Effect of the experimental technique onto R dependence of ΔKth

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Involvement of long non-coding RNAs in beta cell failure at the onset of type 1 diabetes in NOD mice.

AIMS/HYPOTHESIS: Exposure of pancreatic beta cells to cytokines released by islet-infiltrating immune cells induces alterations in gene expression, leading to impaired insulin secretion and apoptosis in the initial phases of type 1 diabetes. Long non-coding RNAs (lncRNAs) are a new class of transcripts participating in the development of many diseases. As little is known about their role in insulin-secreting cells, this study aimed to evaluate their contribution to beta cell dysfunction. METHODS: The expression of lncRNAs was determined by microarray in the MIN6 beta cell line exposed to proinflammatory cytokines. The changes induced by cytokines were further assessed by real-time PCR in islets of control and NOD mice. The involvement of selected lncRNAs modified by cytokines was assessed after their overexpression in MIN6 cells and primary islet cells. RESULTS: MIN6 cells were found to express a large number of lncRNAs, many of which were modified by cytokine treatment. The changes in the level of selected lncRNAs were confirmed in mouse islets and an increase in these lncRNAs was also seen in prediabetic NOD mice. Overexpression of these lncRNAs in MIN6 and mouse islet cells, either alone or in combination with cytokines, favoured beta cell apoptosis without affecting insulin production or secretion. Furthermore, overexpression of lncRNA-1 promoted nuclear translocation of nuclear factor of κ light polypeptide gene enhancer in B cells 1 (NF-κB). CONCLUSIONS/INTERPRETATION: Our study shows that lncRNAs are modulated during the development of type 1 diabetes in NOD mice, and that their overexpression sensitises beta cells to apoptosis, probably contributing to their failure during the initial phases of the disease

Evaluation of active learning implementation base d on t he "teaching style questionnaire" for teachers

授業におけるアクティブラーニングの実施度合いを測定するうえで、学生が実際にアクティブラーニングを実現できたかを測ることは極めて難しい。岡山大学では、教員に対して授業実施内容に関するアンケート（授業スタイルアンケート）を行い、その結果によりアクティブラーニング実施率を調査する試みが行われた。本稿では、この「授業スタイルアンケート」の実施概要とその分析結果について報告する

Experiments on crack propagation and threshold at defects in press-fits of railway axles

Fatigue strength under fretting fatigue is one of the open problems in the area of fatigue. In the case of railway wheel-axle press-fits, there are no records of recent failures because design rules are today based on making the shape of geometrical transitions the most stressed point. However, it is important to analyze correctly the acceptability of defects and micro-cracks at press-fits. In this paper, after a preliminary presentation of the results obtained by a new criterion for predicting the non-propagation of cracks under rolling contact fatigue conditions, a new series of experiments on full-scale axle press-fits containing artificial defects is presented and discussed. Results show the modified Dang Van criterion is adequate for describing the development of natural cracks and cracks from artificial defects. The latter, characterized by a depth of 250 350 m, are competitors of fretting cracks naturally developed from surface scars and surface damage

Crack Growth Studies in Railway Axles under Corrosion Fatigue: Full-scale Experiments and Model Validation

Abstract Crack initiation and growth in full scale railway axle in A1T mild steel have been studied, under three points rotating bending loading conditions and artificial rainwater as corrosive environment. A surface plastic replication technique has been used along with optical microscopy and Scanning Electron Microscopy to monitor the environment assisted fatigue at various stages.A modified Murtaza and Akid empirical model has been employed to predict the corrosion fatigue crack growth rates and a reasonable agreement has been found between experimental and calculated lifetime

Tillering Dynamics of \u3ci\u3ePanicum maximum\u3c/i\u3e Jacq. cv. Tanzania-1 After Grazing

Tillering dynamics and tiller dry matter weight from Tanzania grass (Panicum maximum cv. Tanzania-1) were evaluated in two post-grazing stubbles (High Post-grazing Stubble – HPS-3.6 t of DM/ha and Low Post-grazing Stubble – LPS-2.3 t of DM/ha). There was no difference between post-grazing stubbles for decapitated axillary and basal remainder and new axillary tillers. The LPS presented greater number of new basal tillers. The rate of appearance of new basal and axillary tillers decreased with time after grazing. There were differences between the treatments on tiller dry matter weight, and greater values were found in the high post-graze stubble

Role for inducible cAMP early repressor in promoting pancreatic beta cell dysfunction evoked by oxidative stress in human and rat islets

