62 research outputs found

    Aberrant \u3ci\u3eAZIN2\u3c/i\u3e and Polyamine Metabolism Precipitates Tau Neuropathology

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    Tauopathies display a spectrum of phenotypes from cognitive to affective behavioral impairments; however, mechanisms promoting tau pathology and how tau elicits behavioral impairment remain unclear. We report a unique interaction between polyamine metabolism, behavioral impairment, and tau fate. Polyamines are ubiquitous aliphatic molecules that support neuronal function, axonal integrity, and cognitive processing. Transient increases in polyamine metabolism hallmark the cell’s response to various insults, known as the polyamine stress response (PSR). Dysregulation of gene transcripts associated with polyamine metabolism in Alzheimer’s disease (AD) brains were observed, and we found that ornithine decarboxylase antizyme inhibitor 2 (AZIN2) increased to the greatest extent. We showed that sustained AZIN2 overexpression elicited a maladaptive PSR in mice with underlying tauopathy (MAPT P301S; PS19). AZIN2 also increased acetylpolyamines, augmented tau deposition, and promoted cognitive and affective behavioral impairments. Higher-order polyamines displaced microtubule-associated tau to facilitate polymerization but also decreased tau seeding and oligomerization. Conversely, acetylpolyamines promoted tau seeding and oligomers. These data suggest that tauopathies launch an altered enzymatic signature that endorses a feed-forward cycle of disease progression. Taken together, the tau-induced PSR affects behavior and disease continuance, but may also position the polyamine pathway as a potential entry point for plausible targets and treatments of tauopathy, including AD

    Life on the Ottoman Border: Essays in Honour of Nenad Moačanin

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    The articles written by friends, colleagues, former students, and one current doctoral student collected in this celebratory volume dedicated to the doyen of Ottoman studies in Croatia, Professor Nenad Moačanin, are divided into three main chapters entitled “Ottoman Bosnia, Turkish Croatia, and Turkey in Europe,” “Distant Borders and Regions,” and “Glimpses Beyond the Ottoman Border: Habsburg Croatia and the Republic of Dubrovnik.” The first section consists of the articles predominantly dedicated to the main fields of interests of Nenad Moačanin, namely social and economic history of the Ottoman Empire, with special focus on Ottoman Bosnia, the Balkans and Central Europe, as well as the Ottoman borderland in Croatia. The second section entitled “Distant Borders and Regions” brings three articles which are geographically remote from the Western Balkans and Central Europe, such as Crimea, Syria, and Palestine, but nevertheless fit well into the conception of the volume by offering a possibility for comparison of distant regions. The third section “Glimpses Beyond the Ottoman Border: Habsburg Croatia and the Republic of Dubrovnik” contains five articles which provide an important insight into the situation on “the other side.” The volume also includes a biographical overview of Professor Moačanin’s scientific and educational career at the beginning, and the bibliography at the end of the volume .The articles written by friends, colleagues, former students, and one current doctoral student collected in this celebratory volume dedicated to the doyen of Ottoman studies in Croatia, Professor Nenad Moačanin, are divided into three main chapters entitled “Ottoman Bosnia, Turkish Croatia, and Turkey in Europe,” “Distant Borders and Regions,” and “Glimpses Beyond the Ottoman Border: Habsburg Croatia and the Republic of Dubrovnik.” The first section consists of the articles predominantly dedicated to the main fields of interests of Nenad Moačanin, namely social and economic history of the Ottoman Empire, with special focus on Ottoman Bosnia, the Balkans and Central Europe, as well as the Ottoman borderland in Croatia. The second section entitled “Distant Borders and Regions” brings three articles which are geographically remote from the Western Balkans and Central Europe, such as Crimea, Syria, and Palestine, but nevertheless fit well into the conception of the volume by offering a possibility for comparison of distant regions. The third section “Glimpses Beyond the Ottoman Border: Habsburg Croatia and the Republic of Dubrovnik” contains five articles which provide an important insight into the situation on “the other side.” The volume also includes a biographical overview of Professor Moačanin’s scientific and educational career at the beginning, and the bibliography at the end of the volume

