| 1. |
- Bergman, Olle, 1978, et al.
(författare)
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Association between amygdala reactivity and a dopamine transporter gene polymorphism.
- 2014
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Essential for detection of relevant external stimuli and for fear processing, the amygdala is under modulatory influence of dopamine (DA). The DA transporter (DAT) is of fundamental importance for the regulation of DA transmission by mediating reuptake inactivation of extracellular DA. This study examined if a common functional variable number tandem repeat polymorphism in the 3' untranslated region of the DAT gene (SLC6A3) influences amygdala function during the processing of aversive emotional stimuli. Amygdala reactivity was examined by comparing regional cerebral blood flow, measured with positron emission tomography and [(15)O]water, during exposure to angry and neutral faces, respectively, in a Swedish sample comprising 32 patients with social anxiety disorder and 17 healthy volunteers. In a separate US sample, comprising 85 healthy volunteers studied with blood oxygen level-dependent functional magnetic resonance imaging, amygdala reactivity was assessed by comparing the activity during exposure to threatening faces and neutral geometric shapes, respectively. In both the Swedish and the US sample, 9-repeat carriers displayed higher amygdala reactivity than 10-repeat homozygotes. The results suggest that this polymorphism contributes to individual variability in amygdala reactivity.
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| 2. |
- Tucker, R P, et al.
(författare)
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See-saw rocking: an in vitro model for mechanotransduction research.
- 2014
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Ingår i: Journal of the Royal Society Interface. - : The Royal Society. - 1742-5662 .- 1742-5689. ; 11:97
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Tidskriftsartikel (refereegranskat)abstract
- In vitro mechanotransduction studies, uncovering the basic science of the response of cells to mechanical forces, are essential for progress in tissue engineering and its clinical application. Many varying investigations have described a multitude of cell responses; however, as the precise nature and magnitude of the stresses applied are infrequently reported and rarely validated, the experiments are often not comparable, limiting research progress. This paper provides physical and biological validation of a widely available fluid stimulation device, a see-saw rocker, as an in vitro model for cyclic fluid shear stress mechanotransduction. This allows linkage between precisely characterized stimuli and cell monolayer response in a convenient six-well plate format. Models of one well were discretized and analysed extensively using computational fluid dynamics to generate convergent, stable and consistent predictions of the cyclic fluid velocity vectors at a rocking frequency of 0.5 Hz, accounting for the free surface. Validation was provided by comparison with flow velocities measured experimentally using particle image velocimetry. Qualitative flow behaviour was matched and quantitative analysis showed agreement at representative locations and time points. Maximum shear stress of 0.22 Pa was estimated near the well edge, and time-average shear stress ranged between 0.029 and 0.068 Pa. Human tenocytes stimulated using the system showed significant increases in collagen and GAG secretion at 2 and 7 day time points. This in vitro model for mechanotransduction provides a versatile, flexible and inexpensive method for the fluid shear stress impact on biological cells to be studied.
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| 3. |
- Diehl, Stefan, et al.
(författare)
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A one-dimensional moving-boundary model for tubulin-driven axonal growth.
- 2014
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Ingår i: Journal of Theoretical Biology. - : Elsevier BV. - 1095-8541 .- 0022-5193. ; 358:Online 21 June 2014, s. 194-207
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Tidskriftsartikel (refereegranskat)abstract
- A one-dimensional continuum-mechanical model of axonal elongation due to assembly of tubulin dimers in the growth cone is presented. The conservation of mass leads to a coupled system of three differential equations. A partial differential equation models the dynamic and the spatial behaviour of the concentration of tubulin that is transported along the axon from the soma to the growth cone. Two ordinary differential equations describe the time-variation of the concentration of free tubulin in the growth cone and the speed of elongation. All steady-state solutions of the model are categorized. Given a set of the biological parameter values, it is shown how one easily can infer whether there exist zero, one or two steady-state solutions and directly determine the possible steady-state lengths of the axon. Explicit expressions are given for each stationary concentration distribution. It is thereby easy to examine the influence of each biological parameter on a steady state. Numerical simulations indicate that when there exist two steady states, the one with shorter axon length is unstable and the longer is stable. Another result is that, for nominal parameter values extracted from the literature, in a large portion of a fully grown axon the concentration of free tubulin is lower than both concentrations in the soma and in the growth cone.
