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  • 151.
    Peterson, Gunnel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences. Uppsala Univ, Sweden.
    Nilsson, David
    Umea Univ, Sweden.
    Trygg, Johan
    Umea Univ, Sweden.
    Peolsson, Anneli
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Neck-specific exercise improves impaired interactions between ventral neck muscles in chronic whiplash: A randomized controlled ultrasound study2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 9649Article in journal (Refereed)
    Abstract [en]

    Chronic pain and disability is common in whiplash-associated disorders (WAD), leading to personal suffering, sick leave, and social cost. The cervical spine is heavily dependent on muscular support and whiplash injury can cause damage to the neck muscles, but diagnostic tools to measure neck muscle impairment and evaluate exercise interventions are lacking. Therefore, the present study investigated ventral neck muscle interactions in 26 individuals with chronic WAD randomized to neck-specific exercise (NSE) or remaining on a waiting list (WL) in 3 months. We performed real-time, non-invasive ultrasound measurements with speckle tracking analysis and calculated the deformation area and deformation rate in three ventral neck muscles. Multivariate statistics were used to analyse interactions between the muscles. After 3 months of NSE, significant improvements were observed in neck muscle interactions and pain intensity in the NSE group compared to the WL group. Thus, this study demonstrates that non-invasive ultrasound can be a diagnostic tool for muscle impairment and used to evaluate exercise interventions in WAD and stands to make a breakthrough for better management in chronic WAD.

  • 152.
    Peterson, Gunnel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences. Uppsala Univ, Sweden.
    OLeary, Shaun
    Univ Queensland, Australia; Queensland Hlth, Australia.
    Nilsson, David
    Umea Univ, Sweden.
    Moodie, Katherine
    Univ Queensland, Australia.
    Tucker, Kylie
    Univ Queensland, Australia.
    Trygg, Johan
    Umea Univ, Sweden.
    Peolsson, Anneli
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Ultrasound imaging of dorsal neck muscles with speckle tracking analyses - the relationship between muscle deformation and force2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 13688Article in journal (Refereed)
    Abstract [en]

    The development of methods of non-invasive measurement of neck muscle function remains a priority in the clinical sciences. In this study, dorsal neck muscle deformation vs time curves (deformation area) were evaluated against incremental force, recorded from non-invasive real-time ultrasound measurement. The results revealed subject-specific moderate to strong linear or non-linear relationships between deformation and force. Test-retest variability showed strong reliability for all five neck muscles summed together and fair to good reliability for the five muscles evaluated separately. Multivariate statistics were used to analyse the interactions between the dorsal neck muscles during different percentages of maximal voluntary contraction (MVC). Low force (10-20% MVC) was related to muscle shortening; higher force (40-80% MVC) showed combination of shortening and elongation deformation in the muscle interactions. The muscle interactions during isometric MVC test were subject-specific, with different combinations and deformations of the five neck muscles. Force amp;gt;= 40% MVC were associated with a forward movement of the cervical spine that affected the ultrasound measurement of the dorsal neck muscles. Ultrasound with speckle-tracking analyses may be best used to detect low levels (amp;lt;40% MVC) of neck muscle activity.

  • 153.
    Pham, Tuan
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Karlsson, Matilda
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Andersson, Caroline M.
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Mirdell, Robin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Automated VSS-based Burn Scar Assessment using Combined Texture and Color Features of Digital Images in Error-Correcting Output Coding2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 16744Article in journal (Refereed)
    Abstract [en]

    Assessment of burn scars is an important study in both medical research and clinical settings because it can help determine response to burn treatment and plan optimal surgical procedures. Scar rating has been performed using both subjective observations and objective measuring devices. However, there is still a lack of consensus with respect to the accuracy, reproducibility, and feasibility of the current methods. Computerized scar assessment appears to have potential for meeting such requirements but has been rarely found in literature. In this paper an image analysis and pattern classifcation approach for automating burn scar rating based on the Vancouver Scar Scale (VSS) was developed. Using the image data of pediatric patients, a rating accuracy of 85% was obtained, while 92% and 98% were achieved for the tolerances of one VSS score and two VSS scores, respectively. The experimental results suggest that the proposed approach is very promising as a tool for clinical burn scar assessment that is reproducible and cost-efective.

  • 154.
    Pham, Tuan
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Watanabe, Yuzuru
    Fukushima Medical University, Japan.
    Higuchi, Mitsunori
    Fukushima Medical University, Japan.
    Suzuki, Hiroyuki
    Fukushima Medical University, Japan.
    Texture Analysis and Synthesis of Malignant and Benign Mediastinal Lymph Nodes in Patients with Lung Cancer on Computed Tomography2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 43209Article in journal (Refereed)
    Abstract [en]

    Texture analysis of computed tomography (CT) imaging has been found useful to distinguish subtle differences, which are in-visible to human eyes, between malignant and benign tissues in cancer patients. This study implemented two complementary methods of texture analysis, known as the gray-level co-occurrence matrix (GLCM) and the experimental semivariogram (SV) with an aim to improve the predictive value of evaluating mediastinal lymph nodes in lung cancer. The GLCM was explored with the use of a rich set of its derived features, whereas the SV feature was extracted on real and synthesized CT samples of benign and malignant lymph nodes. A distinct advantage of the computer methodology presented herein is the alleviation of the need for an automated precise segmentation of the lymph nodes. Using the logistic regression model, a sensitivity of 75%, specificity of 90%, and area under curve of 0.89 were obtained in the test population. A tenfold cross-validation of 70% accuracy of classifying between benign and malignant lymph nodes was obtained using the support vector machines as a pattern classifier. These results are higher than those recently reported in literature with similar studies.

