Functional Diversity and Structural Disorder in the Human Ubiquitination Pathway

The ubiquitin-proteasome system plays a central role in cellular regulation and protein quality control (PQC). The system is built as a pyramid of increasing complexity, with two E1 (ubiquitin activating), few dozen E2 (ubiquitin conjugating) and several hundred E3 (ubiquitin ligase) enzymes. By collecting and analyzing E3 sequences from the KEGG BRITE database and literature, we assembled a coherent dataset of 563 human E3s and analyzed their various physical features. We found an increase in structural disorder of the system with multiple disorder predictors (IUPred - E1: 5.97%, E2: 17.74%, E3: 20.03%). E3s that can bind E2 and substrate simultaneously (single subunit E3, ssE3) have significantly higher disorder (22.98%) than E3s in which E2 binding (multi RING-finger, mRF, 0.62%), scaffolding (6.01%) and substrate binding (adaptor/substrate recognition subunits, 17.33%) functions are separated. In ssE3s, the disorder was localized in the substrate/adaptor binding domains, whereas the E2-binding RING/HECT-domains were structured. To demonstrate the involvement of disorder in E3 function, we applied normal modes and molecular dynamics analyses to show how a disordered and highly flexible linker in human CBL (an E3 that acts as a regulator of several tyrosine kinase-mediated signalling pathways) facilitates long-range conformational changes bringing substrate and E2-binding domains towards each other and thus assisting in ubiquitin transfer. E3s with multiple interaction partners (as evidenced by data in STRING) also possess elevated levels of disorder (hubs, 22.90% vs. non-hubs, 18.36%). Furthermore, a search in PDB uncovered 21 distinct human E3 interactions, in 7 of which the disordered region of E3s undergoes induced folding (or mutual induced folding) in the presence of the partner. In conclusion, our data highlights the primary role of structural disorder in the functions of E3 ligases that manifests itself in the substrate/adaptor binding functions as well as the mechanism of ubiquitin transfer by long-range conformational transitions. © 2013 Bhowmick et al

Stratigraphy and sedimentation in Silurian flysch East of Millinocket, Maine

New England Intercollegiate Geological Conference Guidebook for field trips in The Greenville - Millinocket Regions, North Central Maine, October 7-9, 1983: Trip C-

Arnauld Charlotte, Véronique Breuil-Martínez y Érick Ponciano Alvarado, La Joyanca (La Libertad, Guatemala): antigua ciudad maya del noroeste del Petén, Centro Francés de Estudios Mexicanos y Centroamericanos (CEMCA), México D.F. / Asociación Tikal, Ciudad de Guatemala / Centro de Investigaciones Regionales de Mesoamérica (CIRMA), Antigua Guatemala, 2004, 138 p. + 16 pl. coul. + cédérom, bibl., gloss., index, ill., carte, plan, photos

This concise, thorough, and beautifully produced volume is one of the very few studies of a small site of the ancient Maya civilization of the Classic period (AD 300-900). It fills a major gap in the study of Classic Maya sites and is a volume that every Maya archaeologist should read. Maya archaeology, in general, has not been as theoretically and methodologically sophisticated as other subfields of archaeology and anthropology. Perhaps it is because of this traditionalist approach that exca..

Reporting on electoral violence in Nigerian news media: “Saying it as it is”?

While Nigeria has a vibrant press media landscape, freedom of the press is only rated as “partly free” by Freedom House, mostly due to political influences on reporting. Yet the extent to which these influences affect the quality of reporting remains insufficiently investigated. We address this gap by analyzing how three newspapers with different political affiliations report on conflict in the run-up to the 2015 elections. Our analyses indicate that biases in reporting are generally limited, and that while political pressures are real, they are most evident in editorial choices.The Institutions of Politics; Design, Workings, and implications ( do not use, ended 1-1-2020

How events enter (or not) data sets: the pitfalls and guidelines of using newspapers in the study of conflict

While conflict event data sets are increasingly used in contemporary conflict research, important concerns persist regarding the quality of the collected data. Such concerns are not necessarily new. Yet, because the methodological debate and evidence on potential errors remains scattered across different subdisciplines of social sciences, there is little consensus concerning proper reporting practices in codebooks, how best to deal with the different types of errors, and which types of errors should be prioritised. In this article, we introduce a new analytical framework—that is, the Total Event Error (TEE) framework—which aims to elucidate the methodological challenges and errors that may affect whether and how events are entered into conflict event data sets, drawing on different fields of study. Potential errors are diverse and may range from errors arising from the rationale of the media source (e.g., selection of certain types of events into the news) to errors occurring during the data collection process or the analysis phase. Based on the TEE framework, we propose a set of strategies to mitigate errors associated with the construction and use of conflict event data sets. We also identify a number of important avenues for future research concerning the methodology of creating conflict event data sets.Institutions, Decisions and Collective Behaviou