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| 4. |
- Henningsson, Anna J., 1972-, et al.
(författare)
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Laboratory diagnosis of Lyme neuroborreliosis: a comparisonof three CSF anti-Borrelia antibody assays
- 2014
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Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer Publishing Company. - 0934-9723 .- 1435-4373. ; 33, s. 797-803
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Tidskriftsartikel (refereegranskat)abstract
- The diagnosis of Lyme neuroborreliosis (LNB) requires the detection of intrathecal synthesis of Borrelia-specific antibodies, but in very early disease, the sensitivity may be low. We compared the performance of the second-generation IDEIA Lyme Neuroborreliosis test (Oxoid), based on purified native flagellum antigen, with two newly developed tests based on several recombinant antigens for the diagnosis of LNB. Patients investigated for LNB during 2003 through 2007 were included (n = 175); 52 with definite LNB, four with possible LNB and 119 non-LNB patients. Serum and cerebrospinal fluid (CSF) were analysed with the IDEIA Lyme Neuroborreliosis (Oxoid), VIDAS Lyme IgG (bioMérieux) and recomBead Borrelia IgM and IgG (Mikrogen) assays. Intrathecal antibody indices (AIs) were calculated according to the manufacturers’ protocols. The IDEIA test performed with an overall sensitivity (IgM and IgG AIs taken together) of 88 % and a specificity of 99 %. The VIDAS test showed a sensitivity of 86 % and a specificity of 97 %. An overall sensitivity of 100 % and a specificity of 97 % were achieved by the recomBead test. We conclude that the three assays performed equally well regarding specificity, but our data suggest an improved diagnostic sensitivity with the recomBead Borrelia test.
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| 5. |
- Henningsson, Frida, et al.
(författare)
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IgE-Mediated Enhancement of CD4(+) T Cell Responses in Mice Requires Antigen Presentation by CD11c(+) Cells and Not by B Cells
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:7, s. e21760-
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Tidskriftsartikel (refereegranskat)abstract
- IgE antibodies, administered to mice together with their specific antigen, enhance antibody and CD4(+) T cell responses to this antigen. The effect is dependent on the low affinity receptor for IgE, CD23, and the receptor must be expressed on B cells. In vitro, IgE-antigen complexes are endocytosed via CD23 on B cells, which subsequently present the antigen to CD4(+) T cells. This mechanism has been suggested to explain also IgE-mediated enhancement of immune responses in vivo. We recently found that CD23(+) B cells capture IgE-antigen complexes in peripheral blood and rapidly transport them to B cell follicles in the spleen. This provides an alternative explanation for the requirement for CD23(+) B cells. The aim of the present study was to determine whether B-cell mediated antigen presentation of IgE-antigen complexes explains the enhancing effect of IgE on immune responses in vivo. The ability of spleen cells, taken from mice 1-4 h after immunization with IgE-antigen, to present antigen to specific CD4(+) T cells was analyzed. Antigen presentation was intact when spleens were depleted of CD19(+) cells (i.e., primarily B cells) but was severely impaired after depletion of CD11c(+) cells (i.e., primarily dendritic cells). In agreement with this, the ability of IgE to enhance proliferation of CD4(+) T cells was abolished in CD11c-DTR mice conditionally depleted of CD11c(+) cells. Finally, the lack of IgE-mediated enhancemen of CD4(+) T cell responses in CD23(-/-) mice could be rescued by transfer of MHC-II-compatible as well as by MHC-II-incompatible CD23(+) B cells. These findings argue against the idea that IgE-mediated enhancement of specific CD4(+) T cell responses in vivo is caused by increased antigen presentation by B cells. A model where CD23(+) B cells act as antigen transporting cells, delivering antigen to CD11c(+) cells for presentation to T cells is consistent with available experimental data.
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| 6. |
- Henningsson, Louise, 1979, et al.
