scholarly journals Dominant role of αIIbβ3 in platelet interactions with cross-linked fibrin fragment D-dimer

2020 ◽  
Vol 4 (13) ◽  
pp. 2939-2949
Author(s):  
Lorena Buitrago ◽  
Hina Zafar ◽  
Yixiao Zhang ◽  
Jihong Li ◽  
Thomas Walz ◽  
...  

Abstract Although much is known about the interaction of fibrinogen with αIIbβ3, much less is known about the interaction of platelets with cross-linked fibrin. Fibrinogen residue Lys406 plays a vital role in the interaction of fibrinogen with αIIbβ3, but because it participates in fibrin cross-linking, it is not available for interacting with αIIbβ3. We studied the adhesion of platelets and HEK cells expressing normal and constitutively active αIIbβ3 to both immobilized fibrinogen and D-dimer, a proteolytic fragment of cross-linked fibrin, as well as platelet-mediated clot retraction. Nonactivated platelets and HEK cells expressing normal αIIbβ3 adhered to fibrinogen but not D-dimer, whereas activated platelets as well as HEK cells expressing activated αIIbβ3 both bound to D-dimer. Small-molecule antagonists of the αIIbβ3 RGD (Arg-Gly-Asp) binding pocket inhibited adhesion to D-dimer, and an Asp119Ala mutation that disrupts the β3 metal ion–dependent adhesion site inhibited αIIbβ3-mediated adhesion to D-dimer. D-dimer and a polyclonal antibody against D-dimer inhibited clot retraction. The monoclonal antibody (mAb) 10E5, directed at αIIb and a potent inhibitor of platelet interactions with fibrinogen, did not inhibit the interaction of activated platelets with D-dimer or clot retraction, whereas the mAb 7E3, directed at β3, inhibited both phenomena. We conclude that activated, but not nonactivated, αIIbβ3 mediates interactions between platelets and D-dimer, and by extrapolation, to cross-linked fibrin. Although the interaction of αIIbβ3 with D-dimer differs from that with fibrinogen, it probably involves contributions from regions on β3 that are close to, or that are affected by, changes in the RGD binding pocket.

2002 ◽  
Vol 87 (02) ◽  
pp. 187-193 ◽  
Author(s):  
Mansoor Sajid ◽  
George Stouffer

Summaryαvβ3 integrins play an important role in vascular healing. Vascular injury is a stimulus for expression of αvβ3 by vascular cells and, among other effects, αvβ3 integrins function in the adhesion of activated platelets to endothelium, white cell/endothelium interactions, plateletmediated thrombin generation, fibrin clot retraction by nucleated cells, smooth muscle cell (SMC) migration and proliferation, vascular cell apoptosis, and vascular remodeling. There are ten different animal models in which treatment with αvβ3 antagonists reduced the vascular response, including (neo)intima formation, after mechanical injury. These studies, along with mechanistic data derived from cell culture studies, provide compelling evidence that αvβ3 integrins are involved in vascular repair processes. The challenge is to develop a therapeutic agent that will prove effective in reducing restenosis in humans following percutaneous coronary intervention (PCI).


Nanomaterials ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 1229 ◽  
Author(s):  
Ungor ◽  
Dékány ◽  
Csapó

In this review, the presentation of the synthetic routes of plasmonic gold nanoparticles (Au NPs), fluorescent gold nanoclusters (Au NCs), as well as self-assembled Au-containing thiolated coordination polymers (Au CPs) was highlighted. We exclusively emphasize the gold products that are synthesized by the spontaneous interaction of tetrachloroaurate(III) ions (AuCl4¯) with bioligands using amine and thiolate derivatives, including mainly amino acids. The dominant role of the nature of the applied reducing molecules as well as the experimental conditions (concentration of the precursor metal ion, molar ratio of the AuCl4¯ ions and biomolecules; pH, temperature, etc.) of the syntheses on the size and structure-dependent optical properties of these gold nanohybrid materials have been summarized. While using the same reducing and stabilizing biomolecules, the main differences on the preparation conditions of Au NPs, Au NCs, and Au CPs have been interpreted and the reducing capabilities of various amino acids and thiolates have been compared. Moreover, various fabrication routes of thiol-stabilized plasmonic Au NPs, as well as fluorescent Au NCs and self-assembled Au CPs have been presented via the formation of –(Au(I)-SR)n– periodic structures as intermediates.


2013 ◽  
Vol 18 (1) ◽  
pp. 1-18 ◽  
Author(s):  
Robert J. Barth

Abstract Scientific findings have indicated that psychological and social factors are the driving forces behind most chronic benign pain presentations, especially in a claim context, and are relevant to at least three of the AMA Guides publications: AMA Guides to Evaluation of Disease and Injury Causation, AMA Guides to Work Ability and Return to Work, and AMA Guides to the Evaluation of Permanent Impairment. The author reviews and summarizes studies that have identified the dominant role of financial, psychological, and other non–general medicine factors in patients who report low back pain. For example, one meta-analysis found that compensation results in an increase in pain perception and a reduction in the ability to benefit from medical and psychological treatment. Other studies have found a correlation between the level of compensation and health outcomes (greater compensation is associated with worse outcomes), and legal systems that discourage compensation for pain produce better health outcomes. One study found that, among persons with carpal tunnel syndrome, claimants had worse outcomes than nonclaimants despite receiving more treatment; another examined the problematic relationship between complex regional pain syndrome (CRPS) and compensation and found that cases of CRPS are dominated by legal claims, a disparity that highlights the dominant role of compensation. Workers’ compensation claimants are almost never evaluated for personality disorders or mental illness. The article concludes with recommendations that evaluators can consider in individual cases.


