109 research outputs found

    Identification of Synaptic Targets of Drosophila Pumilio

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    Drosophila Pumilio (Pum) protein is a translational regulator involved in embryonic patterning and germline development. Recent findings demonstrate that Pum also plays an important role in the nervous system, both at the neuromuscular junction (NMJ) and in long-term memory formation. In neurons, Pum appears to play a role in homeostatic control of excitability via down regulation of para, a voltage gated sodium channel, and may more generally modulate local protein synthesis in neurons via translational repression of eIF-4E. Aside from these, the biologically relevant targets of Pum in the nervous system remain largely unknown. We hypothesized that Pum might play a role in regulating the local translation underlying synapse-specific modifications during memory formation. To identify relevant translational targets, we used an informatics approach to predict Pum targets among mRNAs whose products have synaptic localization. We then used both in vitro binding and two in vivo assays to functionally confirm the fidelity of this informatics screening method. We find that Pum strongly and specifically binds to RNA sequences in the 3′UTR of four of the predicted target genes, demonstrating the validity of our method. We then demonstrate that one of these predicted target sequences, in the 3′UTR of discs large (dlg1), the Drosophila PSD95 ortholog, can functionally substitute for a canonical NRE (Nanos response element) in vivo in a heterologous functional assay. Finally, we show that the endogenous dlg1 mRNA can be regulated by Pumilio in a neuronal context, the adult mushroom bodies (MB), which is an anatomical site of memory storage

    Identification of Synaptic Targets of Drosophila Pumilio

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    Drosophila Pumilio (Pum) protein is a translational regulator involved in embryonic patterning and germline development. Recent findings demonstrate that Pum also plays an important role in the nervous system, both at the neuromuscular junction (NMJ) and in long-term memory formation. In neurons, Pum appears to play a role in homeostatic control of excitability via down regulation of para, a voltage gated sodium channel, and may more generally modulate local protein synthesis in neurons via translational repression of eIF-4E. Aside from these, the biologically relevant targets of Pum in the nervous system remain largely unknown. We hypothesized that Pum might play a role in regulating the local translation underlying synapse-specific modifications during memory formation. To identify relevant translational targets, we used an informatics approach to predict Pum targets among mRNAs whose products have synaptic localization. We then used both in vitro binding and two in vivo assays to functionally confirm the fidelity of this informatics screening method. We find that Pum strongly and specifically binds to RNA sequences in the 3′UTR of four of the predicted target genes, demonstrating the validity of our method. We then demonstrate that one of these predicted target sequences, in the 3′UTR of discs large (dlg1), the Drosophila PSD95 ortholog, can functionally substitute for a canonical NRE (Nanos response element) in vivo in a heterologous functional assay. Finally, we show that the endogenous dlg1 mRNA can be regulated by Pumilio in a neuronal context, the adult mushroom bodies (MB), which is an anatomical site of memory storage

    Noncutaneous malignant melanoma: a prognostic model from a retrospective multicenter study

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    Abstract Background We performed multicenter study to define clinical characteristics of noncutaneous melanomas and to establish prognostic factors patients who received curative resection. Methods Of the 141 patients who were diagnosed of non-cutaneous melanoma at 4 institutions in Korea between June 1992 and May 2005, 129 (91.5%) satisfied the selection criteria. Results Of the 129 noncutaneous melanoma patients, 14 patients had ocular melanoma and 115 patients had mucosal melanoma. For mucosal melanoma, anorectum was the most common anatomic site (n = 39, 30.2%) which was followed by nasal cavity (n = 30, 23.3%), genitourinary (n = 21, 16.3%), oral cavity (n = 14, 10.9%), upper gastrointestinal tract (n = 6, 4.7%) and maxillary sinus (n = 5, 3.9%) in the order of frequency. With the median 64.5 (range 4.3-213.0) months follow-up, the median overall survival were 24.4 months (95% CI 13.2-35.5) for all patients, and 34.6 (95% CI 24.5-44.7) months for curatively resected mucosal melanoma patients. Adverse prognostic factors of survival for 87 curatively resected mucosal melanoma patients were complete resection (R1 resection margin), and age > 50 years. For 14 ocular melanoma, Survival outcome was much better than mucosal melanoma with 73.3% of 2 year OS and 51.2 months of median OS (P = .04). Conclusion Prognosis differed according to primary sites of noncutaneous melanoma. Based on our study, noncutaneous melanoma patients should be treated differently to improve survival outcome.Peer Reviewe