(författare)
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Interleukin 15 Mediates Joint Destruction in Staphylococcus Aureus Arthritis
- 2012
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 206:5, s. 687-696
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Tidskriftsartikel (refereegranskat)abstract
- Background. Staphylococcus aureus arthritis causes severe and rapid joint damage despite antibiotics. Thus, there is a need to identify new treatment targets in addition to antibiotics. Lately, interleukin 15 (IL-15) has been implicated both in osteoclastogenesis and in bacterial clearance-2 important issues in S. aureus-induced joint destruction. This has prompted us to investigate the importance of IL-15 in S. aureus-induced arthritis. Methods.Toxic shock syndrome toxin-1 producing S. aureus was intravenously inoculated in IL-15 knockout and wildtype mice and in wildtype mice treated with anti-IL-15 antibodies (aIL-15ab) or isotype control antibody. Results.Absence of IL-15, either in knockout mice or after treatment with aIL-15ab, significantly reduced weight loss compared with controls during the infection. The severity of synovitis and joint destruction was significantly decreased in IL-15 knockout and aIL-15ab treated mice compared with controls. In IL-15 knockout mice there was a reduced number of osteoclasts in the joints. The host's ability to clear bacteria was not influenced in the IL-15 knockout mice, but significantly increased after treatment with aIL-15ab. Conclusions.IL-15 is a mediator of joint destruction in S. aureus-induced arthritis and contributes to general morbidity, which makes this cytokine an interesting treatment target in addition to conventional antibiotics.
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| 7. |
- Henningsson, S, et al.
(författare)
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Resource dependencies in socio-technical information systems design research
- 2010
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Ingår i: Communications of the Association for Information Systems. - 1529-3181 .- 1529-3181. ; 27:42
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Tidskriftsartikel (refereegranskat)abstract
- An Information Systems (IS) design research project is in many aspects fundamentally different from that of traditional behaviorist research. IS design research projects with the ambition to provide socio-technical solutions to real world problems require the contribution of external stakeholders to the development, testing, and implementation of the design contribution. This article analyzes socio-technical IS design research from a resource dependency perspective. Our objective is to identify and describe critical resources that need to be secured for completion of the research. We investigate three socio-technical IS design research projects. The first project is a small-scale project on design of eLearning courses, the second is a medium-scale industry-driven project on IS integration in corporate mergers and acquisitions, and the third is a large collaborative research project with the ambition to redesign European customs using IT. The most prominent resources are human (knowledge and skills) and organizational (reputation and trust). The main strategy to deal with dependencies is incorporation of resource controllers, which create reciprocal and sequential dependencies internally. Our study shows the importance of extending the existing view of IS design research, when applied to socio-technical research, with an “initiation phase” and an “impact phase,” which are especially important in large-scale design research projects.
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| 8. |
- Holland, John, et al.
(författare)
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Use of IC information in Japanese financial firms
- 2012
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Ingår i: Journal of Intellectual Capital. - : Emerald Group Publishing Limited. - 1469-1930 .- 1758-7468. ; 13:4, s. 562-581
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Tidskriftsartikel (refereegranskat)abstract
- Purpose - The purpose of this paper is to explore how Japanese Financial Institutions (JFI) acquire and use company intellectual capital (IC) information and other associated intangibles information in their common structured and routine equity investment decisions and how this activity contributed to knowledge creation in the JFIs concerning knowledge of companies, markets and emotions.Design/methodogy/approach – The research employed a multi-case design, using four JFI cases. The JFIs and their IC use were discussed in terms of Nonaka and Toyama’s ’theory of the knowledge creating firm’ (2005). The associated concepts of ‘Ba’, ‘SECI’ and ‘Kata’ were conceptually located within the internal and external order emerging in the cases and were used to analyze JFI knowledge creating behavior. Despite the limits to SECI or Kata processes noted in the cases, these concepts were valuable in analyzing the case data.Findings – Company IC information contributed to earnings estimates and company valuation. Impressionistic and emotional information about intangibles contributed to JFI feelings and confidence in their valuation and information use. Both led to investment decisions. JFI knowledge was an important component of the key interacting and informed contexts used by JFIs to make collective sense of these different but complementary types of information in investment decision making. This created opportunities for improved disclosure and accountability between JFIs and their investee companies. Common patterns of behaviour across the JFIs were counterbalanced by variety and differences noted in JFI behaviour. These included differences in JFI investment philosophy and ‘landscape’.Practical implication – The findings provide important insights in how JFI knowledge creating patterns could limit or progress a common language of communication between companies and markets on the subject of intellectual capital. This could impact on the quality of corporate disclosure and accountability processes. The results will be used in the context of a further development of the Disclosure of Intellectual Assets Based Management in Japan.Originality – The paper combines ideas from the ‘knowledge creating firm’ with conventional ideas of finance, and of disclosure and accountability. This combined theoretical analysis demonstrated a novel and robust theoretical context to interpret the unique Japanese case data, and the distinctive empirical patterns emerging from it.