Aims/hypothesis: Pro-atherogenic and pro-oxidant, oxidised LDL trigger adverse effects on pancreatic beta cells, possibly contributing to diabetes progression. Because oxidised LDL diminish the expression of genes regulated by the inducible cAMP early repressor (ICER), we investigated the involvement of this transcription factor and of oxidative stress in beta cell failure elicited by oxidised LDL. Methods: Isolated human and rat islets, and insulin-secreting cells were cultured with human native or oxidised LDL or with hydrogen peroxide. The expression of genes was determined by quantitative real-time PCR and western blotting. Insulin secretion was monitored by EIA kit. Cell apoptosis was determined by scoring cells displaying pycnotic nuclei. Results: Exposure of beta cell lines and islets to oxidised LDL, but not to native LDL raised the abundance of ICER. Induction of this repressor by the modified LDL compromised the expression of important beta cell genes, including insulin and anti-apoptotic islet brain 1, as well as of genes coding for key components of the secretory machinery. This led to hampering of insulin production and secretion, and of cell survival. Silencing of this transcription factor by RNA interference restored the expression of its target genes and alleviated beta cell dysfunction and death triggered by oxidised LDL. Induction of ICER was stimulated by oxidative stress, whereas antioxidant treatment with N-acetylcysteine or HDL prevented the rise of ICER elicited by oxidised LDL and restored beta cell functions. Conclusions/interpretation: Induction of ICER links oxidative stress to beta cell failure caused by oxidised LDL and can be effectively abrogated by antioxidant treatmen

Human high-density lipoprotein particles prevent activation of the JNK pathway induced by human oxidised low-density lipoprotein particles in pancreatic beta cells

Aims/hypothesis: We explored the potential adverse effects of pro-atherogenic oxidised LDL-cholesterol particles on beta cell function. Materials and methods: Isolated human and rat islets and different insulin-secreting cell lines were incubated with human oxidised LDL with or without HDL particles. The insulin level was monitored by ELISA, real-time PCR and a rat insulin promoter construct linked to luciferase gene reporter. Cell apoptosis was determined by scoring cells displaying pycnotic nuclei. Results: Prolonged incubation with human oxidised LDL particles led to a reduction in preproinsulin expression levels, whereas the insulin level was preserved in the presence of native LDL-cholesterol. The loss of insulin production occurred at the transcriptional levels and was associated with an increase in activator protein-1 transcriptional activity. The rise in activator protein-1 activity resulted from activation of c-Jun N-terminal kinases (JNK, now known as mitogen-activated protein kinase 8 [MAPK8]) due to a subsequent decrease in islet-brain 1 (IB1; now known as MAPK8 interacting protein 1) levels. Consistent with the pro-apoptotic role of the JNK pathway, oxidised LDL also induced a twofold increase in the rate of beta cell apoptosis. Treatment of the cells with JNK inhibitor peptides or HDL countered the effects mediated by oxidised LDL. Conclusions/interpretation: These data provide strong evidence that oxidised LDL particles exert deleterious effects in the progression of beta cell failure in diabetes and that these effects can be countered by HDL particle

Dihydroquinidine versus disopyramide: Efficacy in patients with chronic stable ventricular ectopy

Dihydroquinidine (DQ) is contained in substantial amounts in quinidine salts, but its direct antiarrhythmic action has not been studied. The efficacy of oral DQ (300 mg t. i. d.) compared to disopyramide (D) (200 mg t.i.d.) was thus investigated using a double-blind crossover placebo-controlled protocol in 12 patients, aged 13 to 67 years, with chronic stable high frequency premature ventricular beats (PVB), defined as greater than 100 PVB/h during 48-72-h control Holter monitoring. The protocol included three 72-h treatment periods: DQ, D, and placebo at random. On days 2 and 3 of each period a 24-h Holter recording was carried out; drug blood levels were determined at peak (days 2 and 3) and trough time (day 3). No significant difference in the mean PVB/h was found between control (735 +/- 400) and placebo periods (564 +/- 388), or between the two Holter recordings of each period. Compared to placebo both DQ (106 +/- 113, p less than 0.005) and D (240 +/- 263, p less than 0.05) reduced the mean PVB/h, but the decrease was significantly higher with DQ (78 versus 53%, p less than 0.02). Nine patients (75%) on DQ and 5 (42%) on D had a greater than 70% decrease in mean PVB/h; complex PVBs were abolished in 3 of 6 patients on both treatments. On day 3, DQ plasma levels were 1.31 +/- 0.44 (peak) and 0.92 +/- 0.45 (trough) mg/l; D plasma levels were 2.88 +/- 0.64 (peak) and 2.02 +/- 0.31 (trough) mg/l; no significant difference was found between day 2 and day 3 samples.(ABSTRACT TRUNCATED AT 250 WORDS