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Gene-chip studies of adipogenesis-regulated microRNAs in mouse primary adipocytes and human obesity
Pernille Keller, Valentina Gburcik, Natasa Petrovic, Iain J Gallagher, Jan Nedergaard, Barbara Cannon, James A Timmons
BMC Endocrine Disorders , 2011, DOI: 10.1186/1472-6823-11-7
Abstract: Several models exist to study adipogenesis in vitro, of which the cell line 3T3-L1 is the most well known, albeit not the most physiologically appropriate. Thus, as an alternative, we produced EXIQON microarray of brown and white primary murine adipocytes (prior to and following differentiation) to yield global profiles of miRNAs.We found 65 miRNAs regulated during in vitro adipogenesis in primary adipocytes. We evaluated the similarity of our responses to those found in non-primary cell models, through literature data-mining. When comparing primary adipocyte profiles, with those of cell lines reported in the literature, we found a high degree of difference in 'adipogenesis' regulated miRNAs suggesting that the model systems may not be accurately representing adipogenesis. The expression of 10 adipogenesis-regulated miRNAs were studied using real-time qPCR and then we selected 5 miRNAs, that showed robust expression, were profiled in subcutaneous adipose tissue obtained from 20 humans with a range of body mass indices (BMI, range = 21-48, and all samples have U133+2 Affymetrix profiles provided). Of the miRNAs tested, mir-21 was robustly expressed in human adipose tissue and positively correlated with BMI (R2 = 0.49, p < 0.001).In conclusion, we provide a preliminary analysis of miRNAs associated with primary cell in vitro adipogenesis and demonstrate that the inflammation-associated miRNA, mir-21 is up-regulated in subcutaneous adipose tissue in human obesity. Further, we provide a novel transcriptomics database of EXIQON and Affymetrix adipocyte profiles to facilitate data mining.Obesity is a major global health problem linked to serious medical conditions including diabetes, heart disease, arthritis and cancer [1]. Adipose tissue is not only a main site of energy storage but also an important endocrine organ. It is a crucial regulator of energy balance and glucose homeostasis in mammals (reviewed in [2]). Imbalances in energy homeostasis cause obesity. Most of th
Coordination Processes in International Organisations: The EU at the International Labour Conference in 2005
Peter Nedergaard
European Integration Online Papers , 2008,
Abstract: The EU is not a member of the International Labour Organisation (ILO), but relatively elaborate EU coordination takes place anyway. This paper addresses two research questions: 1) How is it possible to evaluate the coordination of the EU in its specific observable configuration in the ILO?, and 2) To what outcome does this coordination lead and why? Based on an analysis of EU coordination before and during the International Labour Conference in 2005, and on a comparison with coordination processes of the IMEC group, it is found that the Commission and the Presidency act as twin-agents vis-à-vis their principals, the Member States. The Commission is the leading agent in the phase leading up to the Conference; the Presidency then takes over.On the one hand, due to the Treaty obligations and their interpretations by the Court of Justice, both the Presidency and the Commission are kept within tight limits by the principals. On the other hand, both before and during the Conference, the Member States accept the so-called discursive coordination of the Commission, which seems to be of great (but often neglected) importance. Owing to the organisational set-up in which coordination takes place, the EU is able to coordinate relatively elaborate agreements due to the strength of its coordination as far as professional or technical and political activities (excepting the ILO budget) are concerned. In other more clear-cut or 'simple' policy areas such as the ILO budget, the EU coordination is weak: this contrast with the strong coordination of the IMEC.
