Immunopathogenic mechanisms of Coronary Artery Disease and plaque destabilization

Inflammation seems to play a role in both the chronic atherosclerotic process as well as in plaque destabilization, leading to the development of acute coronary syndromes (ACS). The aim of this study was to further investigate the immunopathogenic mechanisms in patients with coronary artery disease (CAD), primarily focusing on i) the pathogenic role of chemokines, ii) platelet-mediated inflammation, and iii) the pathogenic role of activin A as a potential “new” anti-inflammatory mediator in this process. We found that platelets upon activation released the inflammatory cytokine LIGHT, a member of the TNF superfamiliy, and that platelet-derived LIGHT could promote endothelial cell activation, potentially contributing to vascular inflammation in atherosclerotic disorders. The traditionally platelet-derived chemokine NAP-2 was also produced by peripheral mononuclear cells (PBMC), and we found that NAP-2 has the potential to induce an inflammatory response within the atherosclerotic plaque involving interaction between platelets, leukocytes and endothelial cells. By its ability to promote leukocyte activation as well as expression of chemokines and adhesion molecules within the vessel wall, such a NAP-2-driven inflammation could ultimately lead to plaque rupture and ACS. CAD patients had raised levels of the CXC chemokine CXCL16, with significantly down-regulatory effects of statins. Our in vitro experiments, showing potential inflammatory and matrix degrading properties of CXCL16, indicate that soluble CXCL16 is not only a marker, but also a mediator of inflammation with particularly enhancing effects in CAD patients. We also showed abnormal regulation of the homeostatic chemokines CCL19 and CCL21 and their common receptor CCR7 in atherosclerosis with particularly disturbed expression in unstable and advanced clinical and experimental disease. By recruiting T cells and macrophages to the atherosclerotic lesions, by promoting inflammatory responses in T cells, and by inducing a matrix degrading, pro-thrombotic, and inflammatory phenotype in macrophages, these chemokines could contribute to atherogenesis and plaque destabilization. In contrast, activin A, which was found to be up-regulated in CAD patients, was shown to display anti-inflammatory properties on mononuclear cells, in particular in patients with unstable disease. Our findings illustrate the complex regulation of the inflammatory responses during atherogenesis and plaque destabilization. Further studies on these aspects could potentially lead to new treatment modalities in these disorders

Enhanced oligonucleotide–nanoparticle conjugate stability using thioctic acid modified oligonucleotides

Metallic nanoparticles of gold functionalized with oligonucleotides conventionally use a terminal thiol modification and have been used in a wide range of applications. Although readily available, the oligonucleotide–nanoparticle conjugates prepared in this way suffer from a lack of stability when exposed to a variety of small molecules or elevated temperatures. If silver is used in place of gold then this lack of stability is even more pronounced. In this study we report the synthesis of highly stabilized oligonucleotide–nanoparticle conjugates using a simple oligonucleotide modification. A modified solid support was used to generate 3′-thioctic acid modified oligonucleotides by treatment with an N-hydroxysuccimidyl ester of thioctic acid. Unusually, both gold and silver nanoparticles have been investigated in this study and show that these disulphide-modified oligonucleotide probes offer significant improvements in nanoparticle stability when treated with dithiothreitol (DTT) compared with monothiol analogues. This is a significant advance in oligonucleotide–nanoparticle conjugate stability and for the first time allows silver nanoparticles to be prepared that are more stable than standard gold-thiol functionalized nanoparticles. This opens up the possibility of using silver nanoparticles functionalized with oligonucleotides as an alternative to gold

Enhanced oligonucleotide–nanoparticle conjugate stability using thioctic acid modified oligonucleotides

Metallic nanoparticles of gold functionalized with oligonucleotides conventionally use a terminal thiol modification and have been used in a wide range of applications. Although readily available, the oligonucleotide–nanoparticle conjugates prepared in this way suffer from a lack of stability when exposed to a variety of small molecules or elevated temperatures. If silver is used in place of gold then this lack of stability is even more pronounced. In this study we report the synthesis of highly stabilized oligonucleotide–nanoparticle conjugates using a simple oligonucleotide modification. A modified solid support was used to generate 3′-thioctic acid modified oligonucleotides by treatment with an N-hydroxysuccimidyl ester of thioctic acid. Unusually, both gold and silver nanoparticles have been investigated in this study and show that these disulphide-modified oligonucleotide probes offer significant improvements in nanoparticle stability when treated with dithiothreitol (DTT) compared with monothiol analogues. This is a significant advance in oligonucleotide–nanoparticle conjugate stability and for the first time allows silver nanoparticles to be prepared that are more stable than standard gold-thiol functionalized nanoparticles. This opens up the possibility of using silver nanoparticles functionalized with oligonucleotides as an alternative to gold

Segmentation of roots in soil with U-Net

Demonstration of the feasibility of a U-Net based CNN system for segmenting images of roots in soil and for replacing the manual line-intersect method

Old Bulloch Personalities (Supplement to No. 6)

This supplement to Southern Folkways Journal Review: Number 6 contains three articles by Smith Callaway Banks on Civil War personalities Captain William W. Williams, J.S. Cone Camp, and Garrett Williams. These are followed by an interview by Scott Collins with Daisy Davis Trapnell about Portal City Cemetery and by a list of Statesboro High School graduates and faculty complied by Camilla Akins Lanier.https://digitalcommons.georgiasouthern.edu/bchs-pubs/1026/thumbnail.jp

A grounded theory of inspirational coach leadership

The purpose of this study was to develop a grounded theory of the process of inspirational coach leadership in sport. A Straussian grounded theory methodology was used. Semi‐structured interviews and focus groups were conducted with athletes (n = 22) and coaches (n = 15). Data were analyzed through a process of open and axial coding, and theoretical integration. Through the process of analysis, data were broken down into smaller units (concepts), relationships between concepts were identified, and a substantive grounded theory was developed. The grounded theory of inspirational coach leadership was built around the core category of “athlete(s) inspired through changed awareness of their capabilities.” The core category was underpinned by three categories: (a) establishment of mutual trust and respect with athletes, whereby coaches need to establish trust with athletes in order to inspire athletes; (b) conditions under which inspiration has the potential to occur, which highlighted that athletes are inspired in situations where they are vulnerable or ignorant regarding their potential; and (c) coach acts to change athlete's awareness of their capabilities, which denotes the specific behaviors coaches should display to inspire athletes in such conditions. The theory also highlights that a range of contextual factors relating to the coach, athletes, and performance‐environment interact to impact upon the process. The theory predicts that consistency between coach behavior and the conditions in which inspiration can occur will lead to athlete inspiration, but only if the coach has established a foundation of trust and respect with the athlete