Circular RNAs in urine of kidney transplant patients with acute T Cell-mediated allograft rejection

BACKGROUND: Circular RNAs (circRNAs) have recently been described as novel noncoding regulators of gene expression. They are detectable in the blood of patients with acute kidney injury. We tested whether circRNAs were present in urine and could serve as new predictors of outcome in renal transplant patients with acute rejection. METHODS: A global circRNA expression analysis using RNA from urine of patients with acute T cell-mediated renal allograft rejection and control transplant patients was performed. Dysregulated circRNAs were confirmed in a cohort of 62 patients with acute rejection, 10 patients after successful antirejection therapy, 18 control transplant patients without rejection, and 13 stable transplant patients with urinary tract infection. RESULTS: A global screen revealed several circRNAs to be altered in urine of patients with acute rejection. Concentrations of 2 circRNAs including hsa_circ_0001334 and hsa_circ_0071475 were significantly increased. These were validated in the whole cohort of patients. hsa_circ_0001334 was upregulated in patients with acute rejection compared with controls. Concentrations of hsa_circ_0001334 normalized in patients with acute rejection following successful antirejection therapy. hsa_circ_0001334 was associated with higher decline in glomerular filtration rate 1 year after transplantation. CONCLUSIONS: CircRNA concentrations are significantly dysregulated in patients with acute rejection at subclinical time points. Urinary hsa_circ_0001334 is a novel biomarker of acute kidney rejection, identifying patients with acute rejection and predicting loss of kidney function

AttributeProfile Designer

Die Firma the i-engineers mit Sitz in Aarau ist ein Hersteller eines CMS mit Kunden im Bereich Gesundheitswesen, Industrie und der öffentlichen Verwaltung. Das von the i-engineers entwickelte Informationsverwaltungssystem i-engine verfügt sowohl über einen Client, der als .Net standalone Applikation realisiert ist, als auch über einen Client in Adobe Flex. Die Definitionen für die Dialoge werden in der Datenbank hinterlegt, woraus der jeweilige Client dynamisch zur Laufzeit die entsprechenden Dialoge erstellt. Im Moment werden solche Dialog-Definitionen mittels SQL1-Scripten in die Datenbank eingefügt und geändert. Zur kompakten Beschreibung dieser Dialog-Definitionen wurde von uns ein XML2 Dateiformat entwickelt, welches durch ein Schema definiert ist. So können bestehende Dokumente gegen dieses Schema geprüft werden um deren Gültigkeit zu testen. Der in dieser Arbeit entwickelte AttributeProfile Designer bietet die Möglichkeit, diese Dialog-Definitionen komfortabel zu erstellen und zu bearbeiten. Die Dialog-Definitionen werden im zuvor definierten XML Dateiformat gespeichert. Zur Verbesserung der Bedienbarkeit sind Funktionen wie das Verschieben und Ändern der Grösse von Objekten per Drag & Drop möglich. Zusätzlich können Objekte als Templates exportiert und später wieder verwendet werden. Dies erspart dem Benutzer viele repetitive Tätigkeiten. Durch die Templates kann die Applikation flexibel an sich ändernde Bedingungen wie etwa Änderungen der i-engine angepasst werden.Weiter wurdeWert auf eine einfache Erweiterbarkeit der Applikation gelegt, damit später weitere Funktionen einfach hinzugefügt werden können