  • 155.
    Ping Heidi Iu, Yan
    et al.
    Queen Elizabeth Hospital, Peoples R China.
    Helander, Sara
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Zimdahl Kahlin, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Wah Cheng, Chun
    Queen Elizabeth Hospital, Peoples R China.
    Chung Shek, Chi
    Queen Elizabeth Hospital, Peoples R China.
    Ho Leung, Moon
    Queen Elizabeth Hospital, Peoples R China.
    Wallner, Björn
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Mårtensson, Lars-Göran
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Lindqvist Appell, Malin
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    One amino acid makes a difference-Characterization of a new TPMT allele and the influence of SAM on TPMT stability2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 46428Article in journal (Refereed)
    Abstract [en]

    Thiopurine induced toxicity is associated with defects in the thiopurine methyltransferase (TPMT) gene. TPMT is a polymorphic enzyme, with most of the single nucleotide polymorphisms (SNPs) causing an amino acid change, altering the enzymatic activity of the TPMT protein. In this study, we characterize a novel patient allele c.719A amp;gt; C, named TPMT*41, together with the more common variant *3C c.719A amp;gt; G, resulting in an amino acid shift at tyrosine 240 to serine, p.Y240S and cysteine, p.Y240C respectively. We show that the patient heterozygote for c.719A amp;gt; C has intermediate enzymatic activity in red blood cells. Furthermore, in vitro studies, using recombinant protein, show that TPMT p.Y240S is less stable than both TPMTwt and TPMT p.Y240C. The addition of SAM increases the stability and, in agreement with Isothermal Titration Calorimetry (ITC) data, higher molar excess of SAM is needed in order to stabilize TPMT p.Y240C and TPMT p.Y240S compared to TPMTwt. Molecular dynamics simulations show that the loss of interactions is most severe for Y240S, which agrees with the thermal stability of the mutations. In conclusion, our study shows that SAM increases the stability of TPMT and that changing only one amino acid can have a dramatic effect on TPMT stability and activity.

  • 156.
    Pozina, Galia
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Forsberg, Mathias
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Kaliteevski, M. A.
    St Petersburg Academic University, Russia; ITMO University, Russia.
    Hemmingsson, Carl
    Linköping University, Department of Physics, Chemistry and Biology, Semiconductor Materials. Linköping University, Faculty of Science & Engineering.
    Emission properties of Ga2O3 nano-flakes: effect of excitation density2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 42132Article in journal (Refereed)
    Abstract [en]

    In the quest of developing high performance electronic and optical devices and more cost effective fabrication processes of monoclinic beta-Ga2O3, new growth techniques and fundamental electronic and optical properties of defects have to be explored. By heating of dissolved metallic Ga in HCl in a NH3 and N-2 atmosphere, nano-flake films of monoclinic beta-phase Ga2O3 were grown as confirmed by XRD. From optical measurements, we observe two strong emissions. A red band peaking at similar to 2.0 eV and a UV band at similar to 3.8 eV. The band at similar to 2.0 eV is attributed to donor-acceptor pair recombination where the donor and acceptor level is suggested to be related to VO and nitrogen, respectively. By studying the dependence of the intensity of the UV band at 3.8 eV versus excitation density, a model is suggested. In the model, it is assumed that local potential fluctuations forming minima (maxima), where the carriers would be localized with a summarized band offset for conduction and valence band of 1 eV. The origin of the fluctuations is tentatively suggested to be related to micro-inclusions of different phases in the film.

  • 157.
    Pozina, Galia
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Gubaydullin, Azat R.
    St Petersburg Acad Univ, Russia; ITMO Univ, Russia.
    Mitrofanov, Maxim I.
    Ioffe Inst, Russia; SHM RandE Ctr RAS, Russia.
    Kaliteevski, Mikhail A.
    St Petersburg Acad Univ, Russia; ITMO Univ, Russia; Ioffe Inst, Russia.
    Levitskii, Iaroslav V.
    Ioffe Inst, Russia; SHM RandE Ctr RAS, Russia.
    Voznyuk, Gleb V.
    ITMO Univ, Russia.
    Tatarinov, Evgeniy E.
    ITMO Univ, Russia.
    Evtikhiev, Vadim P.
    Ioffe Inst, Russia.
    Rodin, Sergey N.
    Ioffe Inst, Russia; SHM RandE Ctr RAS, Russia.
    Kaliteevskiy, Vasily N.
    Lappeenranta Univ Technol, Finland.
    Chechurin, Leonid S.
    Lappeenranta Univ Technol, Finland.
    Approach to high quality GaN lateral nanowires and planar cavities fabricated by focused ion beam and metal-organic vapor phase epitaxy2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 7218Article in journal (Refereed)
    Abstract [en]

    We have developed a method to fabricate GaN planar nanowires and cavities by combination of Focused Ion Beam (FIB) patterning of the substrate followed by Metal Organic Vapor Phase Epitaxy (MOVPE). The method includes depositing a silicon nitride mask on a sapphire substrate, etching of the trenches in the mask by FIB with a diameter of 40 nm with subsequent MOVPE growth of GaN within trenches. It was observed that the growth rate of GaN is substantially increased due to enhanced bulk diffusion of the growth precursor therefore the model for analysis of the growth rate was developed. The GaN strips fabricated by this method demonstrate effective luminescence properties. The structures demonstrate enhancement of spontaneous emission via formation of Fabry-Perot modes.

  • 158.
    Pozina, Galia
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Ivanov, Konstantin A.
    ITMO Univ, Russia.
    Morozov, Konstantin M.
    St Petersburg Acad Univ, Russia.
    Girshova, Elizaveta I.
    St Petersburg Acad Univ, Russia.
    Egorov, Anton Yu.
    ITMO Univ, Russia; Ioffe Inst, Russia.
    Clark, Stewart J.
    Univ Durham, England.
    Kaliteevski, Mikhail A.
    ITMO Univ, Russia; St Petersburg Acad Univ, Russia; Ioffe Inst, Russia.
    Enhancement of light emission in Bragg monolayer-thick quantum well structures2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 10162Article in journal (Refereed)
    Abstract [en]

    Control over spontaneous emission rate is important for improving efficiency in different semiconductor applications including lasers, LEDs and photovoltaics. Usually, an emitter should be placed inside the cavity to increase the spontaneous emission rate, although it is technologically challenging. Here we experimentally demonstrate a phenomenon of super-radiance observed in a cavity-less periodic Bragg structure based on InAs monolayer-thick multiple quantum wells (MQW). The collective super-radiant mode shows enhanced emission rate for specific angles and frequencies. This behaviour correlates with the calculations demonstrating individual spots of the enhanced Purcell coefficient near the Bragg condition curve. This study provides a perspective for realization of surface emitting cavity-less lasers with distributed feedback.