    Life on the Ottoman Border: Essays in Honour of Nenad Moačanin

    Get PDF
    The articles written by friends, colleagues, former students, and one current doctoral student collected in this celebratory volume dedicated to the doyen of Ottoman studies in Croatia, Professor Nenad Moačanin, are divided into three main chapters entitled “Ottoman Bosnia, Turkish Croatia, and Turkey in Europe,” “Distant Borders and Regions,” and “Glimpses Beyond the Ottoman Border: Habsburg Croatia and the Republic of Dubrovnik.” The first section consists of the articles predominantly dedicated to the main fields of interests of Nenad Moačanin, namely social and economic history of the Ottoman Empire, with special focus on Ottoman Bosnia, the Balkans and Central Europe, as well as the Ottoman borderland in Croatia. The second section entitled “Distant Borders and Regions” brings three articles which are geographically remote from the Western Balkans and Central Europe, such as Crimea, Syria, and Palestine, but nevertheless fit well into the conception of the volume by offering a possibility for comparison of distant regions. The third section “Glimpses Beyond the Ottoman Border: Habsburg Croatia and the Republic of Dubrovnik” contains five articles which provide an important insight into the situation on “the other side.” The volume also includes a biographical overview of Professor Moačanin’s scientific and educational career at the beginning, and the bibliography at the end of the volume .The articles written by friends, colleagues, former students, and one current doctoral student collected in this celebratory volume dedicated to the doyen of Ottoman studies in Croatia, Professor Nenad Moačanin, are divided into three main chapters entitled “Ottoman Bosnia, Turkish Croatia, and Turkey in Europe,” “Distant Borders and Regions,” and “Glimpses Beyond the Ottoman Border: Habsburg Croatia and the Republic of Dubrovnik.” The first section consists of the articles predominantly dedicated to the main fields of interests of Nenad Moačanin, namely social and economic history of the Ottoman Empire, with special focus on Ottoman Bosnia, the Balkans and Central Europe, as well as the Ottoman borderland in Croatia. The second section entitled “Distant Borders and Regions” brings three articles which are geographically remote from the Western Balkans and Central Europe, such as Crimea, Syria, and Palestine, but nevertheless fit well into the conception of the volume by offering a possibility for comparison of distant regions. The third section “Glimpses Beyond the Ottoman Border: Habsburg Croatia and the Republic of Dubrovnik” contains five articles which provide an important insight into the situation on “the other side.” The volume also includes a biographical overview of Professor Moačanin’s scientific and educational career at the beginning, and the bibliography at the end of the volume

    Tissue engineering of functional articular cartilage: the current status

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    Osteoarthritis is a degenerative joint disease characterized by pain and disability. It involves all ages and 70% of people aged >65 have some degree of osteoarthritis. Natural cartilage repair is limited because chondrocyte density and metabolism are low and cartilage has no blood supply. The results of joint-preserving treatment protocols such as debridement, mosaicplasty, perichondrium transplantation and autologous chondrocyte implantation vary largely and the average long-term result is unsatisfactory. One reason for limited clinical success is that most treatments require new cartilage to be formed at the site of a defect. However, the mechanical conditions at such sites are unfavorable for repair of the original damaged cartilage. Therefore, it is unlikely that healthy cartilage would form at these locations. The most promising method to circumvent this problem is to engineer mechanically stable cartilage ex vivo and to implant that into the damaged tissue area. This review outlines the issues related to the composition and functionality of tissue-engineered cartilage. In particular, the focus will be on the parameters cell source, signaling molecules, scaffolds and mechanical stimulation. In addition, the current status of tissue engineering of cartilage will be discussed, with the focus on extracellular matrix content, structure and its functionality

    Horizontal gene transfer in Histophilus somni and its role in the evolution of pathogenic strain 2336, as determined by comparative genomic analyses

