i>Clostridia</i> and Enteroviruses as Synergistic Triggers of Type 1 Diabetes Mellitus
No full textWhat triggers type 1 diabetes mellitus (T1DM)? One common assumption is that triggers are individual microbes that mimic autoantibody targets such as insulin (INS). However, most microbes highly associated with T1DM pathogenesis, such as coxsackieviruses (COX), lack INS mimicry and have failed to induce T1DM in animal models. Using proteomic similarity search techniques, we found that COX actually mimicked the INS receptor (INSR). Clostridia were the best mimics of INS. Clostridia antibodies cross-reacted with INS in ELISA experiments, confirming mimicry. COX antibodies cross-reacted with INSR. Clostridia antibodies further bound to COX antibodies as idiotype–anti-idiotype pairs conserving INS–INSR complementarity. Ultraviolet spectrometry studies demonstrated that INS-like Clostridia peptides bound to INSR-like COX peptides. These complementary peptides were also recognized as antigens by T cell receptor sequences derived from T1DM patients. Finally, most sera from T1DM patients bound strongly to inactivated Clostridium sporogenes, while most sera from healthy individuals did not; T1DM sera also exhibited evidence of anti-idiotype antibodies against idiotypic INS, glutamic acid decarboxylase, and protein tyrosine phosphatase non-receptor (islet antigen-2) antibodies. These results suggest that T1DM is triggered by combined enterovirus-Clostridium (and possibly combined Epstein–Barr-virus-Streptococcal) infections, and the probable rate of such co-infections approximates the rate of new T1DM diagnoses
Some properties of the weak subdifferential
No full textSome properties of the weak subdifferential is considered in this paper. By using definitioan and properties of the weak subdifferential which described in the papers [1, 2, 3], the author prove some theorem connectiong weak subdifferential in nonsmooth aYasar University, Turke
Challenges in analyzing unstructured learner generated qualitative big data
No full textAs the amount of educational data grows, a necessity is occurring to define characteristics of Unstructured Learner Generated Qualitative Big Data (ULGQBD), and develop a conceptual framework to analyze these data sets. According to the author there are tFaculty of Communication, Yasar University, Izmir, Turke