  • 159.
    Pozina, Galia
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Kaliteevski, M. A.
    St Petersburg Academic University, Russia; Russian Academic Science, Russia; ITMO University, Russia.
    Nikitina, E. V.
    St Petersburg Academic University, Russia; Russian Academic Science, Russia.
    Denisov, D. V.
    St Petersburg Academic University, Russia; Russian Academic Science, Russia.
    Polyakov, N. K.
    St Petersburg Academic University, Russia.
    Pirogov, E. V.
    St Petersburg Academic University, Russia.
    Goray, L. I.
    St Petersburg Academic University, Russia.
    Gubaydullin, A. R.
    St Petersburg Academic University, Russia; ITMO University, Russia.
    Ivanov, K. A.
    ITMO University, Russia.
    Kaliteevskaya, N. A.
    St Petersburg Academic University, Russia; ITMO University, Russia; University of Durham, England.
    Egorov, A. Yu.
    Russian Academic Science, Russia; ITMO University, Russia.
    Clark, S. J.
    University of Durham, England.
    Super-radiant mode in InAs-monolayer-based Bragg structures2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, no 14911Article in journal (Refereed)
    Abstract [en]

    We report direct experimental evidence of the collective super-radiant mode in Bragg structure containing 60 InAs monolayer-based quantum wells (QWs) periodically arranged in GaAs matrix. Time-resolved photoluminescence measurements reveal an appearance of the additional super-radiant mode, originated from coherent collective interaction of QWs. This mode demonstrates a super-linear dependence of the intensity and radiative decay rate on the excitation power. The superradiant mode is not manifested in the case if only a small number of QWs is excited.

  • 160.
    Pértille, Fábio
    et al.
    1Animal Biotechnology Laboratory, Animal Science and Pastures Department, University of São Paulo (USP)/Luiz de Queiroz College of Agriculture (ESALQ), Piracicaba, São Paulo, Brazil.
    Guerrero-Bosagna, Carlos
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    da Silva, Vinicius Henrique
    1Animal Biotechnology Laboratory, Animal Science and Pastures Department, University of São Paulo (USP)/Luiz de Queiroz College of Agriculture (ESALQ), Piracicaba, São Paulo, Brazil.
    Boschiero, Clarissa
    1Animal Biotechnology Laboratory, Animal Science and Pastures Department, University of São Paulo (USP)/Luiz de Queiroz College of Agriculture (ESALQ), Piracicaba, São Paulo, Brazil..
    da Silva Nunes, José de Ribamar
    1Animal Biotechnology Laboratory, Animal Science and Pastures Department, University of São Paulo (USP)/Luiz de Queiroz College of Agriculture (ESALQ), Piracicaba, São Paulo, Brazil..
    Corrêa Ledur, Mônica
    Brazilian Agricultural Research Corporation (EMBRAPA) Swine & Poultry, Concórdia, Santa Catarina, Brazil.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Lehmann Coutinho, Luiz
    1Animal Biotechnology Laboratory, Animal Science and Pastures Department, University of São Paulo (USP)/Luiz de Queiroz College of Agriculture (ESALQ), Piracicaba, São Paulo, Brazil.
    High-throughput and Cost-effective Chicken Genotyping Using Next-Generation Sequencing2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 26929Article in journal (Refereed)
    Abstract [en]

    Chicken genotyping is becoming common practice in conventional animal breeding improvement.Despite the power of high-throughput methods for genotyping, their high cost limits large scale use inanimal breeding and selection. In the present paper we optimized the CornellGBS, an efficient and costeffectivegenotyping by sequence approach developed in plants, for its application in chickens. Herewe describe the successful genotyping of a large number of chickens (462) using CornellGBS approach.Genomic DNA was cleaved with the PstI enzyme, ligated to adapters with barcodes identifyingindividual animals, and then sequenced on Illumina platform. After filtering parameters were applied,134,528 SNPs were identified in our experimental population of chickens. Of these SNPs, 67,096 hada minimum taxon call rate of 90% and were considered ‘unique tags’. Interestingly, 20.7% of theseunique tags have not been previously reported in the dbSNP. Moreover, 92.6% of these SNPs wereconcordant with a previous Whole Chicken-genome re-sequencing dataset used for validation purposes.The application of CornellGBS in chickens showed high performance to infer SNPs, particularly inexonic regions and microchromosomes. This approach represents a cost-effective (~US$50/sample)and powerful alternative to current genotyping methods, which has the potential to improve wholegenomeselection (WGS), and genome-wide association studies (GWAS) in chicken production.

  • 161.
    Rajan, Meenu Rohini
    et al.
    Univ Gothenburg, Sweden.
    Sotak, Matus
    Univ Gothenburg, Sweden.
    Barrenas, Fredrik
    Univ Gothenburg, Sweden; Uppsala Univ, Sweden.
    Shen, Tong
    Univ Calif Davis, CA 95616 USA.
    Borkowski, Kamil
    Univ Calif Davis, CA 95616 USA.
    Ashton, Nicholas J.
    Univ Gothenburg, Sweden; Kings Coll London, England; NIHR Biomed Res Ctr Mental Hlth, England; Biomed Res Unit Dementia South London, England; Maudsley NHS Fdn, England.
    Biorserud, Christina
    Univ Gothenburg, Sweden.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Ramström, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Orebro Univ, Sweden.
    Scholl, Michael
    Univ Gothenburg, Sweden; UCL, England.
    Lindahl, Per
    Univ Gothenburg, Sweden.
    Fiehn, Oliver
    Univ Calif Davis, CA 95616 USA.
    Newman, John W.
    Univ Calif Davis, CA 95616 USA; ARS, CA USA.
    Perkins, Rosie
    Univ Gothenburg, Sweden.
    Wallenius, Ville
    Univ Gothenburg, Sweden.
    Lange, Stephan
    Univ Gothenburg, Sweden; Univ Calif San Diego, CA 92103 USA.
    Borgeson, Emma
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Comparative analysis of obesity-related cardiometabolic and renal biomarkers in human plasma and serum2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 15385Article in journal (Refereed)
    Abstract [en]

    The search for biomarkers associated with obesity-related diseases is ongoing, but it is not clear whether plasma and serum can be used interchangeably in this process. Here we used high-throughput screening to analyze 358 proteins and 76 lipids, selected because of their relevance to obesity-associated diseases, in plasma and serum from age- and sex-matched lean and obese humans. Most of the proteins/lipids had similar concentrations in plasma and serum, but a subset showed significant differences. Notably, a key marker of cardiovascular disease PAI-1 showed a difference in concentration between the obese and lean groups only in plasma. Furthermore, some biomarkers showed poor correlations between plasma and serum, including PCSK9, an important regulator of cholesterol homeostasis. Collectively, our results show that the choice of biofluid may impact study outcome when screening for obesity-related biomarkers and we identify several markers where this will be the case.

