- Overcoming obstacles to integrated response among incongruent organizations

2013 ◽  
pp. 474-499
Keyword(s):  
Integrated Response

CHANGES IN BLOOD PROTEOME OF COSMONAUTS WITH MICRO- AND MACROVASCULAR INJURIES DUE TO G-LOADS AT THE FINAL STAGE OF LONG-DURATION SPACE MISSIONS

2020 ◽  
Vol 54 (5) ◽  
pp. 5-14
Author(s):  
L.Kh. Pastushkova ◽  
◽  
K.S. Kireev ◽  
I.M. Larina ◽  
◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Soft Tissues ◽  
Blood Rheology ◽  
Landing Site ◽  
Space Missions ◽  
Vascular Injuries ◽  
New Approach ◽  
Long Duration ◽  
Integrated Response

The integrated response of the human proteome to re-entry g-loads following long-term space missions was studied in 13 male cosmonauts at the age of 44 ± 6 years. Examination at the landing site discovered local petechial hemorrhages into soft tissues of the back and lower legs. The paper presents a new approach to evaluation of petechia and soft tissue hemorrhages in cosmonauts on return to Earth. Proteomic analysis was performed with the use of LC-MS. Bioinformation analysis was made using Perseus, PubMed, Uniprot and ANDSystem software. Nine out of 19 significantly different (p < 0.05) proteins were related to vascular injuries directly. We described proteins with a primarily protecting effect against endothelial cells apoptosis and augmentation of vascular permeability, proteins that are responsible for blood rheology and proteins antagonistic to the main triggers of ischeamia-reperfusion injuries of the lungs, liver and other parenchymal organs.

scholarly journals TRAF6-IRF5 kinetics, TRIF, and biophysical factors drive synergistic innate responses to particle-mediated MPLA-CpG co-presentation

2021 ◽  
Vol 7 (3) ◽  
pp. eabd4235
Author(s):  
P. Pradhan ◽  
R. Toy ◽  
N. Jhita ◽  
A. Atalis ◽  
B. Pandey ◽  
...  
Keyword(s):  
Immune Responses ◽  
Molecular Mechanisms ◽  
Lipid A ◽  
Critical Role ◽  
Mouse Bone Marrow ◽  
Biophysical Properties ◽  
Gm Csf ◽  
Monophosphoryl Lipid A ◽  
Integrated Response ◽  
Particulate Carriers

Innate immune responses to pathogens are driven by co-presentation of multiple pathogen-associated molecular patterns (PAMPs). Combinations of PAMPs can trigger synergistic immune responses, but the underlying molecular mechanisms of synergy are poorly understood. Here, we used synthetic particulate carriers co-loaded with monophosphoryl lipid A (MPLA) and CpG as pathogen-like particles (PLPs) to dissect the signaling pathways responsible for dual adjuvant immune responses. PLP-based co-delivery of MPLA and CpG to GM-CSF–driven mouse bone marrow–derived antigen-presenting cells (BM-APCs) elicited synergistic interferon-β (IFN-β) and interleukin-12p70 (IL-12p70) responses, which were strongly influenced by the biophysical properties of PLPs. Mechanistically, we found that MyD88 and interferon regulatory factor 5 (IRF5) were necessary for IFN-β and IL-12p70 production, while TRIF signaling was required for the synergistic response. Both the kinetics and magnitude of downstream TRAF6 and IRF5 signaling drove the synergy. These results identify the key mechanisms of synergistic Toll-like receptor 4 (TLR4)–TLR9 co-signaling in mouse BM-APCs and underscore the critical role of signaling kinetics and biophysical properties on the integrated response to combination adjuvants.

scholarly journals Cell adaptive response to extracellular matrix density is controlled by ICAP-1–dependent β1-integrin affinity

2008 ◽  
Vol 180 (2) ◽  
pp. 427-441 ◽  
Author(s):  
Angélique Millon-Frémillon ◽  
Daniel Bouvard ◽  
Alexei Grichine ◽  
Sandra Manet-Dupé ◽  
Marc R. Block ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Β1 Integrin ◽  
Embryonic Fibroblasts ◽  
Matrix Surface ◽  
Extracellular Microenvironment ◽  
And Migration ◽  
Integrated Response ◽  
Insight Into

Cell migration is an integrated process requiring the continuous coordinated assembly and disassembly of adhesion structures. How cells orchestrate adhesion turnover is only partially understood. We provide evidence for a novel mechanistic insight into focal adhesion (FA) dynamics by demonstrating that integrin cytoplasmic domain–associated protein 1 (ICAP-1) slows down FA assembly. Live cell imaging, which was performed in both Icap-1–deficient mouse embryonic fibroblasts and cells expressing active β1 integrin, shows that the integrin high affinity state favored by talin is antagonistically controlled by ICAP-1. This affinity switch results in modulation in the speed of FA assembly and, consequently, of cell spreading and migration. Unexpectedly, the ICAP-1–dependent decrease in integrin affinity allows cell sensing of matrix surface density, suggesting that integrin conformational changes are important in mechanotransduction. Our results clarify the function of ICAP-1 in cell adhesion and highlight the central role it plays in the cell's integrated response to the extracellular microenvironment.

scholarly journals On the Relationship between Teleconnections and Taiwan's Streamflow: Evidence of Climate Regime Shift and Implications for Seasonal Forecasting

