Plasma neutrophil gelatinase associated lipocalin (NGAL) is associated with kidney function in uraemic patients before and after kidney transplantation

<p>Abstract</p> <p>Background</p> <p>Neutrophil gelatinase associated lipocalin (NGAL) is a biomarker of kidney injury. We examined plasma levels of NGAL in a cohort of 57 kidney allograft recipients (Tx group, 39 ± 13 years), a uraemic group of 40 patients remaining on the waiting list (47 ± 11 years) and a control group of 14 healthy subjects matched for age, sex and body mass index (BMI). The kidney graft recipients were studied at baseline before transplantation and 3 and 12 months after transplantation and the uraemic group at baseline and after 12 months.</p> <p>Methods</p> <p>NGAL was measured using a validated in-house Time-Resolved Immuno-flourometric assay (TRIFMA). Repeated measurements differed by < 10% and mean values were used for statistical analyses. Spearman rank order correlation analysis and the Kruskal-Wallis non-parametric test were used to evaluate the association of NGAL concentrations with clinical parameters.</p> <p>Results</p> <p>Plasma NGAL levels before transplantation in the Tx and uraemic groups were significantly higher than in the healthy controls (1,251 μg/L, 1,478 μg/L vs. 163 μg/L, p < 0.0001). In the Tx group NGAL concentrations were associated with serum creatinine (R = 0.51, p < 0.0001), duration of end-stage renal failure (R = 0.41, p = 0.002) and leukocyte count (R = 0.29, p < 0.026). At 3 and 12 months plasma NGAL concentrations declined to 223 μg/L and 243 μg/L, respectively and were associated with homocysteine (R = 0.39, p = 0.0051 and R = 0.47, p = 0.0007).</p> <p>Conclusions</p> <p>Plasma NGAL is a novel marker of kidney function, which correlates to duration of end-stage renal failure (ESRD) and serum creatinine in uraemic patients awaiting kidney transplantation. Plasma NGAL is associated with homocysteine in transplanted patients. The prognostic value of these findings requires further studies.</p

Circulating Glucagon 1-61 Regulates Blood Glucose by Increasing Insulin Secretion and Hepatic Glucose Production

Glucagon is secreted from pancreatic a cells, and hypersecretion (hyperglucagonemia) contributes to diabetic hyperglycemia. Molecular heterogeneity in hyperglucagonemia is poorly investigated. By screening human plasma using high-resolution-proteomics, we identified several glucagon variants, among which proglucagon 1-61 (PG 1-61) appears to be the most abundant form. PG 1-61 is secreted in subjects with obesity, both before and after gastric bypass surgery, with protein and fat as the main drivers for secretion before surgery, but glucose after. Studies in hepatocytes and in b cells demonstrated that PG 1-61 dose-dependently increases levels of cAMP, through the glucagon receptor, and increases insulin secretion and protein levels of enzymes regulating glycogenolysis and gluconeogenesis. In rats, PG 1-61 increases blood glucose and plasma insulin and decreases plasma levels of amino acids in vivo. We conclude that glucagon variants, such as PG 1-61, may contribute to glucose regulation by stimulating hepatic glucose production and insulin secretion

CHOP Mediates Endoplasmic Reticulum Stress-Induced Apoptosis in Gimap5-Deficient T Cells

Gimap5 (GTPase of the immunity-associated protein 5) has been linked to the regulation of T cell survival, and polymorphisms in the human GIMAP5 gene associate with autoimmune disorders. The BioBreeding diabetes-prone (BBDP) rat has a mutation in the Gimap5 gene that leads to spontaneous apoptosis of peripheral T cells by an unknown mechanism. Because Gimap5 localizes to the endoplasmic reticulum (ER), we hypothesized that absence of functional Gimap5 protein initiates T cell death through disruptions in ER homeostasis. We observed increases in ER stress-associated chaperones in T cells but not thymocytes or B cells from Gimap5−/− BBDP rats. We then discovered that ER stress-induced apoptotic signaling through C/EBP-homologous protein (CHOP) occurs in Gimap5−/− T cells. Knockdown of CHOP by siRNA protected Gimap5−/− T cells from ER stress-induced apoptosis, thereby identifying a role for this cellular pathway in the T cell lymphopenia of the BBDP rat. These findings indicate a direct relationship between Gimap5 and the maintenance of ER homeostasis in the survival of T cells

Apoptosis of CD4+CD25high T Cells in Type 1 Diabetes May Be Partially Mediated by IL-2 Deprivation

from T1D subjects. in T1D may be caught up in a relatively deficient cytokine milieu. function in subjects predisposed to T1D

Foxp3 and Treg cells in HIV-1 infection and immuno-pathogenesis

FoxP3+CD4+CD25+ regulatory T (Treg) cells are implicated in a number of pathologic processes including elevated levels in cancers and infectious diseases, and reduced levels in autoimmune diseases. Treg cells are activated to modulate immune responses to avoid over-reactive immunity. However, conflicting findings are reported regarding relative levels of Treg cells during HIV-1 infection and disease progression. The role of Treg cells in HIV-1 diseases (aberrant immune activation) is poorly understood due to lack of a robust model. We summarize here the regulation and function of Foxp3 in Treg cells and in modulating HIV-1 replication. Based on recent findings from SIV/monkey and HIV/humanized mouse models, a model of the dual role of Treg cells in HIV-1 infection and immuno-pathogenesis is discussed

The Material Forms of Memory: A creative arts praxis examining family archive materiality and the performance of memory through installation art

This Master of Arts by Research investigates the role of new media in influencing familyarchive materiality and what effect this has on the performance of memory. The aim is to examine through creative arts praxis how installation art illuminates the participatory engagement of family archive materiality to mediate our mnemonic processes. The source materials for this project stem from my family archives dating from the early 1900s to 2013, and include photographs, 35mm slides, VHS tapes, audiotapes and personal items. The significance of this research lies in the creative outcomes that have occurred through the investigative and critical dialogues between artistic practices and theoretical discourses explored through exegetical writing. This hybrid approach to creative arts research allows for the negotiation of dialogues between myself as: researcher, creative practitioner and the subjective experiences that inform my art making practices (Barrett & Bolt, 2007; Gray, 1996). The installations that comprise this arts-based research reveal the participatory bodily engagement evoked from family archives across a range of media and how the materiality of theses archives influence our memories associated with family. A series of installations emerged, including—video works, photo-media sculptures created from over 3000 35mm slides, projections, new media, photography and audio. This exegesis draws parallels between relevant theoretical discourses, the work of visual artists Tacita Dean and Kutluğ Ataman, and my creative outcomes over the course of this candidature— spanning both studio experimentation and exhibited work. Creative outcomes of this research were exhibited over the course of my candidature, these exhibitions are— Becomings (2014); The Substance of Memory (2015) and the final exhibition Object Data Memory (2015). A reflexive studio inquiry spanning work-in-progress and exhibitions have fundamentally expounded the creative outcomes of this research. Central to this research is to investigate how new media has influenced the traditional role of the family archive. This exegesis aims to elucidate how a creative arts praxis integrating a multi-method research approach, in conjunction with reflexivity, has manifested a series of interactive and immersive installations that illuminate our bodily engagement with family archive materiality and what affect this has on the performance of memory.https://ro.ecu.edu.au/theses_ebooks/1004/thumbnail.jp