  • 162.
    Religa, Piotr
    et al.
    Karolinska Institute, Sweden .
    Cao, Renhai
    Karolinska Institute, Sweden .
    Religa, Dorota
    Karolinska Institute, Sweden .
    Xue, Yuan
    Karolinska Institute, Sweden .
    Bogdanovic, Nenad
    Karolinska Institute, Sweden .
    Westaway, David
    University of Toronto, Canada .
    Marti, Hugo H.
    Heidelberg University, Germany .
    Winblad, Bengt
    Karolinska Institute, Sweden .
    Cao, Yihai
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    VEGF significantly restores impaired memory behavior in Alzheimers mice by improvement of vascular survival2013In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 3Article in journal (Refereed)
    Abstract [en]

    The functional impact of amyloid peptides (Abs) on the vascular system is less understood despite these pathologic peptides are substantially deposited in the brain vasculature of Alzheimers patients. Here we show substantial accumulation of Abs 40 and 42 in the brain arterioles of Alzheimers patients and of transgenic Alzheimers mice. PurifiedAbs 1-40 and 1-42 exhibited vascular regression activity in the in vivo animal models and vessel density was reversely correlated with numbers and sizes of amyloid plaques in human patients. A significant high number of vascular cells underwent cellular apoptosis in the brain vasculature of Alzheimers patients. VEGF significantly prevented Ab-induced endothelial apoptosis in vitro. Neuronal expression of VEGF in transgenic mice restored memory behavior of Alzheimers. These findings provide conceptual implication of improvement of vascular functions as a novel therapeutic approach for the treatment of Alzheimers disease.

  • 163.
    Ren, Tianying
    et al.
    Oregon Health and Science University, OR 97239 USA .
    He, Wenxuan
    Oregon Health and Science University, OR 97239 USA .
    Li, Yizeng
    University of Michigan, MI 48109 USA .
    Grosh, Karl
    University of Michigan, MI 48109 USA.
    Fridberger, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Light-induced vibration in the hearing organ2014In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 4, p. 5941-Article in journal (Refereed)
    Abstract [en]

    The exceptional sensitivity of mammalian hearing organs is attributed to an active process, where force produced by sensory cells boost sound-induced vibrations, making soft sounds audible. This process is thought to be local, with each section of the hearing organ capable of amplifying sound-evoked movement, and nearly instantaneous, since amplification can work for sounds at frequencies up to 100 kHz in some species. To test these fundamental precepts, we developed a method for focally stimulating the living hearing organ with light. Light pulses caused intense and highly damped mechanical responses followed by traveling waves that developed with considerable delay. The delayed response was identical to movements evoked by click-like sounds. This shows that the active process is neither local nor instantaneous, but requires mechanical waves traveling from the cochlear base toward its apex. A physiologically-based mathematical model shows that such waves engage the active process, enhancing hearing sensitivity.

  • 164.
    Ribeiro Jr, Luiz Antonio
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Physics. Linköping University, Faculty of Science & Engineering. Institute of Physics, University of Brasίlia, Brasίlia, Brazil.
    da Silva, Gesiel Gomes
    Institute of Physics, University of Brasίlia, Brasίlia, Brazil; Goias Federal Institute of Science and Technology, IFG, Luziânia, Brazil.
    de Sousa Jr, Rafael Timoteo
    Department of Electrical Engineering, University of Brasίlia, Brasίlia, Brazil.
    de Almeida Fonseca, Antonio Luciano
    Institute of Physics, University of Brasίlia, Brasίlia, Brazil.
    da Cunha, Wiliam Ferreira
    Institute of Physics, University of Brasίlia, Brasίlia, Brazil.
    Magela e Silva, Geraldo
    Institute of Physics, University of Brasίlia, Brasίlia, Brazil.
    Spin-Orbit Effects on the Dynamical Properties of Polarons in Graphene Nanoribbons2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 1914Article in journal (Refereed)
    Abstract [en]

    The dynamical properties of polarons in armchair graphene nanoribbons (GNR) is numerically investigated in the framework of a two-dimensional tight-binding model that considers spin-orbit (SO) coupling and electron-lattice (e-l) interactions. Within this physical picture, novel polaron properties with no counterparts to results obtained from conventional tight-binding models are obtained. Our findings show that, depending on the systems width, the presence of SO coupling changes the polarons charge localization giving rise to different degrees of stability for the charge carrier. For instance, the joint action of SO coupling and e-l interactions could promote a slight increase on the charge concentration in the center of the lattice deformation associated to the polaron. As a straightforward consequence, this process of increasing stability would lead to a depreciation in the polarons motion by decreasing its saturation velocity. Our finds are in good agreement with recent experimental investigations for the charge localization in GNR, mostly when it comes to the influence of SO coupling. Moreover, the contributions reported here provide a reliable method for future works to evaluate spin-orbit influence on the performance of graphene nanoribbons.

  • 165.
    Ribeiro, Luiz Antonio
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Physics. Linköping University, Faculty of Science & Engineering.
    Monteiro, Fabio Ferreira
    Univ Brasilia, Brazil.
    da Cunha, Wiliam Ferreira
    Univ Florida, FL 32611 USA.
    Magela e Silva, Geraldo
    Univ Brasilia, Brazil.
    Charge Carrier Scattering in Polymers: A New Neutral Coupled Soliton Channel2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 6595Article in journal (Refereed)
    Abstract [en]

    The dynamical scattering of two oppositely charged bipolarons in non-degenerate organic semiconducting lattices is numerically investigated in the framework of a one-dimensional tight-biding-Hubbard model that includes lattice relaxation. Our findings show that it is possible for the bipolaron pair to merge into a state composed of a confined soliton-antisoliton pair, which is characterized by the appearance of states within less than 0.1 eV from the Fermi level. This compound is in a narrow analogy to a meson confining a quark-antiquark pair. Interestingly, solitons are quasi-particles theoretically predicted to arise only in polymer lattices with degenerate ground state: in the general case of nondegenerate ground state polymers, isolated solitons are not allowed.

