Upregulation of the Coagulation Factor VII Gene during Glucose Deprivation Is Mediated by Activating Transcription Factor 4

Background: Constitutive production of blood coagulation proteins by hepatocytes is necessary for hemostasis. Stressful conditions trigger adaptive cellular responses and delay processing of most proteins, potentially affecting plasma levels of proteins secreted exclusively by hepatocytes. We examined the effect of glucose deprivation on expression of coagulation proteins by the human hepatoma cell line, HepG2. Methodology/Principal Findings: Expression of coagulation factor VII, which is required for initiation of blood coagulation, was elevated by glucose deprivation, while expression of other coagulation proteins decreased. Realtime PCR and ELISA demonstrated that the relative percentage expression +/− SD of steady-state F7 mRNA and secreted factor VII antigen were significantly increased (from 100+/−15% to 188+/−27% and 100+/−8.8% to 176.3+/−17.3% respectively, p<0.001) at 24 hr of treatment. The integrated stress response was induced, as indicated by upregulation of transcription factor ATF4 and of additional stress-responsive genes. Small interfering RNAs directed against ATF4 potently reduced basal F7 expression, and prevented F7 upregulation by glucose deprivation. The response of the endogenous F7 gene was replicated in reporter gene assays, which further indicated that ATF4 effects were mediated via interaction with an amino acid response element in the F7 promoter. Conclusions/Significance: Our data indicated that glucose deprivation enhanced F7 expression in a mechanism reliant on prior ATF4 upregulation primarily due to increased transcription from the ATF4 gene. Of five coagulation protein genes examined, only F7 was upregulated, suggesting that its functions may be important in a systemic response to glucose deprivation stress

The Meteoric Ni Layer in the Upper Atmosphere

The first global atmospheric model of Ni (WACCM-Ni) has been developed to understand recent observations of the mesospheric Ni layer by ground-based resonance lidars. The three components of the model are: the Whole Atmospheric Community Climate Model (WACCM6); a meteoric input function derived by coupling an astronomical model of dust sources in the solar system with a chemical meteoric ablation model; and a comprehensive set of neutral, ion-molecule, and photochemical reactions pertinent to the chemistry of Ni in the upper atmosphere. In order to achieve closure on the chemistry, the reaction kinetics of three important reactions were first studied using a fast flow tube with pulsed laser ablation of a Ni target, yielding k(NiO + O) = (4.6 ± 1.4) × 10−11, k(NiO + CO) = (3.0 ± 0.5) × 10−11, and k(NiO2 + O) = (2.5 ± 1.2) × 10−11 cm3 molecule−1 s−1 at 294 K. The photodissociation rate of NiOH was computed to be J(NiOH) = 0.02 s−1. WACCM-Ni simulates satisfactorily the observed neutral Ni layer peak height and width, and Ni+ measurements from rocket-borne mass spectrometry. The Ni layer is predicted to have a similar seasonal and latitudinal variation as the Fe layer, and its unusually broad bottom-side compared with Fe is caused by the relatively fast NiO + CO reaction. The quantum yield for photon emission from the Ni + O3 reaction, observed in the nightglow, is estimated to be between 6% and 40%. ©2020. The Authors

The political process of constructing a sustainable London Olympics sports development legacy

This study attempts to develop a research agenda for understanding the process of constructing a sustainable Olympic sports development legacy. The research uses a social constructivist perspective to examine the link between the 2012 London Olympic Games and sustainable sports development. The first part of the paper provides justification for the study of sport policy processes using a constructivist lens. This is followed by a section which critically unpacks sustainable sports development drawing on Mosse’s (1998) ideas of process-oriented research and Searle’s conceptualisation of the construction of social reality. Searle’s (1995) concepts of the assignment of function, collective intentionality, collective rules, and human capacity to cope with the environment are considered in relation to the events and discourses emerging from the legacy vision(s) associated with the 2012 London Olympic Games. The paper concludes by proposing a framework for engaging in process oriented research and highlights key elements, research questions, and methodological issues. The proposed constructivist approach can be used to inform policy, practice, and research on sustainable Olympic sports development legacy