    Parental Height Differences Predict the Need for an Emergency Caesarean Section

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    More than 30% of all pregnancies in the UK require some form of assistance at delivery, with one of the more severe forms of assistance being an emergency Caesarean section (ECS). Previously it has been shown that the likelihood of a delivery via ECS is positively associated with the birth weight and size of the newborn and negatively with maternal height. Paternal height affects skeletal growth and mass of the fetus, and thus might also affect pregnancy outcomes. We hypothesized that the effect of newborn birth weight on the risk of ECS would decrease with increasing maternal height. Similarly, we predicted that there would be an increase in ECS risk as a function of paternal height, but that this effect would be relative to maternal height (i.e., parental height differences). We used data from the Millennium Cohort Study: a large-scale survey (N = 18,819 births) with data on babies born and their parents from the United Kingdom surveyed 9 to 12-months after birth. We found that in primiparous women, both maternal height and parental height differences interacted with birth weight and predicted the likelihood of an ECS. When carrying a heavy newborn, the risk of ECS was more than doubled for short women (46.3%) compared to tall women (21.7%), in agreement with earlier findings. For women of average height carrying a heavy newborn while having a relatively short compared to tall partner reduced the risk by 6.7%. In conclusion, the size of the baby, the height of the mother and parental height differences affect the likelihood of an ECS in primiparous women

    Trace Elements and Carbon and Nitrogen Stable Isotopes in Organisms from a Tropical Coastal Lagoon

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    Trace elements (Fe, Mn, Al, Zn, Cr, Cu, Ni, Pb, Cd, Hg, and As) and stable isotope ratios (δ13C and δ15N) were analyzed in sediments, invertebrates, and fishes from a tropical coastal lagoon influenced by iron ore mining and processing activities to assess the differences in trace element accumulation patterns among species and to investigate relations with trophic levels of the organisms involved. Overall significant negative relations between trophic level (given by 15N) and trace element concentrations in gastropods and crustaceans showed differences in internal controls of trace element accumulation among the species of different trophic positions, leading to trace element dilution. Generally, no significant relation between δ15N and trace element concentrations was observed among fish species, probably due to omnivory in a number of species as well as fast growth. Trace element accumulation was observed in the fish tissues, with higher levels of most trace elements found in liver compared with muscle and gill. Levels of Fe, Mn, Al, and Hg in invertebrates, and Fe and Cu in fish livers, were comparable with levels in organisms and tissues from other contaminated areas. Trace element levels in fish muscle were below the international safety baseline standards for human consumption

    From DPSIR the DAPSI(W)R(M) Emerges… a Butterfly – ‘protecting the natural stuff and delivering the human stuff’

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    The complexity of interactions and feedbacks between human activities and ecosystems can make the analysis of such social-ecological systems intractable. In order to provide a common means to understand and analyse the links between social and ecological process within these systems, a range of analytical frameworks have been developed and adopted. Following decades of practical experience in implementation, the Driver Pressure State Impact Response (DPSIR) conceptual framework has been adapted and re-developed to become the D(A)PSI(W)R(M). This paper describes in detail the D(A)PSI(W)R(M) and its development from the original DPSIR conceptual frame. Despite its diverse application and demonstrated utility, a number of inherent shortcomings are identified. In particular the DPSIR model family tend to be best suited to individual environmental pressures and human activities and their resulting environmental problems, having a limited focus on the supply and demand of benefits from nature. We present a derived framework, the “Butterfly”, a more holistic approach designed to expand the concept. The “Butterfly” model, moves away from the centralised accounting framework approach while more-fully incorporating the complexity of social and ecological systems, and the supply and demand of ecosystem services, which are central to human-environment interactions

    Beyond the university : higher education institutions across time and space

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    This chapter makes the case for a history of higher education institutions which looks beyond the university. Building on recent historiographical developments, it argues that the history of higher education must not be limited to the history of the university, an institution fixed in space and time, but must rather adopt a transnational and transhistorical approach. It also argues for a broader definition of “institution” which includes concepts, ideas, and practices which have become “institutionalized” alongside traditional understandings of institutions as sites with fixed locations and physical forms. Beginning with an exploration of higher education and learning across the globe in the ancient world, it goes on to study significant developments in higher education during the medieval, Renaissance, Enlightenment, and modern periods. While considerable attention is paid to the development of the university in Europe and around the world, the role and significance of other higher education institutions are stressed throughout. Particular weight is placed on the importance of learned societies and academies as sites of research development and training in the late eighteenth and nineteenth centuries. The chapter concludes with reflections on the ways in which the prominence of the research university since the Second World War has shaped the writing of the history of higher education in recent years, most notably, the dominant position given to the university as institution. Potentially fruitful directions for future research are also discussed, in particular, the need to focus on alternative higher education institutions
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