2016 ◽  
Author(s):  
Chia-Jeng Chen ◽  
Tsung-Yu Lee
Keyword(s):  
Large Scale ◽  
Critical Role ◽  
Phase Relationship ◽  
Temporal Variations ◽  
Pacific Basin ◽  
Climate Regime ◽  
Quasi Biennial Oscillation ◽  
Teleconnection Patterns ◽  
Integrated Response ◽  
The Relationship

Abstract. Interannual variations of catchment streamflow represent an integrated response to anomalies in regional moisture transport and atmospheric circulations, ultimately linked to large-scale climate oscillations. This study investigates the relationship between Taiwan's long-term summertime (July to September, JAS) streamflow and manifold teleconnection patterns. Lagged correlation analysis is conducted to calculate how JAS streamflow data derived at 28 upstream and 13 downstream gauges in Taiwan correlate with 14 teleconnection indices in the concurrent or preceding seasons. Out of the many indices, the West-Pacific and Pacific-Japan (PJ) patterns, both of which play a critical role in determining cyclonic activity in the western North Pacific basin, exhibit the highest concurrent correlations (most significant r = 0.48) with the JAS flows in Taiwan. At a one-month lead time, on the other hand, the Quasi-Biennial Oscillation significantly correlate with the JAS flows (most significant r = −0.66), indicating some forecasting utility. By further examining the correlation results using a 20-year moving window, peculiar temporal variations and possible climate regime shifts (CRS) can be revealed. To identify suspicious, abrupt changes in the correlation, a CRS test is employed. The late 1970s and 1990s are identified as two significant change points, and during the intermediate period, a marked in-phase relationship (r ~ 0.9) between Taiwan's streamflow and the PJ index is observed. It is verified that the two shifts are in concordance with the alteration of large-scale circulations in the Pacific basin. Discussion about the changes in pattern correlation and composite maps before and after the change point is carried out, and our results suggest that empirical forecasting techniques should take into account the effect of CRS on predictor screening.

scholarly journals Policy integration, problem-solving, and the coronavirus disease crisis: lessons for policy design

2022 ◽  
Author(s):  
Martino Maggetti ◽  
Philipp Trein
Keyword(s):  
Problem Solving ◽  
Policy Design ◽  
Policy Instruments ◽  
Policy Integration ◽  
Catching Up ◽  
The World ◽  
Integration Problem ◽  
The One ◽  
Integrated Response ◽  
Crisis Responses

Abstract The coronavirus disease pandemic has exposed differences in the capacity of governments around the world to integrate and coordinate different policy instruments into a coherent response. In this article, we conceptualize and empirically examine policy integration in responses to the coronavirus disease crisis in 35 countries. We then discuss how the interplay between restrictions, health protection, and economic policy has been articulated between, on the one hand, a policy design based on the complementarity of pro-public health and pro-economy measures, implying an integrated response, and, on the other, a policy design based on the perception of an inherent trade-off between the two. Finally, we discuss three implications from our analysis of policy integration against the coronavirus disease crisis for the post-COVID state: (a) the normalization and adaptation of integrated crisis responses; (b) the possible acceleration and “catching up” of problem-solving capacity as governments may use the crisis as an instance to put into place new social policies; and (c) policy integration as an accelerator of policy complexity and resistance against technocracy in the post-COVID state.

scholarly journals Integrated response of antioxidant biomarkers in the liver and white muscle of European hake (Merluccius merluccius L.) females from the Adriatic sea with respect to environmental influences

2018 ◽  
Vol 70 (1) ◽  
pp. 205-214 ◽  
Author(s):  
Sladjan Pavlovic ◽  
Slavica Borkovic-Mitic ◽  
Tijana Radovanovic ◽  
Branka Gavrilovic ◽  
Svetlana Despotovic ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
White Muscle ◽  
Adriatic Sea ◽  
Principal Component ◽  
Seasonal Effects ◽  
Merluccius Merluccius ◽  
Biomarker Response ◽  
Antioxidant Defense Enzymes ◽  
Integrated Response ◽  
European Hake

We investigated the integrated response of antioxidant defense enzymes (total superoxide dismutase (TotSOD), manganese-containing superoxide dismutase (MnSOD), copper-zinc-containing superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR) and phase II biotransformation enzyme, glutathione- S-transferase (GST)) in the liver and white muscle of females of European hake (Merluccius merluccius L.) from the Adriatic Sea (Montenegro) in winter and spring. The activity of GSH-Px in the liver was significantly increased, while GST activity was decreased in spring compared to the winter. In white muscle, the activities of TotSOD and CuZnSOD were increased, while the activities of MnSOD, CAT, GSH-Px, GR and GST were decreased in spring when compared to the matching values in winter. The activities of TotSOD and CuZnSOD in winter were markedly lower in the muscle than in the liver, while the activity of MnSOD in the muscle was higher when compared to the liver. Principal component analysis (PCA) revealed clear separation of the investigated antioxidant biomarkers between tissues and seasons, while the integrated biomarker response (IBR) showed that the most intensive antioxidant biomarker response was in the liver in spring. Star plots of IBR showed a dominant contribution of glutathione-dependent biomarkers (GSH-Px, GR and GST) and CAT in both tissues and seasons with respect to SOD isoenzymes. All enzyme activities (except MnSOD) were greater in the liver in comparison to the white muscle. Our results show that the liver possesses a greater capacity to establish and maintain homeostasis under changing environmental conditions in winter and spring. At the same time, seasonal effects are more pronounced in muscle tissue.

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