  • 166.
    Rivera Vila, Henrique Vieira
    et al.
    Univ Brasilia, Brazil.
    Ribeiro, Luiz Antonio
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Physics. Linköping University, Faculty of Science & Engineering. Univ Brasilia, Brazil.
    Machado de Macedo, Luiz Guilherme
    Fed Univ Para, Brazil.
    Gargano, Ricardo
    Univ Brasilia, Brazil.
    On the Angular Distribution of the H+Li-2 Cross Sections: a Converged Time-Independent Quantum Scattering Study2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 1044Article in journal (Refereed)
    Abstract [en]

    A thorough time-independent quantum scattering study is performed on a benchmark potential energy surface for the H+Li-2 reaction at the fundamental electronic state. Integral and differential cross sections are calculated along with thermal rate coefficients until convergence is reached. Our findings show that vibrational and rotational excitations of the reactant hinder reactivity, though for the latter a considerable reaction promotion was spotted as we increase the reactant rotational quantum number until the critical value of j = 4. Such a promotion then begins to retract, eventually becoming an actual inhibition for larger j. In a straightforward manner, the concept of time-independent methods implemented in this study allowed this accurate state-to-state analysis. Furthermore, a nearly isotropic behaviour of the scattering is noted to take place from the angular point of view. Remarkably, our computational protocol is ideally suited to yield converged thermal rate coefficients, revealing a non-Arrhenius pattern and showing that J-shifting approach fails to describe this particular reaction. Our results, when compared to previous and independent ones, reinforce the latest theoretical reference for future validation in the experimental field.

  • 167.
    Roepke, E. Rasmark
    et al.
    Malmo and Lund Univ, Sweden.
    Bruno, Valentina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Tor Vergata Univ Hosp, Italy; Tor Vergata Univ Hosp, Italy.
    Nedstrand, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Boij, Roland
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Strid, C. Petersson
    Kalmar Hosp, Sweden.
    Piccione, E.
    Tor Vergata Univ Hosp, Italy.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Svensson Arvelund, Judit
    Linköping University, Department of Clinical and Experimental Medicine, Division of Hematopoiesis and Developmental Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Rubér, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Low-molecular-weight-heparin increases Th1-and Th17-associated chemokine levels during pregnancy in women with unexplained recurrent pregnancy loss: a randomised controlled trial2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 12314Article in journal (Refereed)
    Abstract [en]

    Low-molecular-weight heparin (LMWH) is widely used to treat recurrent pregnancy loss (RPL) because of its anti-coagulant effects. Although in vitro studies have suggested additional immunological effects, these are debated. We therefore investigated whether LMWH could modulate immune responses in vivo during pregnancy of women with unexplained RPL. A Swedish open multi-centre randomised controlled trial included 45 women treated with tinzaparin and 42 untreated women. Longitudinally collected plasma samples were obtained at gestational weeks (gw) 6, 18, 28 and 34 and analysed by multiplex bead technology for levels of 11 cytokines and chemokines, chosen to represent inflammation and T-helper subset-associated immunity. Mixed linear models test on LMWH-treated and untreated women showed differences during pregnancy of the Th1-associated chemokines CXCL10 (p = 0.01), CXCL11 (p amp;lt; 0.001) and the Th17-associated chemokine CCL20 (p = 0.04), while CCL2, CCL17, CCL22, CXCL1, CXCL8, CXCL12, CXCL13 and IL-6 did not differ. Subsequent Students t-test showed significantly higher plasma levels of CXCL10 and CXCL11 in treated than untreated women at gw 28 and 34. The consistent increase in the two Th1-associated chemokines suggests a potential proinflammatory and unfavourable effect of LMWH treatment during later stages of pregnancy, when Th1 immunity is known to disrupt immunological tolerance.

  • 168.
    Roth, Lina
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Olsen Faresjö, Åshild
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Hair cortisol varies with season and lifestyle and relates to human interactions in German shepherd dogs2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 19631Article in journal (Refereed)
    Abstract [en]

    It is challenging to measure long-term endocrine stress responses in animals. We investigated whether cortisol extracted from dog hair reflected the levels of activity and stress long-term, during weeks and months. Hair samples from in total 59 German shepherds were analysed. Samples for measuring cortisol concentrations were collected at three occasions and we complemented the data with individual scores from the Canine Behavioural Assessment and Research Questionnaire (C-BARQ). Generalised linear mixed model (GLMM) results showed that hair cortisol varied with season and lifestyle: competition dogs had higher levels than companion, and professional working dogs, and levels were higher in January than in May and September. In addition, a positive correlation was found between the cortisol levels and the C-BARQ score for stranger-directed aggression (r = 0.31, P = 0.036). Interestingly, the factor "playing often with the dog" (r = -0.34, P = 0.019) and "reward with a treat/toy when the dog behaves correctly" (r = -0.37, P = 0.010) correlated negatively with cortisol levels, suggesting that positive human interactions reduce stress. In conclusion, hair cortisol is a promising method for revealing the activity of the HPA-axis over a longer period of time, and human interactions influence the cortisol level in dogs.

  • 169.
    Rörby, Emma
    et al.
    Lund University Hospital, Sweden.
    Billing, Matilda
    Lund University Hospital, Sweden.
    Dahl, Maria
    Lund University Hospital, Sweden.
    Warsi, Sarah
    Lund University Hospital, Sweden.
    Andradottir, Silja
    Lund University Hospital, Sweden.
    Miharada, Kenichi
    Lund University Hospital, Sweden.
    Siva, Kavitha
    Lund University Hospital, Sweden.
    Jönsson, Jan-Ingvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Blank, Ulrika
    Lund University Hospital, Sweden.
    Karlsson, Goran
    Lund University, Sweden.
    Karlsson, Stefan
    Lund University Hospital, Sweden.
    The stem cell regulator PEDF is dispensable for maintenance and function of hematopoietic stem cells2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 10134Article in journal (Refereed)
    Abstract [en]

    Pigment epithelium derived factor (PEDF), a ubiquitously expressed 50 kDa secreted glycoprotein, was recently discovered to regulate self-renewal of neural stem cells and have a supportive effect on human embryonic stem cell growth. Here, we analyzed expression of PEDF in the murine hematopoietic stem cell (HSC) compartments and found that PEDF is highly expressed in primary long-term HSCs. Therefore, we characterized the hematopoietic system in a knockout mouse model for PEDF and using this model we surprisingly found that PEDF is dispensable for HSC regulation. PEDF knockout mice exhibit normal hematopoiesis in steady state conditions and the absence of PEDF lead to normal regeneration capacity in a serial competitive transplantation setting. Additionally, PEDF-deficient cells exhibit unaltered lineage distribution upon serial transplantations. When human cord blood stem and progenitor cells were cultured in media supplemented with recombinant PEDF they did not show changes in growth potential. Taken together, we report that PEDF is not a critical regulatory factor for HSC function during regeneration in vivo or growth of human stem/progenitor cells in vitro.

