Loss of β-cell identity in diabetes: Significance of miR-7-mediated chromatin remodelling

Type 2 diabetes (T2D) affects 10% of the adult global population and is a multifactorial disease characterised by insulin resistance of peripheral organs. Insulin resistance results eventually in failure of pancreatic β-cells and subsequent apoptosis. Recent research revealed that β-cell dedifferentiation is contributing to decreasing their function in T2D. Dedifferentiated β-cells express atypical non-β-cell hormones, suggesting transdifferentiation into other cells. Our group previously showed that miR-7 levels are increased in T2D. Upregulation of miR-7a2 in β-cells of mice resulted in a diabetic phenotype and loss of key β-cell identity markers. The aims of this study were to 1) investigate if miR-7a2 triggers the dedifferentiation of β-cells, 2) identify messenger RNA (mRNA) targets of miR-7 which contribute to induce β-cell dedifferentiation in T2D, and 3) assess how miR-7 targets impact on the functional identity of mature β-cells. Our results showed that elevated miR-7a2 levels impair β-cell identity in mouse and human, accompanied by the occurrence of polyhormonal β-cells. Furthermore, we demonstrated that miR-7a2 is a regulator of the chromatin remodelling mSWI/SNF complexes, through repression of the catalytic ATPase subunit Brahma-related gene 1 (Brg1) both in vitro and in vivo. Additionally, we revealed that miR-7a2 represses the expression of BAF60A, a regulatory subunit of mSWI/SNF complexes. β-cell-specific miR-7a2 overexpression in mice resulted in the closure of chromatin around genes involved in maintaining β-cell identity. Those regions overlapped with binding sites of β-cell specific transcription factors (TF). Knockdown of Brg1 in β-cell lines and β-cell specific Brg1 deletion in mice resulted in the loss of β-cell identity as revealed by the downregulation of β-cell markers, reduction of pancreatic islet insulin protein content and an impairment in glucose stimulated insulin secretion (GSIS).Open Acces

A smart way to minimize test time for transformer dielectric measurements

Dielectric response measurements for the moisture and oil conductivity assessment of transformers are well understood, internationally accepted and growing in use. Of the two principal dielectric response methods, an AC method called Dielectric Frequency Response (DFR, also Frequency-Domain Spectroscopy, FDS) is preferred due to its robustness against noise. The time requirement of a DFR measurement is lengthy compared to that of other electrical test methods. An earlier approach to accelerate test time combined DC (time domain) and AC (frequency domain) test methods. This article discusses the limitations inherent to that approach and presents today’s multifrequency test solution that minimizes test time for DFR measurements without compromising accuracy

Senior Recital: Anna Von Ohlen

Kemp Recital HallApril 29, 2012Sunday Afternoon1:00 p.m

Herbivore Adaptations to Plant Cyanide Defenses

As plants are fixed to their habitat they produce specialized metabolites as chemical defenses to fight off herbivores. As an example, many plants produce cyanogenic glucosides and release toxic cyanide upon tissue damage (“cyanide bomb”). As a prerequisite for exploring cyanogenic plants as hosts, herbivores have evolved mechanisms to overcome cyanogenic defenses. Mammals metabolize cyanide to thiocyanate by rhodaneses. In arthropods, both rhodaneses and β-cyanoalanine synthases which transfer cyanide to cysteine contribute to cyanide detoxification. However, based on enzyme activity tests some arthropod species possess only one of these activities, and some possess both. Recently, cloning and characterization of first arthropod β-cyanoalanine synthases provided evidence for their involvement in cyanide detoxification. Phylogenetic analyses suggest that they have been recruited from microbial symbionts. Investigations with Zygaena filipendulae revealed that the avoidance of cyanide release is the primary mode of overcoming cyanide in this specialist. Some herbivores are able to sequester, de novo synthesize, and store cyanogenic glucosides for their defense and as nitrogen source. Thus, herbivores have evolved various mechanisms to counteract host plant cyanide defenses. These mechanisms are likely to have played a key role in the evolution of plant-herbivore interactions as well as in speciation and diversification of arthropods

Transcription of Ehrlichia chaffeensis genes is accomplished by RNA polymerase holoenzyme containing either sigma 32 or sigma 70