Punktgenaue Lokalisierung mittels RFID

Die Firma Albis Technologies bietet mit ZOMOFI® ein System zur Lokalisierung von RFID Tags in Gebäuden an. Die zonenbasierte Version dieses Systems wurde an der HSR bereits im Rahmen diverser Arbeiten untersucht und schliesslich zum Besuchermonitoring in Museen eingesetzt. Albis hat nun dieses System um einen Algorithmus zur punktgenauen Lokalisierung der Tags erweitert. Im ersten Teil der vorliegenden BA soll dieses System an der HSR installiert und geprüft werden. Dabei soll insbesondere untersucht werden, wie genau und unter welchen Bedingungen die Tags lokalisiert werden können und was für Anwendungsszenarien für das System denkbar sind. Zusätzlich soll für dieses Anwendungsszenario eine geeignete Visualisierung implementiert werden. Da die erreichte Genauigkeit des Systems aber nicht zur retrospektiven Ermittlung des von einer Person zurückgelegten Weges ausreicht, werden im zweiten Teil der Arbeit zwei eigene Algorithmen entwickelt. Diese sollen durch verschiedene Arten der Kalibrierung des Systems die Lokalisierung verbessern. Auf diese Weise die Genauigkeit schliesslich um knapp 15% gesteigert werden. Dies gilt allerdings nur für statische Tags ohne Personen

Nouveaux composés antifongiques

patent submitter:Selmod GmbHThe present invention refers to a compound having the formula (I): R1–Z–C≡C–C≡C–R3 (I) and pharmaceutical compositions comprising the same that can be used in prevention, treatment and alleviation of a fungal infection. The instant compounds and pharmaceutical compositions are particularly useful in treating, preventing and alleviating fungal infections caused by Candida fungi and Aspergillus fungi

Opportunities and limitations of milk mid-infrared spectra-based estimation of acetone and β-hydroxybutyrate for the prediction of metabolic stress and ketosis in dairy cows.

Subclinical (SCK) and clinical (CK) ketosis are metabolic disorders responsible for big losses in dairy production. Although Fourier-transform mid-infrared spectrometry (FTIR) to predict ketosis in cows exposed to great metabolic stress was studied extensively, little is known about its suitability in predicting hyperketonemia using individual samples, e.g. in small dairy herds or when only few animals are at risk of ketosis. The objective of the present research was to determine the applicability of milk metabolites predicted by FTIR spectrometry in the individual screening for ketosis. In experiment 1, blood and milk samples were taken every two weeks after calving from Holstein (n = 80), Brown Swiss (n = 72) and Swiss Fleckvieh (n = 58) cows. In experiment 2, cows diagnosed with CK (n = 474) and 420 samples with blood β-hydroxybutyrate [BHB] <1.0 mmol/l were used to investigate if CK could be detected by FTIR-predicted BHB and acetone from a preceding milk control. In experiment 3, correlations between data from an in farm automatic milk analyser and FTIR-predicted BHB and acetone from the monthly milk controls were evaluated. Hyperketonemia occurred in majority during the first eight weeks of lactation. Correlations between blood BHB and FTIR-predicted BHB and acetone were low (r = 0.37 and 0.12, respectively, P < 0.0001), as well as the percentage of true positive values (11.9 and 16.6%, respectively). No association of FTIR predicted ketone bodies with the interval of milk sampling relative to CK diagnosis was found. Data obtained from the automatic milk analyser were moderately correlated with the same day FTIR-predicted BHB analysis (r = 0.61). In conclusion, the low correlations with blood BHB and the small number of true positive samples discourage the use of milk mid-infrared spectrometry analyses as the only method to predict hyperketonemia at the individual cow level

Renal AAV2-Mediated Overexpression of Long Non-Coding RNA H19 Attenuates Ischemic Acute Kidney Injury Through Sponging of microRNA-30a-5p