  • 170.
    Savio, Monica
    et al.
    University of Pavia, Italy.
    Ferraro, Daniela
    University of Pavia, Italy.
    Maccario, Cristina
    University of Pavia, Italy.
    Vaccarone, Rita
    University of Pavia, Italy.
    Jensen, Lasse
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Karolinska Institute, Sweden.
    Corana, Federica
    University of Pavia, Italy.
    Mannucci, Barbara
    University of Pavia, Italy.
    Bianchi, Livia
    University of Pavia, Italy.
    Cao, Yihai
    Karolinska Institute, Sweden.
    Anna Stivala, Lucia
    University of Pavia, Italy.
    Resveratrol analogue 4,4 -dihydroxy-trans-stilbene potently inhibits cancer invasion and metastasis2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 19973Article in journal (Refereed)
    Abstract [en]

    We investigated the preventive effects of resveratrol analogue 4,4-dihydroxy-trans-stilbene (DHS) on cancer invasion and metastasis. Two different in vivo approaches of mouse and zebrafish lung cancer invasion models were employed in our study. The in vitro results showed that DHS displays potent inhibition on anchorage-dependent or -independent cell growth of LLC cells, leading to impairment of the cell cycle progression with reduction of cell numbers arresting at the G1 phase, an evident accumulation of pre-G1 events correlated with apoptotic behaviour. In addition, DHS induces a marked inhibition of LLC cell migration and matrigel invasion. In a murine lung cancer model, tumour volume, cell proliferation, and tumour angiogenesis were significantly inhibited by DHS. Importantly, liver metastatic lesions were significantly reduced in DHS-treated mice. Similarly, DHS significantly inhibits lung cancer cell dissemination, invasion and metastasis in a zebrafish tumour model. These findings demonstrate that DHS could potentially be developed as a novel therapeutic agent for treatment of cancer and metastasis.

  • 171.
    Selegård, Robert
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Aronsson, Christopher
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Brommesson, Caroline
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Dånmark, Staffan
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Folding driven self-assembly of a stimuli-responsive peptide-hyaluronan hybrid hydrogel2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 7013Article in journal (Refereed)
    Abstract [en]

    Protein-metal ion interactions are ubiquitous in nature and can be utilized for controlling the self-assembly of complex supramolecular architectures and materials. Here, a tunable supramolecular hydrogel is described, obtained by self-assembly of a Zn2+-responsive peptide-hyaluronic acid hybrid synthesized using strain promoted click chemistry. Addition of Zn2+ triggers folding of the peptides into a helix-loop-helix motif and dimerization into four-helix bundles, resulting in hydrogelation. Removal of the Zn2+ by chelators results in rapid hydrogel disassembly. Degradation of the hydrogels can also be time-programed by encapsulation of a hydrolyzing enzyme within the gel, offering multiple possibilities for modulating materials properties and release of encapsulated species. The hydrogel further shows potential antioxidant properties when evaluated using an in vitro model for reactive oxygen species.

  • 172.
    Selvaraj, Karthik
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Mofers, Arjan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Pellegrini, Paola
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Salomonsson, Johannes
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Ahlner, Alexandra
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Morad, Vivian
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Hillert, Ellin-Kristina
    Karolinska Inst, Sweden.
    Espinosa, Belen
    Karolinska Inst, Sweden.
    Arner, Elias S. J.
    Karolinska Inst, Sweden.
    Jensen, Lasse
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Malmstrom, Jonas
    Recipharm AB, Sweden.
    Turkina, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    D´arcy, Padraig
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Walters, Michael A.
    Univ Minnesota, MN 55455 USA.
    Sunnerhagen, Maria
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Linder, Stig
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Cytotoxic unsaturated electrophilic compounds commonly target the ubiquitin proteasome system2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 9841Article in journal (Refereed)
    Abstract [en]

    A large number of natural products have been advocated as anticancer agents. Many of these compounds contain functional groups characterized by chemical reactivity. It is not clear whether distinct mechanisms of action can be attributed to such compounds. We used a chemical library screening approach to demonstrate that a substantial fraction (similar to 20%) of cytotoxic synthetic compounds containing Michael acceptor groups inhibit proteasome substrate processing and induce a cellular response characteristic of proteasome inhibition. Biochemical and structural analyses showed binding to and inhibition of proteasome-associated cysteine deubiquitinases, in particular ubiquitin specific peptidase 14 (USP14). The results suggested that compounds bind to a crevice close to the USP14 active site with modest affinity, followed by covalent binding. A subset of compounds was identified where cell death induction was closely associated with proteasome inhibition and that showed significant antineoplastic activity in a zebrafish embryo model. These findings suggest that proteasome inhibition is a relatively common mode of action by cytotoxic compounds containing Michael acceptor groups and help to explain previous reports on the antineoplastic effects of natural products containing such functional groups.

  • 173.
    Serban, Alexandra
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Palisaitis, Justinas
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Yeh, Chia-Cheng
    National Cheng Kung University, Taiwan.
    Hsu, Hsu-Cheng
    National Cheng Kung University, Taiwan.
    Tsai, Yu-Lin
    National Chiao Tung University, Taiwan.
    Kuo, Hao-Chung
    National Chiao Tung University, Taiwan.
    Junaid, Muhammad
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Hultman, Lars
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Persson, Per O A
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Birch, Jens
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Hsiao, Ching-Lien
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Selective-area growth of single-crystal wurtzite GaN nanorods on SiOx/Si(001) substrates by reactive magnetron sputter epitaxy exhibiting single-mode lasing2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 12701Article in journal (Refereed)
    Abstract [en]

    Selective-area growth (SAG) of single-crystal wurtzite GaN nanorods (NRs) directly onto Si(001) substrates with un-etched native SiOx amorphous layer, assisted by a patterning TiNx mask fabricated by nanosphere lithography (NSL), has been realized by reactive magnetron sputter epitaxy (MSE). The GaN NRs were grown vertically to the substrate surface with the growth direction along c-axis in the well-defined nano-opening areas. A 5-step structural and morphological evolution of the SAG NRs observed at different sputtering times depicts a comprehensive growth model, listed in sequence as: formation of a polycrystalline wetting layer, predominating c-axis oriented nucleation, coarsening and coalescence of multi-islands, single NR evolution, and finally quasi-equilibrium crystal shape formation. Room-temperature cathodoluminescence spectroscopy shows a strong GaN bandedge emission with a uniform luminescence across the NRs, indicating that the SAG NRs are grown with high quality and purity. In addition, single-longitudinal-mode lasing, attributed to well-faceted NR geometry forming a Fabry-Perot cavity, was achieved by optical pumping, paving a way for fabricating high-performance laser optoelectronics using MSE.

