309 resultados para post-translational modifications


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In April 2014, the World Health Organization announced the beginning of a post-antibiotic era and declared antimicrobial resistance (AMR) a public health priority demanding global action. If no action is taken, by 2050 AMR will kill more people each year than cancer, with 10 million estimated annual deaths at a cost of $100 trillion to the global economy. New therapies to tackle multidrug resistant bacterial pathogens are urgently needed. Unlike traditional antibiotics, antivirulence drugs inhibit bacterial virulence instead of growth promising to offer a new class of superior therapeutics that will be ‘evolution-proof’ and ‘tailored-spectrum’. This mini-review discusses the latest emerging evidence on the promised benefits of antivirulence drugs over conventional antibiotics, also highlighting the challenges in evaluating these properties for each of the diverse virulence targets that are currently under investigation. The author argues that overcoming such challenges early in the development process constitutes an important step towards successfully progressing each of the expanding number of antivirulence strategies into next-generation therapies for common human and animal infections that are becoming increasingly refractory to all available antibiotics.

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This paper by Carl Grodach demonstrates the careful unravelling of complexity, diversity, contestation and contradictions involved in the reconstruction of symbolic urban spaces after violent conflict, and the allied processes of cultural reinterpretation, political reconfiguration and material revaluation which accompany it. The paper analyses the reconstruction and redevelopment of the 16th-century historic centre of Mostar, Bosnia-Herzegovina, following the Bosnian Wars of 1992–1995. Reconstruction efforts centre around Stari Most, the 16th-century Ottoman bridge destroyed by Bosnian Croat military in 1993. In Mostar, both international and local organizations are in the process of reinterpreting Bosnia’s legacy of Ottoman city spaces. This research and analysis illuminates how such spaces can be central to contemporary projects to redefine group identities and conceptions of place. It provides insight into the ways various groups are attempting to reshape outside perceptions of the city—and Bosnia’s ethnic conflict—to articulate a new definition of local identity and ethnic relations and to remake a stable tourist economy through Mostar’s urban spaces.

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This chapter examines the burgeoning field of dramaturgy in Australian performance and suggests that the growth of the both the profession and the practices of dramaturgy were a result of structural changes arising from the policies of the Howard Government, globalism and economic rationalism, as well as the demographic pressures of generational reform.

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Purpose: We investigated if oral ingestion of ibuprofen influenced leucocyte recruitment and infiltration following an acute bout of traditional resistance exercise Methods: Sixteen male subjects were divided into two groups that received the maximum over-the-counter dose of ibuprofen (1200mg d−1) or a similarly administered placebo following lower body resistance exercise. Muscle biopsies were taken from m.vastus lateralis and blood serum samples were obtained before and immediately after exercise, and at 3 and 24 h after exercise. Muscle cross-sections were stained with antibodies against neutrophils (CD66b and MPO) and macrophages (CD68). Muscle damage was assessed via creatine kinase and myoglobin in blood serum samples, and muscle soreness was rated on a ten-point pain scale. Results: The resistance exercise protocol stimulated a significant increase in the number of CD66b+ and MPO+ cells when measured 3 h post exercise. Serum creatine kinase, myoglobin and subjective muscle soreness all increased post-exercise. Muscle leucocyte infiltration, creatine kinase, myoglobin and subjective muscle soreness were unaffected by ibuprofen treatment when compared to placebo. There was also no association between increases in inflammatory leucocytes and any other marker of cellular muscle damage. Conclusion: Ibuprofen administration had no effect on the accumulation of neutrophils, markers of muscle damage or muscle soreness during the first 24 h of post-exercise muscle recovery.

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‘Soft power’ has been a concept that has generated great political and scholarly interest in China, as it raises the question of how to achieve cultural standing commensurate with the nation’s growing economic significance. But from the perspectives of communication and cultural studies, we can identify limits with both ‘soft power’ as a concept and how it understands culture and communication, and the assumptions made about the capacities of state cultural promotion through media to appeal to global audiences. Drawing upon case studies of the United States, the United Kingdom, Russia, India, Japan and South Korea, this article identified challenges and opportunities for China in growing its international cultural soft power in a ‘post-globalisation’ era.

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The existing clinical biomarkers for prostate cancer (PCa) are not ideal, since they cannot specifically differentiate between those patients who should be treated immediately and those who should avoid overtreatment. Current screening techniques lack specificity, and a decisive diagnosis of PCa is based on prostate biopsy. Although PCa screening is widely utilized nowadays, two-thirds of the biopsies performed are still unnecessary. Thus, the discovery of noninvasive PCa biomarkers remains an urgent unmet medical need. Once metastasized, there is still no curative therapy. A better understanding of sustained androgen receptor signalling in castration resistant prostate cancer (CRPC) has now led to the development of more effective therapies. We need a better understanding of the molecular and cellular aspects of prostate carcinogenesis and progression. Identification of cancer initiating cells and therapies against these populations is a promising way forward to fight this disease.

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Richard Lewontin proposed that the ability of a scientific field to create a narrative for public understanding garners it social relevance. This article applies Lewontin's conceptual framework of the functions of science (manipulatory and explanatory) to compare and explain the current differences in perceived societal relevance of genetics/genomics and proteomics. We provide three examples to illustrate the social relevance and strong cultural narrative of genetics/genomics for which no counterpart exists for proteomics. We argue that the major difference between genetics/genomics and proteomics is that genomics has a strong explanatory function, due to the strong cultural narrative of heredity. Based on qualitative interviews and observations of proteomics conferences, we suggest that the nature of proteins, lack of public understanding, and theoretical complexity exacerbates this difference for proteomics. Lewontin's framework suggests that social scientists may find that omics sciences affect social relations in different ways than past analyses of genetics.

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This article examines the merger between AOL and the Huffington Post. The broader issues around the merger will be investigated, especially the implication for rights, in particular free expression, and their conditions for exercise and actual exercise online. One major issue is that of the status of user-generated content and how the existing legal regime reflects the ethical concerns of users over how their content, data and information is used and commodified by the for-profit Internet intermediaries and platforms, especially when they start to merge and form concentrations. The extent to which the current legal regimes, especially human rights, deal with these problems in an adequate fashion will be assessed, along with the presentation of some suggestions of alternative approaches which may be more effective in practice.

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The business value of information technology (IT) is realized through the continuous use of IT subsequent to users’ adoption. Understanding post-adoptive IT usage is useful in realizing potential IT business value. Most previous research on post-adoptive IT usage, however, dismisses the unintentional and unconscious aspects of usage behavior. This paper advances understanding of the unintentional, unconscious, and thereby automatic usage of IT features during the post-adoptive stage. Drawing from Social Psychology literature, we argue human behaviors can be triggered by environmental cues and directed by the person’s mental goals, thereby operating without a person’s consciousness and intentional will. On this basis, we theorize the role of a user’s innovativeness goal, as the desired state of an act to innovate, in directing the user’s unintentional, unconscious, and automatic post-adoptive IT feature usage behavior. To test the hypothesized mechanisms, a human experiment employing a priming technique, is described.