Citation: Liu, H., Ohlen, T. V., Cheng, C., Faburay, B., & Ganta, R. R. (2013). Transcription of Ehrlichia chaffeensis Genes Is Accomplished by RNA Polymerase Holoenzyme Containing either Sigma 32 or Sigma 70. PLOS ONE, 8(11), e81780. https://doi.org/10.1371/journal.pone.0081780Bacterial gene transcription is initiated by RNA polymerase containing a sigma factor. To understand gene regulation in Ehrlichia chaffeensis, an important tick-transmitted rickettsiae responsible for human monocytic ehrlichiosis, we initiated studies evaluating the transcriptional machinery of several genes of this organism. We mapped the transcription start sites of 10 genes and evaluated promoters of five genes (groE, dnaK, hup, p28-Omp14 and p28-Omp19 genes). We report here that the RNA polymerase binding elements of E. chaffeensis gene promoters are highly homologous for its only two transcription regulators, sigma 32 and sigma 70, and that gene expression is accomplished by either of the transcription regulators. RNA analysis revealed that although transcripts for both sigma 32 and sigma 70 are upregulated during the early replicative stage, their expression patterns remained similar for the entire replication cycle. We further present evidence demonstrating that the organism’s -35 motifs are essential to transcription initiations. The data suggest that E. chaffeensis gene regulation has evolved to support the organism’s growth, possibly to facilitate its intraphagosomal growth. Considering the limited availability of genetic tools, this study offers a novel alternative in defining gene regulation in E. chaffeensis and other related intracellular pathogens

Hospital incident command system (HICS) performance in Iran; decision making during disasters

<p>Abstract</p> <p>Background</p> <p>Hospitals are cornerstones for health care in a community and must continue to function in the face of a disaster. The Hospital Incident Command System (HICS) is a method by which the hospital operates when an emergency is declared. Hospitals are often ill equipped to evaluate the strengths and vulnerabilities of their own management systems before the occurrence of an actual disaster. The main objective of this study was to measure the decision making performance according to HICS job actions sheets using tabletop exercises.</p> <p>Methods</p> <p>This observational study was conducted between May 1st 2008 and August 31st 2009. Twenty three Iranian hospitals were included. A tabletop exercise was developed for each hospital which in turn was based on the highest probable risk. The job action sheets of the HICS were used as measurements of performance. Each indicator was considered as 1, 2 or 3 in accordance with the HICS. Fair performance was determined as < 40%; intermediate as 41-70%; high as 71-100% of the maximum score of 192. Descriptive statistics, T-test, and Univariate Analysis of Variance were used.</p> <p>Results</p> <p>None of the participating hospitals had a hospital disaster management plan. The performance according to HICS was intermediate for 83% (n = 19) of the participating hospitals. No hospital had a high level of performance. The performance level for the individual sections was intermediate or fair, except for the logistic and finance sections which demonstrated a higher level of performance. The public hospitals had overall higher performances than university hospitals (P = 0.04).</p> <p>Conclusions</p> <p>The decision making performance in the Iranian hospitals, as measured during table top exercises and using the indicators proposed by HICS was intermediate to poor. In addition, this study demonstrates that the HICS job action sheets can be used as a template for measuring the hospital response. Simulations can be used to assess preparedness, but the correlation with outcome remains to be studied.</p

Mittelfristige Ergebnisse der Bypasschirurgie und der stentoptimierten Angioplastie bei Patienten mit kritischer Extremitätenischämie und insulinpflichtigem Typ 2 Diabetes mellitus

Die periphere arterielle Verschlusskrankheit stellt bei Diabetikern eine häufige Komplikation mit schlechter Prognose dar. Im Stadium der kritischen Ischämie (Stadium III und IV nach Fontaine, bzw. 4, 5 und 6 nach Rutherford)  ist ein gefäßchirurgischer Eingriff unumgänglich.Um zu eruieren, welche Therapiemaßnahme, die offen chirurgische Bypass-Implantation oder die stentoptimierte Angioplastie, wurden die Daten von 136 Typ 2-Diabetiker mit einer kritischen Extremitätenischämie retrospektiv zwei Jahre nach der Intervention untersucht und die Ergebnisse der beiden Therapiemethoden miteinander verglichen.Sowohl die Bypass-Implantation als auch die stentoptimierte Angioplastie zeigten hinsichtlich der postoperativen Durchblutungssituation, Offenheitswahrscheinlichkeit und Amputationsrisiko ebenbürtige Ergebnisse.Somit scheint, nach den Ergebnissen dieser Studie, die Stent-PTA eine zumindest gleichwertige Therapieoption einer CLI bei Diabetikern zu sein

Musical Theatre Cabaret: Colleen Longo, Mezzo-Soprano; Justin Triezenberg, Piano and Tenor; Anna Von Ohlen, Bass; Kyle Johnson, Drums; February 13, 2010

Kemp Recital HallFebruary 13, 2010Friday Evening8:00 p.m