  • 174.
    Shtepliuk, Ivan
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Semiconductor Materials. Linköping University, Faculty of Science & Engineering. NASU, Ukraine.
    Caffrey, Nuala M.
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering. Trinity Coll Dublin, Ireland; Trinity Coll Dublin, Ireland.
    Iakimov, Tihomir
    Linköping University, Department of Physics, Chemistry and Biology, Semiconductor Materials. Linköping University, Faculty of Science & Engineering.
    Khranovskyy, Volodymyr
    Linköping University, Department of Physics, Chemistry and Biology, Semiconductor Materials. Linköping University, Faculty of Science & Engineering.
    Abrikosov, Igor
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Physics. Linköping University, Faculty of Science & Engineering. National University of Science and Technology MISIS, Russia.
    Yakimova, Rositsa
    Linköping University, Department of Physics, Chemistry and Biology, Semiconductor Materials. Linköping University, Faculty of Science & Engineering.
    On the interaction of toxic Heavy Metals (Cd, Hg, Pb) with graphene quantum dots and infinite graphene2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 3934Article in journal (Refereed)
    Abstract [en]

    The promise of graphene and its derivatives as next generation sensors for real-time detection of toxic heavy metals (HM) requires a clear understanding of behavior of these metals on the graphene surface and response of the graphene to adsorption events. Our calculations herein were focused on the investigation of the interaction between three HMs, namely Cd, Hg and Pb, with graphene quantum dots (GQDs). We determine binding energies and heights of both neutral and charged HM ions on these GQDs. The results show that the adsorption energy of donor-like physisorbed neutral Pb atoms is larger than that of either Cd or Hg. In contrast to the donor-like behavior of elemental HMs, the chemisorbed charged HM species act as typical acceptors. The energy barriers to migration of the neutral adatoms on GQDs are also estimated. In addition, we show how the substitution of a carbon atom by a HM adatom changes the geometric structure of GQDs and hence their electronic and vibrational properties. UV-visible absorption spectra of HM-adsorbed GQDs vary with the size and shape of the GQD. Based on our results, we suggest a route towards the development of a graphene-based sensing platform for the optical detection of toxic HMs.

  • 175.
    Shubina, T. V.
    et al.
    AF Ioffe Phys Technical Institute, Russia.
    Pozina, Galia
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Jmerik, V. N.
    AF Ioffe Phys Technical Institute, Russia.
    Davydov, V. Yu.
    AF Ioffe Phys Technical Institute, Russia.
    Hemmingsson, Carl
    Linköping University, Department of Physics, Chemistry and Biology, Semiconductor Materials. Linköping University, Faculty of Science & Engineering.
    Andrianov, A. V.
    AF Ioffe Phys Technical Institute, Russia.
    Kazanov, D. R.
    AF Ioffe Phys Technical Institute, Russia.
    Ivanov, S. V.
    AF Ioffe Phys Technical Institute, Russia.
    III-nitride tunable cup-cavities supporting quasi whispering gallery modes from ultraviolet to infrared2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, no 17970Article in journal (Refereed)
    Abstract [en]

    Rapidly developing nanophotonics needs microresonators for different spectral ranges, formed by chip-compatible technologies. In addition, the tunable ones are much in demand. Here, we present site-controlled III-nitride monocrystal cup-cavities grown by molecular beam epitaxy. The cup-cavities can operate from ultraviolet to near-infrared, supporting quasi whispering gallery modes up to room temperature. Besides, their energies are identical in large ripened crystals. In these cavities, the refractive index variation near an absorption edge causes the remarkable effect of mode switching, which is accompanied by the spatial redistribution of electric field intensity with concentration of light into a subwavelength volume. Our results shed light on the mode behavior in semiconductor cavities and open the way for single-growth-run manufacturing the devices comprising an active region and a cavity with tunable mode frequencies.

  • 176.
    Silva, Gesiel Gomes
    et al.
    Goias Fed Inst Educ Sci and Technol, Brazil.
    Ribeiro, Luiz Antonio
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Physics. Linköping University, Faculty of Science & Engineering. Univ Brasilia, Brazil; Univ Brasilia, Brazil.
    Pereira Junior, Marcelo Lopes
    Univ Brasilia, Brazil.
    de Almeida Fonseca, Antonio Luciano
    Univ Brasilia, Brazil; Univ Brasilia, Brazil.
    de Sousa Junior, Rafael Timoteo
    Univ Brasilia, Brazil.
    Magela e Silva, Geraldo
    Univ Brasilia, Brazil.
    Bipolaron Dynamics in Graphene Nanoribbons2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 2909Article in journal (Refereed)
    Abstract [en]

    Graphene nanoribbons (GNRs) are two-dimensional structures with a rich variety of electronic properties that derive from their semiconducting band gaps. In these materials, charge transport can occur via a hopping process mediated by carriers formed by self-interacting states between the excess charge and local lattice deformations. Here, we use a two-dimensional tight-binding approach to reveal the formation of bipolarons in GNRs. Our results show that the formed bipolarons are dynamically stable even for high electric field strengths when it comes to GNRs. Remarkably, the bipolaron dynamics can occur in acoustic and optical regimes concerning its saturation velocity. The phase transition between these two regimes takes place for a critical field strength in which the bipolaron moves roughly with the speed of sound in the material.