BACKGROUND Renal ischemia-reperfusion (I/R) injury is a major cause of AKI. Noncoding RNAs are intricately involved in the pathophysiology of this form of AKI. Transcription of hypoxia-induced, long noncoding RNA H19, which shows high embryonic expression and is silenced in adults, is upregulated in renal I/R injury. METHODS Lentivirus-mediated overexpression, as well as antisense oligonucleotide-based silencing, modulated H19 in vitro. In vivo analyses used constitutive H19 knockout mice. In addition, renal vein injection of adeno-associated virus 2 (AAV2) carrying H19 caused overexpression in the kidney. Expression of H19 in kidney transplant patients with I/R injury was investigated. RESULTS H19 is upregulated in kidney biopsies of patients with AKI, in murine ischemic kidney tissue, and in cultured and ex vivo sorted hypoxic endothelial cells (ECs) and tubular epithelial cells (TECs). Transcription factors hypoxia-inducible factor 1-α, LHX8, and SPI1 activate H19 in ECs and TECs. H19 overexpression promotes angiogenesis in vitro and in vivo. In vivo, transient AAV2-mediated H19 overexpression significantly improved kidney function, reduced apoptosis, and reduced inflammation, as well as preserving capillary density and tubular epithelial integrity. Sponging of miR-30a-5p mediated the effects, which, in turn, led to target regulation of Dll4, ATG5, and Snai1. CONCLUSIONS H19 overexpression confers protection against renal injury by stimulating proangiogenic signaling. H19 overexpression may be a promising future therapeutic option in the treatment of patients with ischemic AKI

Altered glycosylation of IgG4 promotes lectin complement pathway activation in anti-PLA2R1–associated membranous nephropathy

Primary membranous nephropathy (pMN) is a leading cause of nephrotic syndrome in adults. In most cases, this autoimmune kidney disease is associated with autoantibodies against the M-type phospholipase A2 receptor (PLA2R1) expressed on kidney podocytes, but the mechanisms leading to glomerular damage remain elusive. Here, we developed a cell culture model using human podocytes and found that anti-PLA2R1–positive pMN patient sera or isolated IgG4, but not IgG4-depleted sera, induced proteolysis of the 2 essential podocyte proteins synaptopodin and NEPH1 in the presence of complement, resulting in perturbations of the podocyte cytoskeleton. Specific blockade of the lectin pathway prevented degradation of synaptopodin and NEPH1. Anti-PLA2R1 IgG4 directly bound mannose-binding lectin in a glycosylation-dependent manner. In a cohort of pMN patients, we identified increased levels of galactose-deficient IgG4, which correlated with anti-PLA2R1 titers and podocyte damage induced by patient sera. Assembly of the terminal C5b-9 complement complex and activation of the complement receptors C3aR1 or C5aR1 were required to induce proteolysis of synaptopodin and NEPH1 by 2 distinct proteolytic pathways mediated by cysteine and aspartic proteinases, respectively. Together, these results demonstrated a mechanism by which aberrantly glycosylated IgG4 activated the lectin pathway and induced podocyte injury in primary membranous nephropathy

Altered glycosylation of IgG4 promotes lectin complement pathway activation in anti-PLA2R1-associated membranous nephropathy

Primary membranous nephropathy (pMN) is a leading cause of nephrotic syndrome in adults. In most cases, this autoimmune kidney disease is associated with autoantibodies against the M-type phospholipase A2 receptor (PLA2R1) expressed on kidney podocytes, but the mechanisms leading to glomerular damage remain elusive. Here, we developed a cell culture model using human podocytes and found that anti-PLA2R1-positive pMN patient sera or isolated IgG4, but not IgG4-depleted sera, induced proteolysis of the 2 essential podocyte proteins synaptopodin and NEPH1 in the presence of complement, resulting in perturbations of the podocyte cytoskeleton. Specific blockade of the lectin pathway prevented degradation of synaptopodin and NEPH1. Anti-PLA2R1 IgG4 directly bound mannose-binding lectin in a glycosylation-dependent manner. In a cohort of pMN patients, we identified increased levels of galactose-deficient IgG4, which correlated with anti-PLA2R1 titers and podocyte damage induced by patient sera. Assembly of the terminal C5b-9 complement complex and activation of the complement receptors C3aR1 or C5aR1 were required to induce proteolysis of synaptopodin and NEPH1 by 2 distinct proteolytic pathways mediated by cysteine and aspartic proteinases, respectively. Together, these results demonstrated a mechanism by which aberrantly glycosylated IgG4 activated the lectin pathway and induced podocyte injury in primary membranous nephropathy. Keywords: Chronic kidney disease; Complement; Glycobiology; Immunology; Nephrology