49 research outputs found

    An S-Palmitoyltransferase Modulates P2X7 Function

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    The P2X7 receptor is an ATP gated ion channel that plays significant roles in the immune response and neurodegeneration. In a heterologous system, P2X7 channels open only when triggered by a high concentration of ATP (EC50 [ALMOST EQUAL TO] 100 to 1000 [MICRO SIGN]M), suggesting that P2X7 receptors may function under pathological conditions. However, it remains unclear whether P2X7 functions under physiological conditions, in which extracellular concentrations of ATP are generally much lower. Here, I show that interaction with DHHC11, a palmitoyltransferase, modifies P2X7 gating in a manner independent from its palmitoyltransferase activity. This interaction sensitizes the P2X7 receptor to lower concentrations of ATP and slows its activation and deactivation, but does not affect the so-called "dilated state" where the P2X7 channel becomes permeable to large cations. Modified P2X7 currents were still seen with deletion of the P2X7 N- and C- termini, as well as with the deletions of the DHHC11 termini. I developed a computational Markov state model and successfully replicated the observed modifications of the P2X7 receptor by DHHC11. This represents a potential interaction between P2X7 and DHHC11, which implies yet undiscovered roles of P2X7 receptor under physiological conditions

    Effects of a Government-Academic Partnership: Has the NSF-Census Bureau Research Network Helped Improve the U.S. Statistical System?

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    The National Science Foundation-Census Bureau Research Network (NCRN) was established in 2011 to create interdisciplinary research nodes on methodological questions of interest and significance to the broader research community and to the Federal Statistical System (FSS), particularly to the Census Bureau. The activities to date have covered both fundamental and applied statistical research and have focused at least in part on the training of current and future generations of researchers in skills of relevance to surveys and alternative measurement of economic units, households, and persons. This article focuses on some of the key research findings of the eight nodes, organized into six topics: (1) improving census and survey data-quality and data collection methods; (2) using alternative sources of data; (3) protecting privacy and confidentiality by improving disclosure avoidance; (4) using spatial and spatio-temporal statistical modeling to improve estimates; (5) assessing data cost and data-quality tradeoffs; and (6) combining information from multiple sources. The article concludes with an evaluation of the ability of the FSS to apply the NCRN’s research outcomes, suggests some next steps, and discusses the implications of this research-network model for future federal government research initiatives

    On the role of theory and modeling in neuroscience

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    In recent years, the field of neuroscience has gone through rapid experimental advances and extensive use of quantitative and computational methods. This accelerating growth has created a need for methodological analysis of the role of theory and the modeling approaches currently used in this field. Toward that end, we start from the general view that the primary role of science is to solve empirical problems, and that it does so by developing theories that can account for phenomena within their domain of application. We propose a commonly-used set of terms - descriptive, mechanistic, and normative - as methodological designations that refer to the kind of problem a theory is intended to solve. Further, we find that models of each kind play distinct roles in defining and bridging the multiple levels of abstraction necessary to account for any neuroscientific phenomenon. We then discuss how models play an important role to connect theory and experiment, and note the importance of well-defined translation functions between them. Furthermore, we describe how models themselves can be used as a form of experiment to test and develop theories. This report is the summary of a discussion initiated at the conference Present and Future Theoretical Frameworks in Neuroscience, which we hope will contribute to a much-needed discussion in the neuroscientific community

    Neuroendocrine–immune disequilibrium and endometriosis: an interdisciplinary approach

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    Endometriosis, a chronic disease characterized by endometrial tissue located outside the uterine cavity, affects one fourth of young women and is associated with chronic pelvic pain and infertility. However, an in-depth understanding of the pathophysiology and effective treatment strategies of endometriosis is still largely elusive. Inadequate immune and neuroendocrine responses are significantly involved in the pathophysiology of endometriosis, and key findings are summarized in the present review. We discuss here the role of different immune mechanisms particularly adhesion molecules, protein–glycan interactions, and pro-angiogenic mediators in the development and progression of the disease. Finally, we introduce the concept of endometrial dissemination as result of a neuroendocrine-immune disequilibrium in response to high levels of perceived stress caused by cardinal clinical symptoms of endometriosis

    26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

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    This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)

    A História da Alimentação: balizas historiogråficas

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    Os M. pretenderam traçar um quadro da HistĂłria da Alimentação, nĂŁo como um novo ramo epistemolĂłgico da disciplina, mas como um campo em desenvolvimento de prĂĄticas e atividades especializadas, incluindo pesquisa, formação, publicaçÔes, associaçÔes, encontros acadĂȘmicos, etc. Um breve relato das condiçÔes em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biolĂłgica, a econĂŽmica, a social, a cultural e a filosĂłfica!, assim como da identificação das contribuiçÔes mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histĂłrica, foi ela organizada segundo critĂ©rios morfolĂłgicos. A seguir, alguns tĂłpicos importantes mereceram tratamento Ă  parte: a fome, o alimento e o domĂ­nio religioso, as descobertas europĂ©ias e a difusĂŁo mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rĂĄpido balanço crĂ­tico da historiografia brasileira sobre o tema

    Effects of a Government-Academic Partnership: Has the NSF-Census Bureau Research Network Helped Improve the U.S. Statistical System?