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| 9. |
- Jimenez, Javier, et al.
(författare)
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Abnormally decreased NO and augmented CO production in islets of the leptin-deficient ob/ob mouse might contribute to explain hyperinsulinemia and islet survival in leptin-resistant type 2 obese diabetes.
- 2011
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 170, s. 43-51
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Tidskriftsartikel (refereegranskat)abstract
- The role of the gaseous messengers NO and CO for β-cell function and survival is controversial. We examined this issue in the hyperglycemic-hyperinsulinemic ob/ob mouse, an animal model of type 2 obese diabetes, by studying islets from obese vs lean mice regarding glucose-stimulated insulin release in relation to islet NO and CO production and the influence of modulating peptide hormones. Glucose-stimulated increase in ncNOS-activity in incubated lean islets was converted to a decrease in ob/ob islets associated with markedly increased insulin release. Both types of islet displayed iNOS activity appearing after ~60min in high-glucose. In ob/ob islets the insulinotropic peptides glucagon, GLP-1 and GIP suppressed NOS activities and amplified glucose-stimulated insulin release. The insulinostatic peptide leptin induced the opposite effects. Suppression of islet CO production inhibited, while stimulation amplified glucose-stimulated insulin release. Nonincubated isolated islets from young and adult obese mice displayed very low ncNOS and negligible iNOS activity. In contrast, production of CO, a NOS inhibitor, was impressively raised. Glucose injections induced strong activities of islet NOS isoforms in lean but not in obese mice and confocal microscopy revealed iNOS expression only in lean islets. Islets from ob/ob mice existing in a hyperglycemic in vivo milieu maintain elevated insulin secretion and protection from glucotoxicity through a general suppression of islet NOS activities achieved by leptin deficiency, high CO production and insulinotropic cyclic-AMP-generating hormones. Such a beneficial effect on islet function and survival might have its clinical counterpart in human leptin-resistant type 2 obese diabetes with hyperinsulinemia.
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| 10. |
- Johanson, Ulf, 1944-, et al.
(författare)
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Japanese Financial Institutions and their use of company intangibles informationin company investment decisions – Ba, SECI, Kata and JFIs as knowledge creatingfirms.
- 2010
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Annan publikation (refereegranskat)abstract
- The purpose of this paper is to explore how Japanese Financial Institutions (JFI)acquire and use company intellectual capital (IC) information and other associated intangiblesinformation in their common structured and routine equity investment decisions and how thisactivity contributed to knowledge creation in the JFIs concerning knowledge of companies,markets and emotions. Company IC information contributed to earnings estimates and companyvaluation. Impressionistic and emotional information about intangibles contributed to JFIfeelings and confidence in their valuation and information use. Both led to investmentdecisions. JFI knowledge was an important component of the key interacting and informedcontexts used by JFIs to make collective sense of these different but complementary types ofinformation in investment decision making. This created opportunities for improveddisclosure and accountability between JFIs and their investee companies. Common patterns ofbehaviour across the JFIs were counterbalanced by variety and differences noted in JFIbehaviour. These included differences in JFI investment philosophy and ‘landscape’.
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