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Search Results: 1 - 10 of 227489 matches for " Lars R?nnstrand "
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Src-Like Adaptor Protein (SLAP) Binds to the Receptor Tyrosine Kinase Flt3 and Modulates Receptor Stability and Downstream Signaling
Julhash U. Kazi, Lars Rnnstrand
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0053509
Abstract: Fms-like tyrosine kinase 3 (Flt3) is an important growth factor receptor in hematopoiesis. Gain-of-function mutations of the receptor contribute to the transformation of acute myeloid leukemia (AML). Src-like adaptor protein (SLAP) is an interaction partner of the E3 ubiquitin ligase Cbl that can regulate receptor tyrosine kinases-mediated signal transduction. In this study, we analyzed the role of SLAP in signal transduction downstream of the type III receptor tyrosine kinase Flt3. The results show that upon ligand stimulation SLAP stably associates with Flt3 through multiple phosphotyrosine residues in Flt3. SLAP constitutively interacts with oncogenic Flt3-ITD and co-localizes with Flt3 near the cell membrane. This association initiates Cbl-dependent receptor ubiquitination and degradation. Depletion of SLAP expression by shRNA in Flt3-transfected Ba/F3 cells resulted in a weaker activation of FL-induced PI3K-Akt and MAPK signaling. Meta-analysis of microarray data from patient samples suggests that SLAP mRNA is differentially expressed in different cancers and its expression was significantly increased in patients carrying the Flt3-ITD mutation. Thus, our data suggest a novel role of SLAP in different cancers and in modulation of receptor tyrosine kinase signaling apart from its conventional role in regulation of receptor stability.
C-KIT Signaling Depends on Microphthalmia-Associated Transcription Factor for Effects on Cell Proliferation
Bengt Phung, Jianmin Sun, Alexander Schepsky, Eirikur Steingrimsson, Lars Rnnstrand
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0024064
Abstract: The development of melanocytes is regulated by the tyrosine kinase receptor c-KIT and the basic-helix-loop-helix-leucine zipper transcription factor Mitf. These essential melanocyte survival regulators are also well known oncogenic factors in malignant melanoma. Despite their importance, not much is known about the regulatory mechanisms and signaling pathways involved. In this study, we therefore sought to identify the signaling pathways and mechanisms involved in c-KIT mediated regulation of Mitf. We report that c-KIT stimulation leads to the activation of Mitf specifically through the c-KIT phosphorylation sites Y721 (PI3 kinase binding site), Y568 and Y570 (Src binding site). Our study not only confirms the involvement of Ras-Erk signaling pathway in the activation of Mitf, but also establishes that Src kinase binding to Y568 and Y570 of c-KIT is required. Using specific inhibitors we observe and verify that c-KIT induced activation of Mitf is dependent on PI3-, Akt-, Src-, p38- or Mek kinases. Moreover, the proliferative effect of c-KIT is dependent on Mitf in HEK293T cells. In contrast, c-KIT Y568F and Y721F mutants are less effective in driving cell proliferation, compared to wild type c-KIT. Our results reveal novel mechanisms by which c-KIT signaling regulates Mitf, with implications for understanding both melanocyte development and melanoma.
Potential role of IFNα in adult lupus
Lars R?nnblom
Arthritis Research & Therapy , 2010, DOI: 10.1186/ar2884
Abstract: Systemic lupus erythematosus, or lupus, is one of the most intriguing diseases due to its diverse clinical picture, variable course and in the single patient also its unpredictable outcome. The etiopathogenesis of lupus has been studied intensively for many years and the disease has long been regarded as the prototype autoimmune disease. The reason for this is that a large number of different autoantibodies are produced in lupus patients and that most, if not all, cells in the immune system seem to be involved in the disease process.The most prominent feature in lupus is an immune response to nucleic acid and associated proteins, which results in autoantibody production, immune complex (IC) formation and organ inflammation. In addition, most lupus patients display several signs of an increased IFNα production, which during the past years has attracted much interest regarding the possible role of this cytokine in the disease process. This interest has been further inspired by the observation that IFNα administration to individuals without any autoimmune condition can trigger the production of antinuclear autoantibodies, and occasionally also a lupus syndrome.In the present review, the possible reason(s) behind the ongoing IFNα production in lupus will be reviewed, as well as the role of IFNα in the etiopathogenesis and the clinical manifestations of the disease. The potential application in clinical practice of our present knowledge of the type I interferon system in lupus will also be discussed.The first described cytokine abnormality in lupus patients was an increased serum level of interferon [1], which subsequently was characterized as IFNα [2]. Early studies also demonstrated that lupus patients have increased levels of IFNα-induced proteins, such as 2',5'-adenylate synthetase [3] and MxA [4]. The latter report showed that >90% of lupus patients displayed increased expression of MxA, even if measurable serum IFNα levels could not be detected. Further studies sho
Small Size Hashes with Enhanced Security
Lars R Knudsen
International Journal of Network Security , 2006,
Abstract: This paper contains techniques for enhancing the strength of any cryptographic hash function. For an ``ideal'', traditional hash function with an m-bit result, the complexity of a collision attack is approximately 2^{m/2}. Here constructions are presented where collisions are harder to find.
