An S-Palmitoyltransferase Modulates P2X7 Function

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?

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

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

Temperature and spatial connectivity drive patterns in freshwater macroinvertebrate diversity across the Arctic

Warming in the Arctic is predicted to change freshwater biodiversity through loss of unique taxa and northward range expansion of lower latitude taxa. Detecting such changes requires establishing circumpolar baselines for diversity, and understanding the primary drivers of diversity. We examined benthic macroinvertebrate diversity using a circumpolar dataset of &gt;1,500 Arctic lake and river sites. Rarefied α diversity within catchments was assessed along latitude and temperature gradients. Community composition was assessed through region-scale analysis of β diversity and its components (nestedness and turnover), and analysis of biotic–abiotic relationships. Rarefied α diversity of lakes and rivers declined with increasing latitude, although more strongly across mainland regions than islands. Diversity was strongly related to air temperature, with the lowest diversity in the coldest catchments. Regional dissimilarity was highest when mainland regions were compared with islands, suggesting that connectivity limitations led to the strongest dissimilarity. High contributions of nestedness indicated that island regions contained a subset of the taxa found in mainland regions. High Arctic rivers and lakes were predominately occupied by Chironomidae and Oligochaeta, whereas Ephemeroptera, Plecoptera, and Trichoptera taxa were more abundant at lower latitudes. Community composition was strongly associated with temperature, although geology and precipitation were also important correlates. The strong association with temperature supports the prediction that warming will increase Arctic macroinvertebrate diversity, although low diversity on islands suggests that this increase will be limited by biogeographical constraints. Long-term harmonised monitoring across the circumpolar region is necessary to detect such changes to diversity and inform science-based management.</p

Neuroendocrine–immune disequilibrium and endometriosis: an interdisciplinary approach

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

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 historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições 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 biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema

Decoupling Measurements and Processes: On the Epiphenomenon Debate Surrounding Brain Oscillations in Field Potentials

Various theories in neuroscience maintain that brain oscillations have an important role in neuronal computation, but opposing views claim that these macroscale dynamics are “exhaust fumes” of more relevant processes. Here, we argue that the question of whether oscillations are epiphenomenal is ill-defined and cannot be productively resolved without further refinement. Toward that end, we outline a conceptual framework that clarifies the dispute along two axes: first, we introduce a distinction between measurement and process to categorize the theoretical status of electrophysiology terms such as local field potentials and oscillations. Second, we consider the relationships between these disambiguated terms, evaluating based on experimental and computational evidence whether there exist causal or inferentially useful links between them. This decomposes the question of epiphenomenalism into a set of empirically tractable alternatives. Finally, we demarcate oscillations as a conceptually distinct entity where either processes or measurements exhibit periodic behavior, and we suggest that oscillatory processes orchestrate neural computation by implementing a temporal, spatial, and frequency syntax. Overall, our reframed evaluation supports the view that electric fields—oscillating or not—are causally relevant, and that their associated signals are informative. More broadly, we offer a vocabulary and starting point for scientific exchanges on the role and utility of brain signals and the biological processes they capture

The problem-ladenness of theory

The cognitive sciences are facing questions of how to select from competing theories, or develop those that best suit their current needs. However, traditional accounts of theoretical virtues, focused on their epistemic justification, have not yet proven informative to theory development in these fields. We advance a problem-centric, or pragmatic, account by which theoretical virtues are heuristics we use to estimate the degree to which a theory increases the problem-solving efficacy of a field's body of knowledge. From this perspective, what are traditionally considered epistemic virtues can be couched in terms of their coverage of problems in a field's domain, or problem-space, and additional virtues come to light that reflect a theory’s ability to facilitate its use by problem-having agents and its context in a societally-embedded scientific system. This approach helps us understand why the different needs of different fields result in different kinds of theories, and allows us to formulate the challenges facing cognitive science in terms that we hope will facilitate their resolution through further theoretical development