Human Milk Oligosaccharide 2′-Fucosyllactose Modulates Local Viral Immune Defense by Supporting the Regulatory Functions of Intestinal Epithelial and Immune Cells

Human milk contains bioactive components that provide protection against viral infections in early life. In particular, intestinal epithelial cells (IEC) have key regulatory roles in the prevention of enteric viral infections. Here we established an in vitro model to study the modulation of host responses against enteric viruses mimicked by poly I:C (pIC). The effects of 2′-fucosyllactose (2′FL), abundantly present in human milk, were studied on IEC and/or innate immune cells, and the subsequent functional response of the adaptive immune cells. IEC were pre-incubated with 2′FL and stimulated with naked or Lyovec™-complexed pIC (LV-pIC). Additionally, monocyte-derived dendritic cells (moDC) alone or in co-culture with IEC were stimulated with LV-pIC. Then, conditioned-moDC were co-cultured with naïve CD4⁺ T helper (Th)-cells. IEC stimulation with naked or LV-pIC promoted pro-inflammatory IL-8, CCL20, GROα and CXCL10 cytokine secretion. However, only exposure to LV-pIC additionally induced IFNβ, IFNλ1 and CCL5 secretion. Pre-incubation with 2′FL further increased pIC induced CCL20 secretion and LV-pIC induced CXCL10 secretion. LV-pIC-exposed IEC/moDC and moDC cultures showed increased secretion of IL-8, GROα, IFNλ1 and CXCL10, and in the presence of 2′FL galectin-4 and -9 were increased. The LV-pIC-exposed moDC showed a more pronounced secretion of CCL20, CXCL10 and CCL5. The moDC from IEC/moDC cultures did not drive T-cell development in moDC/T-cell cultures, while moDC directly exposed to LV-pIC secreted Th1 driving IL-12p70 and promoted IFNγ secretion by Th-cells. Hereby, a novel intestinal model was established to study mucosal host-defense upon a viral trigger. IEC may support intestinal homeostasis, regulating local viral defense which may be modulated by 2′FL. These results provide insights regarding the protective capacity of human milk components in early life.     

Upregulation of miR145 and miR126 in EVs from Renal Cells Undergoing EMT and Urine of Diabetic Nephropathy Patients

Simple SummaryDiabetic nephropathy is one of the most frequent complications of diabetes, resulting from diffuse damage to different kidney cells. The identification of subjects at risk is mandatory to prevent its development and provide appropriate therapies reducing the unmanageable evolution towards end-stage kidney disease. The aim of this work was to identify urinary-derived extracellular vesicles (EVs) miRNA cargo to be used as biomarker of kidney damage in diabetic patients. The miRNA profile was then correlated with the molecular mechanism associated with the glomerular and tubular damage using a diabetic-like model. In patients, miR145 and miR126 in urinary EVs increased together with albuminuria. MiR145 and miR126 increased in parallel in EVs from renal epithelial cells undergoing transition to a fibrotic mesenchymal phenotype. These data unveiled a role for miR126 and miR145 as the biomarkers of damage progression and proteinuria development in diabetic nephropathy. AbstractDiabetic nephropathy (DN) is a severe kidney-related complication of type 1 and type 2 diabetes and the most frequent cause of end-stage kidney disease. Extracellular vesicles (EVs) present in the urine mainly derive from the cells of the nephron, thus representing an interesting tool mirroring the kidney’s physiological state. In search of the biomarkers of disease progression, we here assessed a panel of urinary EV miRNAs previously related to DN in type 2 diabetic patients stratified based on proteinuria levels. We found that during DN progression, miR145 and miR126 specifically increased in urinary EVs from diabetic patients together with albuminuria. In vitro, miRNA modulation was assessed in a model of TGF-β1-induced glomerular damage within a three-dimensional perfusion system, as well as in a model of tubular damage induced by albumin and glucose overload. Both renal tubular cells and podocytes undergoing epithelial to mesenchymal transition released EVs containing increased miR145 and miR126 levels. At the same time, miR126 levels were reduced in EVs released by glomerular endothelial cells. This work highlights a modulation of miR126 and miR145 during the progression of kidney damage in diabetes as biomarkers of epithelial to mesenchymal transition.     