Evolving a Neural Model of Insect Path Integration

Path integration is an important navigation strategy in many animal species. We use a genetic algorithm to evolve a novel neural model of path integration, based on input from cells that encode the heading of the agent in a manner comparable to the polarization-sensitive interneurons found in insects. The home vector is encoded as a population code across a circular array of cells that integrate this input. This code can be used to control return to the home position. We demonstrate the capabilities of the network under noisy conditions in simulation and on a robot

Hubs with Network Motifs Organize Modularity Dynamically in the Protein-Protein Interaction Network of Yeast

BACKGROUND: It has been recognized that modular organization pervades biological complexity. Based on network analysis, 'party hubs' and 'date hubs' were proposed to understand the basic principle of module organization of biomolecular networks. However, recent study on hubs has suggested that there is no clear evidence for coexistence of 'party hubs' and 'date hubs'. Thus, an open question has been raised as to whether or not 'party hubs' and 'date hubs' truly exist in yeast interactome. METHODOLOGY: In contrast to previous studies focusing on the partners of a hub or the individual proteins around the hub, our work aims to study the network motifs of a hub or interactions among individual proteins including the hub and its neighbors. Depending on the relationship between a hub's network motifs and protein complexes, we define two new types of hubs, 'motif party hubs' and 'motif date hubs', which have the same characteristics as the original 'party hubs' and 'date hubs' respectively. The network motifs of these two types of hubs display significantly different features in spatial distribution (or cellular localizations), co-expression in microarray data, controlling topological structure of network, and organizing modularity. CONCLUSION: By virtue of network motifs, we basically solved the open question about 'party hubs' and 'date hubs' which was raised by previous studies. Specifically, at the level of network motifs instead of individual proteins, we found two types of hubs, motif party hubs (mPHs) and motif date hubs (mDHs), whose network motifs display distinct characteristics on biological functions. In addition, in this paper we studied network motifs from a different viewpoint. That is, we show that a network motif should not be merely considered as an interaction pattern but be considered as an essential function unit in organizing modules of networks

Monotone and near-monotone biochemical networks

Monotone subsystems have appealing properties as components of larger networks, since they exhibit robust dynamical stability and predictability of responses to perturbations. This suggests that natural biological systems may have evolved to be, if not monotone, at least close to monotone in the sense of being decomposable into a “small” number of monotone components, In addition, recent research has shown that much insight can be attained from decomposing networks into monotone subsystems and the analysis of the resulting interconnections using tools from control theory. This paper provides an expository introduction to monotone systems and their interconnections, describing the basic concepts and some of the main mathematical results in a largely informal fashion

The making of English cricket cultures: Empire, globalization and (post) colonialism

The aim of this article is to understand how English cricket cultures have been made, negotiated and, ultimately, resisted in the context of (post) colonialism. I draw upon research undertaken with white and British Asian cricketers in Yorkshire to identify the place and significance of cricket within the everyday lives of British Asian communities. Over the last decade the number of British Asian cricketers progressing into the upper echelons of the game (mainly the English County Championship) has increased. Many within the game (mainly white people) have used these figures to argue that English cricket is now 'colour blind'. However, I argue that representation is not the equivalent to acceptance and integration, and present evidence to suggest that racial prejudice and discrimination, not to mention inaccurate and essentialized cultural stereotypes of British Asian cricketers, remain firmly and routinely embedded in aspects of the sport at all levels. I argue that the ability of British Asians to resist the hegemonic structures of white 'Englishness', by asserting their own distinctive post-colonial identities in cricket, is paramount to their everyday negotiations of power and racism. © 2011 Taylor & Francis

Exploring the Mode of Action of Bioactive Compounds by Microfluidic Transcriptional Profiling in Mycobacteria

10.1371/journal.pone.0069191PLoS ONE87-POLN

Response to Comment on “Plant diversity increases with the strength of negative density dependence at the global scale”

Hülsmann and Hartig suggest that ecological mechanisms other than specialized natural enemies or intraspecific competition contribute to our estimates of conspecific negative density dependence (CNDD). To address their concern, we show that our results are not the result of a methodological artifact and present a null-model analysis that demonstrates that our original findings—(i) stronger CNDD at tropical relative to temperate latitudes and (ii) a latitudinal shift in the relationship between CNDD and species abundance—persist even after controlling for other processes that might influence spatial relationships between adults and recruits