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    <p>Abstract</p> <p>Background</p> <p>Pneumonia and myocarditis are the most commonly reported diseases due to <it>Histophilus somni</it>, an opportunistic pathogen of the reproductive and respiratory tracts of cattle. Thus far only a few genes involved in metabolic and virulence functions have been identified and characterized in <it>H. somni </it>using traditional methods. Analyses of the genome sequences of several <it>Pasteurellaceae </it>species have provided insights into their biology and evolution. In view of the economic and ecological importance of <it>H. somni</it>, the genome sequence of pneumonia strain 2336 has been determined and compared to that of commensal strain 129Pt and other members of the <it>Pasteurellaceae</it>.</p> <p>Results</p> <p>The chromosome of strain 2336 (2,263,857 bp) contained 1,980 protein coding genes, whereas the chromosome of strain 129Pt (2,007,700 bp) contained only 1,792 protein coding genes. Although the chromosomes of the two strains differ in size, their average GC content, gene density (total number of genes predicted on the chromosome), and percentage of sequence (number of genes) that encodes proteins were similar. The chromosomes of these strains also contained a number of discrete prophage regions and genomic islands. One of the genomic islands in strain 2336 contained genes putatively involved in copper, zinc, and tetracycline resistance. Using the genome sequence data and comparative analyses with other members of the <it>Pasteurellaceae</it>, several <it>H. somni </it>genes that may encode proteins involved in virulence (<it>e.g</it>., filamentous haemaggutinins, adhesins, and polysaccharide biosynthesis/modification enzymes) were identified. The two strains contained a total of 17 ORFs that encode putative glycosyltransferases and some of these ORFs had characteristic simple sequence repeats within them. Most of the genes/loci common to both the strains were located in different regions of the two chromosomes and occurred in opposite orientations, indicating genome rearrangement since their divergence from a common ancestor.</p> <p>Conclusions</p> <p>Since the genome of strain 129Pt was ~256,000 bp smaller than that of strain 2336, these genomes provide yet another paradigm for studying evolutionary gene loss and/or gain in regard to virulence repertoire and pathogenic ability. Analyses of the complete genome sequences revealed that bacteriophage- and transposon-mediated horizontal gene transfer had occurred at several loci in the chromosomes of strains 2336 and 129Pt. It appears that these mobile genetic elements have played a major role in creating genomic diversity and phenotypic variability among the two <it>H. somni </it>strains.</p

    Characteristics of Adults in the Hepatitis B Research Network in North America Reflect Their Country of Origin and Hepatitis B Virus Genotype

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    Chronic hepatitis B virus (HBV) infection is an important cause of cirrhosis and hepatocellular carcinoma worldwide; populations that migrate to the US and Canada might be disproportionately affected. The Hepatitis B Research Network (HBRN) is a cooperative network of investigators from the United States and Canada, created to facilitate clinical, therapeutic, and translational research in adults and children with hepatitis B. We describe the structure of the network and baseline characteristics of adults with hepatitis B enrolled in the network

    Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

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    Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

    Rıf'at 'Ali Abou-El-Haj, Formation of the Modern State: The Ottoman Empire Sixteenth to Eighteenth Centuries.

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    Donated by Klaus KreiserRıf'at 'Ali Abou-El-Haj, Formation of the Modern State: The Ottoman Empire Sixteenth to Eighteenth Centuries, SUNY Series in the Social and Economic History of the Middle East (Albany, N.Y.: SUNY Press, 1991). Pp. 172

    Historicizing the Ottoman Timar System: Identities of Timar-Holders, Fourteenth to Seventeenth Centuries

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    This article aims to develop a new narrative of changes in the Ottoman timar system independent of the complaints of decline brought by advice writers like Mustafa 'Ali. Based on the icmal defterleri, it examines the identities of timar-holders and their changes over time, a topic generally ignored in descriptions of the Ottoman military. Using data from earlier studies, it connects changes in timar-holding with changing conditions in the sultans' reigns. It then takes a longer-term look at these changes over the half-centuries and finds the well-known complaints in the nasihatnameler to be based on a very short-term view of the system.24 month embargo; published online: November 2017This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]
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