Managing diversity in Nigeria’s fourth republic national assembly: integrated parties versus ethno-regional balancing

Institutions, Decisions and Collective Behaviou

Global food security and food riots – an agent-based modelling approach

Due to negative consequences of climate change for agriculture and food production shocks affecting different areas of the world, the past two decades saw the conditions of global food security increasingly worsen. This has resulted in negative consequences for the world economy, partly causing international food price spikes and social upheavals. In this paper we present statistical findings along with a preliminary version of an original agent-based model called the Dawe Global Security Model that simulates the global food market and the political fragility of countries. The model simulates the effects of food insecurity on international food prices and how these, coupled with national political fragility and international food trade can, in turn, increase the probability of food riots in countries. The agents in the model are the 213 countries of the world whose characteristics reflect empirical data and the international trade of food is also simulated based on real trade partnerships and data. The model has been informed, calibrated and validated using real data and the results of these procedures are presented in the paper. To further test the model we also present the model’s forecasts for the near future in terms of food prices and incidence of food riots. The Dawe Global Security Model can be used to test scenarios on the evolution of shocks to global food production and analyse consequences for food riots. Further developments of the model can include national responses to food crises to investigate how countries can influence the spread of global food crises

Persistence of virus-specific immune responses in the central nervous system of mice after West Nile virus infection

<p>Abstract</p> <p>Background</p> <p>West Nile virus (WNV) persists in humans and several animal models. We previously demonstrated that WNV persists in the central nervous system (CNS) of mice for up to 6 months post-inoculation. We hypothesized that the CNS immune response is ineffective in clearing the virus.</p> <p>Results</p> <p>Immunocompetent, adult mice were inoculated subcutaneously with WNV, and the CNS immune response was examined at 1, 2, 4, 8, 12 and 16 weeks post-inoculation (wpi). Characterization of lymphocyte phenotypes in the CNS revealed elevation of CD19⁺B cells for 4 wpi, CD138 plasma cells at 12 wpi, and CD4⁺and CD8⁺T cells for at least 12 wpi. T cells recruited to the brain were activated, and regulatory T cells (Tregs) were present for at least 12 wpi. WNV-specific antibody secreting cells were detected in the brain from 2 to 16 wpi, and virus-specific CD8⁺T cells directed against an immunodominant WNV epitope were detected in the brain from 1 to 16 wpi. Furthermore, these WNV-specific immune responses occurred in mice with and without acute clinical disease.</p> <p>Conclusions</p> <p>Virus-specific immune cells persist in the CNS of mice after WNV infection for up to 16 wpi.</p

Nothing Lasts Forever: Environmental Discourses on the Collapse of Past Societies

The study of the collapse of past societies raises many questions for the theory and practice of archaeology. Interest in collapse extends as well into the natural sciences and environmental and sustainability policy. Despite a range of approaches to collapse, the predominant paradigm is environmental collapse, which I argue obscures recognition of the dynamic role of social processes that lie at the heart of human communities. These environmental discourses, together with confusion over terminology and the concepts of collapse, have created widespread aporia about collapse and resulted in the creation of mixed messages about complex historical and social processes

The silicon isotope composition of Ethmodiscus rexlaminated diatom mats from the tropical West Pacific: Implications for silicate cycling during the Last Glacial Maximum

The cause of massive blooms of Ethmodiscus rex laminated diatom mats (LDMs) in the eastern Philippine Sea (EPS) during the Last Glacial Maximum (LGM) remains uncertain. In order to better understand the mechanism of formation of E. rex LDMs from the perspective of dissolved silicon (DSi) utilization, we determined the silicon isotopic composition of single E. rex diatom frustules (δ30SiE. rex) from two sediment cores in the Parece Vela Basin of the EPS. In the study cores, δ30SiE. rex varies from −1.23‰ to −0.83‰ (average −1.04‰), a range that is atypical of marine diatom δ30Si and that corresponds to the lower limit of reported diatom δ30Si values of any age. A binary mixing model (upwelled silicon versus eolian silicon) accounting for silicon isotopic fractionation during DSi uptake by diatoms was constructed. The binary mixing model demonstrates that E. rex dominantly utilized DSi from eolian sources (i.e., Asian dust) with only minor contributions from upwelled seawater sources (i.e., advected from Subantarctic Mode Water, Antarctic Intermediate Water, or North Pacific Intermediate Water). E. rex utilized only ~24% of available DSi, indicating that surface waters of the EPS were eutrophic with respect to silicon during the LGM. Our results suggest that giant diatoms did not always use a buoyancy strategy to obtain nutrients from the deep nutrient pool, thus revising previously proposed models for the formation of E. rex LDMs