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    The National Science Foundation-Census Bureau Research Network (NCRN) was established in 2011 to create interdisciplinary research nodes on methodological questions of interest and significance to the broader research community and to the Federal Statistical System (FSS), particularly to the Census Bureau. The activities to date have covered both fundamental and applied statistical research and have focused at least in part on the training of current and future generations of researchers in skills of relevance to surveys and alternative measurement of economic units, households, and persons. This article focuses on some of the key research findings of the eight nodes, organized into six topics: (1) improving census and survey data-quality and data collection methods; (2) using alternative sources of data; (3) protecting privacy and confidentiality by improving disclosure avoidance; (4) using spatial and spatio-temporal statistical modeling to improve estimates; (5) assessing data cost and data-quality tradeoffs; and (6) combining information from multiple sources. The article concludes with an evaluation of the ability of the FSS to apply the NCRN’s research outcomes, suggests some next steps, and discusses the implications of this research-network model for future federal government research initiatives

    Effects of a Government-Academic Partnership: Has the NSF-Census Bureau Research Network Helped Improve the U.S. Statistical System?

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    This paper began as a May 8, 2015 presentation to the National Academies of Science’s Committee on National Statistics by two of the principal investigators of the National Science Foundation-Census Bureau Research Network (NCRN) – John Abowd and the late Steve Fienberg (Carnegie Mellon University). The authors acknowledge the contributions of the other principal investigators of the NCRN who are not co-authors of the paper (William Block, William Eddy, Alan Karr, Charles Manski, Nicholas Nagle, and Rebecca Nugent), the co- principal investigators, and the comments of Patrick Cantwell, Constance Citro, Adam Eck, Brian Harris-Kojetin, and Eloise Parker. We note with sorrow the deaths of Stephen Fienberg and Allan McCutcheon, two of the original NCRN principal investigators. The principal investigators also wish to acknowledge Cheryl Eavey’s sterling grant administration on behalf of the NSF. The conclusions reached in this paper are not the responsibility of the National Science Foundation (NSF), the Census Bureau, or any of the institutions to which the authors belongThe National Science Foundation-Census Bureau Research Network (NCRN) was established in 2011 to create interdisciplinary research nodes on methodological questions of interest and significance to the broader research community and to the Federal Statistical System (FSS), particularly the Census Bureau. The activities to date have covered both fundamental and applied statistical research and have focused at least in part on the training of current and future generations of researchers in skills of relevance to surveys and alternative measurement of economic units, households, and persons. This paper discusses some of the key research findings of the eight nodes, organized into six topics: (1) Improving census and survey data collection methods; (2) Using alternative sources of data; (3) Protecting privacy and confidentiality by improving disclosure avoidance; (4) Using spatial and spatio-temporal statistical modeling to improve estimates; (5) Assessing data cost and quality tradeoffs; and (6) Combining information from multiple sources. It also reports on collaborations across nodes and with federal agencies, new software developed, and educational activities and outcomes. The paper concludes with an evaluation of the ability of the FSS to apply the NCRN’s research outcomes and suggests some next steps, as well as the implications of this research-network model for future federal government renewal initiatives.NSF-1129475 to Northwestern University; NSF-1130706 to Carnegie Mellon University; NSF-1131500 to University of Michigan-Ann Arbor; NSF-1131848 to Cornell University; NSF-1131897 to Duke University and National Institute of Statistical Sciences (NISS); NSF-1132008 to University of Colorado-Boulder; NSF-1132015 to University of Nebraska-Lincoln; NSF-1132031 to University of Missouri; and NSF-1507241 for the Coordinating Office (Cornell, Duke, and NISS).https://dx.doi.org/10.1093/jssam/smy02

    Millimeter-scale ridges increase the duration of larval settling windows.

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    (a) Visualization of the relative fluid speed over flat (left) and ridged (right) substrates during peak (top) and turning point (bottom) flow. The fluid velocity (U) is normalized by the average larval swimming velocity (uℓ). Dotted black boxes represent regions ≀1.5 mm above the substrate surface that were used to calculate duration of settlement windows. Black arrows near the bottoms of the ridges indicate regions where the velocity remains low even at the turning points. (b) The average relative flow speed within the dotted black regions plotted over an average period for flat (top) and ridged (bottom) substrates. The yellow regions highlight the settling windows during which the local flow speed drops below uℓ (black line) plus one standard deviation (grey band).</p
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