An siRNA-based method for efficient silencing of gene expression in mature brown adipocytes
Astrid L. Basse,Barbara Cannon,Jacob B. Hansen,Jan Nedergaard,M. Christine H. Petersen,Marie S. Isidor,Sally Winther
- , 2016, DOI: 10.1080/21623945.2015.1111972
Abstract: Brown adipose tissue is a promising therapeutic target for opposing obesity, glucose intolerance and insulin resistance. The ability to modulate gene expression in mature brown adipocytes is important to understand brown adipocyte function and delineate novel regulatory mechanisms of non-shivering thermogenesis. The aim of this study was to optimize a lipofection-based small interfering RNA (siRNA) transfection protocol for efficient silencing of gene expression in mature brown adipocytes. We determined that a critical parameter was to deliver the siRNA to mature adipocytes by reverse transfection, i.e. transfection of non-adherent cells. Using this protocol, we effectively knocked down both high- and low-abundance transcripts in a model of mature brown adipocytes (WT-1) as well as in primary mature mouse brown adipocytes. A functional consequence of the knockdown was confirmed by an attenuated increase in uncoupled respiration (thermogenesis) in response to β-adrenergic stimulation of mature WT-1 brown adipocytes transfected with uncoupling protein 1 siRNA. Efficient gene silencing was also obtained in various mouse and human white adipocyte models (3T3-L1, primary mouse white adipocytes, hMADS) with the ability to undergo “browning.” In summary, we report an easy and versatile reverse siRNA transfection protocol to achieve specific silencing of gene expression in various models of mature brown and browning-competent white adipocytes, including primary cells
From Talking Heads to Communicating Bodies: Cybersemiotics and Total Communication
Ole Nedergaard Thomsen
Entropy , 2010, DOI: 10.3390/e12030390
Abstract: Current linguistics is biased towards considering as object of scientific study only verbal language, i.e., ordinary language whose basic entities are words, sentences, and texts. By having this focus, the crucial non-verbal semiotic contributions from acts of bodily communication are left out of consideration. On the face of it, this is a strange situation, because, phenomenologically, when observing a communicating dyad, what appears to the senses is a multimodal semiotic display–the interactants produce acts of total communication, the linguistic part of which has in fact to be disentangled from the integral semiotic behavior. That a human being should in the first place be conceptualized as a ‘talking head’, rather than a ‘communicating body’, stems from at least four historically interrelated fountains: ancient Greek philosophy with its emphasis on logos as meaning both rational mind and verbal language/speech as well as with its rejection of rhetoric (including body language); Cartesian dualistic rationalism where the body was the animal, mechanistic part of a human being, unworthy for the Geisteswissenschaften; Saussure’s formal structuralism with its defocusing of the individual’s performance, parole, and its high focus on societal langue; and Chomskyan linguistics with its neglect of actual, also bodily, performance, and its total focus on an ideal mental grammatical computational competence. With the recent philosophy (‘in the flesh’) of the ‘embodied mind’, time has now come for integrating the (linguistic) head with the (other part of the communicating) body and seeing communication as total communication of the whole body. This means that the communicating mind is no longer restricted to its ‘rational’ aspects but has to be conceived full-scale as integrating also all kinds of ‘irrational’ factors, like emotions and motivations. Another, no less important, implication of the above is that an individual’s ‘language faculty’ is to be understood rather as a faculty of total communication–verbal and non-verbal semiotic behavior is an integrated, multi-modal whole of total communication performed by whole human organisms. Cybersemiotics offers itself here as the meta-theoretical, transdisciplinary framework within which this new paradigm of total communication can be developed.
Improved health-span and lifespan in mtDNA mutator mice treated with the mitochondrially targeted antioxidant SkQ1
Anne Hallden-Waldemarson,Antonina V. Pustovidko,Barbara Cannon,Daniel Edgar,Irina G. Shabalina,Jan Nedergaard,Lora E. Bakeeva,Mikhail Yu. Vyssokikh,Natalia Gibanova,Robert I. Csikasz,Valeria B. Vays,Vladimir P. Skulachev,Zinaida Rozhdestvenskaya
- , 2017, DOI: 10.18632/aging.101174
Abstract: MtDNA mutator mice exhibit marked features of premature aging. We find that these mice treated from age of ≈100 days with the mitochondria-targeted antioxidant SkQ1 showed a delayed appearance of traits of aging such as kyphosis, alopecia, lowering of body temperature, body weight loss, as well as ameliorated heart, kidney and liver pathologies. These effects of SkQ1 are suggested to be related to an alleviation of the effects of an enhanced reactive oxygen species (ROS) level in mtDNA mutator mice: the increased mitochondrial ROS released due to mitochondrial mutations probably interact with polyunsaturated fatty acids in cardiolipin, releasing malondialdehyde and 4-hydroxynonenal that form protein adducts and thus diminishes mitochondrial functions. SkQ1 counteracts this as it scavenges mitochondrial ROS. As the results, the normal mitochondrial ultrastructure is preserved in liver and heart; the phosphorylation capacity of skeletal muscle mitochondria as well as the thermogenic capacity of brown adipose tissue is also improved. The SkQ1-treated mice live significantly longer (335 versus 290 days). These data may be relevant in relation to treatment of mitochondrial diseases particularly and the process of aging in general
An algorithm for lifting points in a tropical variety
Anders Nedergaard Jensen,Hannah Markwig,Thomas Markwig
Mathematics , 2007,
Abstract: The aim of this paper is to give a constructive proof of one of the basic theorems of tropical geometry: given a point on a tropical variety (defined using initial ideals), there exists a Puiseux-valued ``lift'' of this point in the algebraic variety. This theorem is so fundamental because it justifies why a tropical variety (defined combinatorially using initial ideals) carries information about algebraic varieties: it is the image of an algebraic variety over the Puiseux series under the valuation map. We have implemented the ``lifting algorithm'' using Singular and Gfan if the base field are the rational numbers. As a byproduct we get an algorithm to compute the Puiseux expansion of a space curve singularity in (K^{n+1},0).