Contribution to the problem of tensile and bending-test method for SiC-fibre-reinforced glass

The Young's moduli of SiC-fibre-reinforced DURAN glass composites with different fibre concentrations obtained from tensile and three-point-bending tests were shown to be in good agreement, while the values of strength and bendover stress and strain were larger in the bending test than in the tensile test. It is assumed that this difference is mainly a consequence of the larger effectively stressed sample volume in the tensile-stress test, compared to the bending test, and it is a consequence of the shift of the neutral line in the bending test towards the compressive-stress region during the fracture process. The second consequence is the reason why the samples behave in a much more ductile way in the bending test and are brittle in the tensile test. The advantages and disadvantages of the two methods are discussed and demonstrated with special regard to the composites mentioned.     

Third-party attitudes and strain reactions to the threat of a labor strike.

The authors examined how dispute-related stressors predicted strain experienced by third parties (N = 270) and their perceptions of a potential strike by part-time faculty. Immediately preceding a strike deadline, the authors surveyed students on their support for the union, perceived fairness, perceived effects of the impending strike, and perceived control. The authors also measured perceptions regarding information about the strike and psychological strain. Students facing increased disruptions because of the potential strike had decreased perceived control over their own tasks and over the university policies, and they experienced higher strain. Having more information about the dispute was associated with increased perceived task and policy control but was unassociated with strain. Both task and policy control moderated the relationship between disruptions and strain. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cyclin A1 is predominantly expressed in hematological malignancies with myeloid differentiation

OBJECTIVE: To document the frequency of conduction defects and their influence on prognosis in a large series of patients with acute myocardial infarction who underwent coronary care during a period when thrombolytic therapy was in common usage. BACKGROUND: Conduction defects have been associated with an adverse prognosis following acute myocardial infarction, but there are few data on the incidence and outcome of conduction defects since the introduction of thrombolytic therapy. PATIENTS AND METHODS: The study group comprised 1225 consecutive patients with acute myocardial infarction treated in the coronary care unit from 1 January 1988 to 31 December 1994. Conduction defects were recorded prospectively and were classified as follows: complete atrioventricular node block associated with narrow complex escape rhythms; left or right bundle branch block; bifascicular block; complete heart block involving both bundle branches. RESULTS: Electrocardiographic data were available in 1220 patients. Complete atrioventricular node block occurred in 65 (5.3%), left and right bundle branch block in 29 (2.4%) and 44 (3.6%) bifascicular block in 36 (2.9%) and complete heart block involving both bundle branches in 20 (1.6%). The more advanced degrees of block in the bundle branches occurred more commonly in patients with diabetes, previous infarction. Q-wave infarction, anterior infarction and left ventricular failure. Survival analysis showed an increased short- and long-term cardiac mortality in patients with conduction defects, prognosis worsening as the severity of the conduction defect increased. CONCLUSION: Conduction defects complicated acute myocardial infarction in 16% of cases and had a graded impact on the short- and long-term prognosis, patients with advanced bundle branch involvement faring worst. The data showed a small decline in the rate of severe conduction defects compared with previous studies, possibly reflecting the beneficial effects of thrombolytic therapy on infarct size.     

Zur Kettenwachstumsgeschwindigkeit der intermittierenden Äthylenpolymerisation

A general method to determine the propagation rate constant of slow polyreactions is described. By this method it can be shown that the active species of the coordinative polyreaction of ethylene by the soluble ZIEGLER-NATTA-catalyst (C₅H₅)₂Ti(C₂H₅)Cl/Al(C₂H₅)Cl₂ is a very dynamic equilibrium product and therefore the propagation process of a growing species is continuously interrupted corresponding to its average lifetime. The results, up to now, indicate that the average lifetime of a growing species on given conditions is less than 2 seconds and the rate constant of the first insertion steps must be greater than 20 1/mol sec for toluene as solvent and at a temperature of 10°C.