How to Live with the Enemy: Understanding Tolerance to Parasites
Lars R?berg
PLOS Biology , 2014, DOI: 10.1371/journal.pbio.1001989
Abstract: How do we defend ourselves against pathogenic microbes and other parasites infecting us? Research on defence against parasites has traditionally focused on resistance—the ability to prevent infection or limit parasite replication. The genetics, physiology, and evolutionary ecology of such traits are now relatively well understood. During the last few years it has been realized that another, conceptually different type of defence also plays an important role in animal host–parasite interactions. This type of defence is called tolerance, and can be defined as the ability to limit the health effects of parasites without preventing infection or controlling parasite replication. Our understanding of the causes and consequences of variation in tolerance is, however, still rudimentary. Three recent studies shed light on these questions. In a study of HIV in humans, Regoes et al. show that an MHC class I gene affects not only resistance (as previously known) but also tolerance. In a study of voles, Jackson et al. identify a transcription factor mediating age differences in tolerance to macroparasites. Finally, Hayward et al. demonstrate that tolerance to intestinal parasites in sheep is under positive directional selection, but that most of the variation is environmentally induced rather than heritable. These studies increase our knowledge of the genetic and physiological sources of variation in tolerance, and how this variation affects Darwinian fitness. In addition, they illustrate different approaches to untangle tolerance from other factors determining the health effects of infectious disease.
Low-Level Laser on Hearing: Is There an Effect?
Jan Tunér,Lars Hode
ISRN Otolaryngology , 2013, DOI: 10.1155/2013/839256
Abstract:
Magnetism in Co$_{1-{\rm x}}$Fe$_{\rm x}$Sb$_{3}$ skutterudites from density functional theory
Mikael R?sander,Lars Bergqvist
Physics , 2015,
Abstract: We have investigated the electronic and magnetic properties of Co$_{1-{\rm x}}$Fe$_{\rm x}$Sb$_{3}$ skutterudites from density functional theory and Monte Carlo simulations. We find that above a certain threshold in the Fe concentration, somewhere between x=0.125 and x=0.25, Co$_{1-{\rm x}}$Fe$_{\rm x}$Sb$_{3}$ is ferromagnetic with an atomic moment which increases asymptotically towards about 1 $\mu_{B}$/Fe and a non-zero Curie temperature which reaches 70 K for FeSb$_{3}$. Ferromagnetism is favored due to a Stoner instability in the electronic structure, where a large density of states at the Fermi-level makes it favorable to form the ferromagnetic ground state.
Introductory course on $\ell$-adic sheaves and their ramification theory on curves
Lars Kindler,Kay Rülling
Mathematics , 2014,
Abstract: These are the (preliminary) notes accompanying 13 lectures given by the authors at the Clay Mathematics Institute Summer School 2014 in Madrid. The notes give an introduction into the theory of $\ell$-adic sheaves with emphasis on their ramification theory on curves.
Differences in the Defense Mechanism Technique modified (DMTm) between Depressive and Somatoform Disorder Patients  [PDF]
Lars Olsson
Open Journal of Depression (OJD) , 2015, DOI: 10.4236/ojd.2015.41001
Abstract: Differences in the Defense Mechanism Technique modified (DMTm), a percept-genetic tachistoscopic technique, between 56 patients with a main diagnosis of mild, moderate or severe unipolar depression and 42 with a main diagnosis of somatoform disorder were studied. As expected, the affect defenses of inhibition, introaggression and barrier isolation—all through their specified motive related to the depressive position of the affect positions model of the Andersson developmental and psychodynamic model of the mind—appeared more often with the depressive than the somatoform patients. Repression scored at the place of the threatening person in the DMTm pictures (Pp-repression) was more often found with the depressive patients, projected introaggression and no Pp-repression but repression scored at the place of the non-threatening person (H-repression) with the somatoform. In total less than four scorings of affect anxiety and affect defense, seen to indicate alexithymia, characterized the somatoform patients and those with mild depression. Denial through reversal II 3 and denial through reversal IV were common with the somatoform patients and those with severe depression. Denial was uncommon with mild depression. Denial, denial through reversal II 3 and denial through reversal IV increased the more severe the depression. The findings were interpreted according to the Andersson model.
On the Nature of Suicide—Suicide as a Multipurpose Behaviour Nested in the Human Mind—An Alternative View!  [PDF]
Lars Jacobsson
Open Journal of Psychiatry (OJPsych) , 2018, DOI: 10.4236/ojpsych.2018.82013
Abstract: Suicide is a universal human phenomenon and seems to be a multipurpose behaviour which occurs in a number of different situations that not necessarily have to do with mental distress/disorder. It might as well be a kind of defence of a threatened self-image or revenge or punishment or weapon in a struggle for something more important than the own life. Is there a suicidal virus or meme nested in the human mind? Maybe it is the mere idea of suicide as an alternative way of dealing with a number of human dilemmas that should be the focus of our suicide preventive efforts? Suicide ideas are common in most populations, but ideas are just ideas. It is when the ideas—the suicidal thoughts—are converted to actions that they become dangerous. The focus for our suicide preventive work should be to counteract a destructive use of suicidal ideation. So, the crucial question is thus: how do we do that?
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