UCP1 Induction during Recruitment of Brown Adipocytes in White Adipose Tissue Is Dependent on Cyclooxygenase Activity
Lise Madsen,Lone M. Pedersen,Haldis Haukaas Lillefosse,Even Fj？re,Ingeborg Bronstad,Qin Hao,Rasmus K. Petersen,Philip Hallenborg,Tao Ma,Rita De Matteis,Pedro Araujo,Josep Mercader,M. Luisa Bonet,Jacob B. Hansen,Barbara Cannon,Jan Nedergaard,Jun Wang,Saverio Cinti,Peter Voshol,Stein Ove D？skeland,Karsten Kristiansen
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0011391
Abstract: The uncoupling protein 1 (UCP1) is a hallmark of brown adipocytes and pivotal for cold- and diet-induced thermogenesis.
Pathways for Genome Integrity in G2 Phase of the Cell Cycle
Arne Nedergaard Kousholt,Tobias Menzel,Claus Storgaard S？rensen
Biomolecules , 2012, DOI: 10.3390/biom2040579
Abstract: The maintenance of genome integrity is important for normal cellular functions, organism development and the prevention of diseases, such as cancer. Cellular pathways respond immediately to DNA breaks leading to the initiation of a multi-facetted DNA damage response, which leads to DNA repair and cell cycle arrest. Cell cycle checkpoints provide the cell time to complete replication and repair the DNA damage before it can continue to the next cell cycle phase. The G2/M checkpoint plays an especially important role in ensuring the propagation of error-free copies of the genome to each daughter cell. Here, we review recent progress in our understanding of DNA repair and checkpoint pathways in late S and G2 phases. This review will first describe the current understanding of normal cell cycle progression through G2 phase to mitosis. It will also discuss the DNA damage response including cell cycle checkpoint control and DNA double-strand break repair. Finally, we discuss the emerging concept that DNA repair pathways play a major role in the G2/M checkpoint pathway thereby blocking cell division as long as DNA lesions are present.
Correction: Kousholt, A.N. et al. Pathways for Genome Integrity in G2 Phase of the Cell Cycle. Biomolecules 2012, 2, 579-607
Arne Nedergaard Kousholt,Tobias Menzel,Claus Storgaard S？rensen
Biomolecules , 2013, DOI: 10.3390/biom3010072
Abstract: We have discovered an error in our paper published in Biomolecules [1], in Figure 1 on page 589. The protein names ATR and ATRIP have been swapped. A corrected version of the Figure 1 is provided below.
NATIONAL IDENTITY VERSUS EUROPEAN IDENTITY
Such, Jan
- , 2000,
Abstract: Sa？etak The author distinguishes four levels of integration: regional, national, European and global. The identity issue occurs at the national and European levels. National identities are subject to constant change, particularly in Europe, dominated by the processes of integration and globalization. Today, the new identities of European states emerge from “the vertical confrontation” (with the “higher order” identity), and not from the “horizontal relations” with other nations. Culture is essential in the development of a common European identity. The new European identity is not going to isolate Europe from the rest of the world. As a matter of fact, the European integration is but a single step in the direction of the global integration, and European identity a stage in achieving the fourth identity level
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