2014 ◽  
Vol 4 (2) ◽  
pp. 113-121 ◽  
Author(s):  
Stephanie Chow ◽  
Stephen Yortsos ◽  
Najmedin Meshkati

This article focuses on a major human factors–related issue that includes the undeniable role of cultural factors and cockpit automation and their serious impact on flight crew performance, communication, and aviation safety. The report concentrates on the flight crew performance of the Boeing 777–Asiana Airlines Flight 214 accident, by exploring issues concerning mode confusion and autothrottle systems. It also further reviews the vital role of cultural factors in aviation safety and provides a brief overview of past, related accidents. Automation progressions have been created in an attempt to design an error-free flight deck. However, to do that, the pilot must still thoroughly understand every component of the flight deck – most importantly, the automation. Otherwise, if pilots are not completely competent in terms of their automation, the slightest errors can lead to fatal accidents. As seen in the case of Asiana Flight 214, even though engineering designs and pilot training have greatly evolved over the years, there are many cultural, design, and communication factors that affect pilot performance. It is concluded that aviation systems designers, in cooperation with pilots and regulatory bodies, should lead the strategic effort of systematically addressing the serious issues of cockpit automation, human factors, and cultural issues, including their interactions, which will certainly lead to better solutions for safer flights.


Author(s):  
Palky Mehta ◽  
H. L. Sharma

In the current scenario of Wireless Sensor Network (WSN), power consumption is the major issue associated with nodes in WSN. LEACH technique plays a vital role of clustering in WSN and reduces the energy usage effectively. But LEACH has its own limitation in order to search cluster head nodes which are randomly distributed over the network. In this paper, ERA-NFL- BA algorithm is being proposed for selects the cluster heads in WSN. This algorithm help in selection of cluster heads can freely transform from global search to local search. At the end, a comparison has been done with earlier researcher using protocol ERA-NFL, which clearly shown that proposed Algorithm is best suited and from comparison results that ERA-NFL-BA has given better performance.


Accurate pronunciation has a vital role in English language learning as it can help learners to avoid misunderstanding in communication. However, EFL learners in many contexts, especially at the University of Phan Thiet, still encounter many difficulties in pronouncing English correctly. Therefore, this study endeavors to explore English-majored students’ perceptions towards the role of pronunciation in English language learning and examine their pronunciation practicing strategies (PPS). It involved 155 English-majored students at the University of Phan Thiet who answered closed-ended questionnaires and 18 English-majored students who participated in semi-structured interviews. The findings revealed that students strongly believed in the important role of pronunciation in English language learning; however, they sometimes employed PPS for their pronunciation improvement. Furthermore, the results showed that participants tended to use naturalistic practicing strategies and formal practicing strategies with sounds, but they overlooked strategies such as asking for help and cooperating with peers. Such findings could contribute further to the understanding of how students perceive the role of pronunciation and their PPS use in the research’s context and other similar ones. Received 10th June 2019; Revised 12th March 2020; Accepted 12th April 2020


IIUC Studies ◽  
2020 ◽  
Vol 15 ◽  
pp. 33-46
Author(s):  
Kalim Ullah

Human beings are deeply related to land. Human beings take birth on land, live on land, die on land and mixes with land ultimately. As stated in the holy Quran: ‘We (Allah) created you (human beings) from the soil, we shall make you return to the soil and We shall call you back again from the soil’ (20:55). Human life is surrounded by soil i.e. land. So, land is a highly completed issue of human life involving economic, social, political, cultural and often religious systems. Land administration is thus a critical element and often a pre-condition for peaceful society and sustainable development. In administrating land, Khatian or record of rights plays a vital role to determine the rights and interests of the respective parties as supportive evidence. In this article, discussion is mainly made on the fact that Khatian or record of rights is not a document of title solely but it may be an evidence of title as well as possession. IIUC Studies Vol.15(0) December 2018: 33-46


2020 ◽  
Vol 40 (1) ◽  
pp. 1-16
Author(s):  
Vivienne Dunstan

McIntyre, in his seminal work on Scottish franchise courts, argues that these courts were in decline in this period, and of little relevance to their local population. 1 But was that really the case? This paper explores that question, using a particularly rich set of local court records. By analysing the functions and significance of one particular court it assesses the role of this one court within its local area, and considers whether it really was in decline at this time, or if it continued to perform a vital role in its local community. The period studied is the mid to late seventeenth century, a period of considerable upheaval in Scottish life, that has attracted considerable attention from scholars, though often less on the experiences of local communities and people.


2018 ◽  
Vol 52 (1) ◽  
pp. 50-59
Author(s):  
Silvia Barnová ◽  
Viola Tamášová

Abstract Introduction: A certain degree of stress is present in everyone’s life and young people are not an exception. Most of them show a certain degree of resilience and can cope with stressful situations without any difficulties, however there is a group of youth who live in toxic environments and need help. If there is a risk of failure due to the intensity of stressors; external formal and informal support have a great role to play as they have the potential to prevent negative developmental outcomes. Purpose: The authors’ intention was to make a review of available literature on the current issues of resilience research with a focus on the importance of protective factors in young people’s lives – especially when they are exposed to adversity. An emphasis is placed on the vital role of social support to individuals provided by schools as well as social services. Methods: In the presented literature review, multiple formal search methods including hand searching of key journals; electronic searching of journal databases and subject specific websites; reference scanning; and citation tracking were used. Conclusion: Individuals commonly demonstrate some level of resilience, yet most of them are able to deal with stressful situations without any harm. On the other hand, if the adversity is too high, the presence of social support provided by their social environment is important. In this context, good relationships in general and sufficient external protective factors provided by their social environment (schools, school psychologists, institutional social and health service providers) are important.


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