  • 177.
    Slezak, Julia
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ström, Jakob O.
    Örebro University, Sweden.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Testosterone-like immunoreactivity in hair measured in minute sample amounts - a competitive radioimmunoassay with an adequate limit of detection2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 17636Article in journal (Refereed)
    Abstract [en]

    The concentrations of testosterone deposited in hair during hair growth may provide a retrospective reflection of the concentrations of bioactive testosterone in plasma. The objective of this study was to develop a radioimmunoassay with a sufficiently low limit of detection to measure the testosterone-like immunoreactivity in smaller hair samples (5 mg) than used in earlier studies, and to compare three different extraction procedures. The competitive radioimmunoassay consisted of a polyclonal antiserum (immunogen testosterone-7 alpha-BSA) and a radioligand synthesised from testosterone-3-CMO-histamine. The within-assay and total coefficients of variation in the working range was 3% and 4.5%, respectively. The limit of detection was 0.87 pg/mL, which is equivalent to 0.12 pg/mg testosterone in 5 mg of hair. The concentration of testosterone-like immunoreactivity in hair samples was 1.23 (SD 0.47) pg/mg in women and 2.67 (SD 0.58) pg/mg in men (pulverised hair). Significantly improved precision was found when pulverised hair was used compared to non-pulverised hair. Our data indicate that pulverisation of the hair prior to hormone extraction is crucial. Detection limits fit for the intended purpose are achievable with 5 mg samples of hair.

  • 178.
    Soares, Ana R. A.
    et al.
    Lund Univ, Sweden.
    Lapierre, Jean-Francois
    Univ Montreal, Canada.
    Panneer Selvam, Balathandayuthabani
    Linköping University, Department of Thematic Studies, Tema Environmental Change. Linköping University, Faculty of Arts and Sciences.
    Lindström, Göran
    Swedish Meteorol and Hydrol Inst, Sweden.
    Berggren, Martin
    Lund Univ, Sweden.
    Controls on Dissolved Organic Carbon Bioreactivity in River Systems2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 14897Article in journal (Refereed)
    Abstract [en]

    Inland waters transport, transform and retain significant amounts of dissolved organic carbon (DOC) that may be biologically reactive (bioreactive) and thus potentially degraded into atmospheric CO2. Despite its global importance, relatively little is known about environmental controls on bioreactivity of DOC as it moves through river systems with varying water residence time (WRT). Here we determined the influence ofWRT and landscape properties on DOC bioreactivity in 15 Swedish catchments spanning a large geographical and environmental gradient. We found that the short-term bioreactive pools (0-6 d of decay experiments) were linked to high aquatic primary productivity that, in turn, was stimulated by phosphorus loading from forested, agricultural and urban areas. Unexpectedly, the percentage of long-term bioreactive DOC (determined in 1-year experiments) increased with WRT, possibly due to photo-transformation of recalcitrant DOC from terrestrial sources into long-term bioreactive DOC with relatively lower aromaticity. Thus, despite overall decreases in DOC during water transit through the inland water continuum, DOC becomes relatively more bioreactive on a long time-scale. This increase in DOC bioreactivity with increasing WRT along the freshwater continuum has previously been overlooked. Further studies are needed to explain the processes and mechanisms behind this pattern on a molecular level.

  • 179.
    Sorensen, Line Bay
    et al.
    Aalborg Univ, Denmark.
    Gazerani, Parisa
    Aalborg Univ, Denmark.
    Wåhlén, Karin
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ghafouri, Nazdar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Investigation of biomarkers alterations after an acute tissue trauma in human trapezius muscle, using microdialysis2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 3034Article in journal (Refereed)
    Abstract [en]

    Alterations in muscle milieu are suggested as important activity of peripheral drive in patients with chronic musculoskeletal pain (CMP). Microdialysis (MD) has been used in monitoring altered metabolic response pattern in muscles. However, the insertion of MD probe causes a local tissue trauma. Whether and how metabolites in trapezius muscle are affected by acute tissue trauma is unknown. Hence, this study investigated the metabolic response and nociceptive reaction of the tissue following MD probe insertion in patients with CMP and healthy individuals. Fifty-nine patients and forty pain-free volunteers were recruited. Pressure pain thresholds (PPTs) were obtained at the trapezius and tibialis muscles. Pain questionnaires determined the levels of pain related aspects. MD (20 kDa cut-off) was performed in the trapezius and samples were collected within 40 min. Interstitial concentration of the metabolites was analyzed by a two-way-mixed-ANOVA. The metabolic response pattern changed over time and alterations in the level of metabolites could be seen in both CMP and healthy controls. Pain questionnaires and pain intensities manifested clinical aspects of pain closely to what CMP patients describe. Analyzing metabolites due to acute tissue trauma by aid of MD may be a useful model to investigate altered metabolic response effect in CMP.

  • 180.
    Stehr, Jan Eric
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Functional Electronic Materials. Linköping University, The Institute of Technology.
    Chen, Weimin
    Linköping University, Department of Physics, Chemistry and Biology, Functional Electronic Materials. Linköping University, The Institute of Technology.
    Koteeswawa Reddy, Nandanapalli
    Humboldt University, Institute of Chemistry, Berlin, Germany.
    Tu, Charles W.
    University of California, Department of Electrical and Computer Engineering, La Jolla, CA, USA.
    Buyanova, Irina
    Linköping University, Department of Physics, Chemistry and Biology, Functional Electronic Materials. Linköping University, The Institute of Technology.
    Efficient nitrogen incorporation in ZnO nanowires2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 13406Article in journal (Refereed)
    Abstract [en]

    One-dimensional ZnO nanowires (NWs) are a promising materials system for a variety of applications. Utilization of ZnO, however, requires a good understanding and control of material properties that are largely affected by intrinsic defects and contaminants. In this work we provide experimental evidence for unintentional incorporation of nitrogen in ZnO NWs grown by rapid thermal chemical vapor deposition, from electron paramagnetic resonance spectroscopy. The incorporated nitrogen atoms are concluded to mainly reside at oxygen sites (NO). The NO centers are suggested to be located in proximity to the NW surface, based on their reduced optical ionization energy as compared with that in bulk. This implies a lower defect formation energy at the NW surface as compared with its bulk value, consistent with theoretical predictions. The revealed facilitated incorporation of nitrogen in ZnO nanostructures may be advantageous for realizing p-type conducting ZnO via N doping. The awareness of this process can also help to prevent such unintentional doping in structures with desired n-type conductivity.

  • 181.
    Stehr, Jan Eric
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Surface Physics and Chemistry. Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Lundström, Ingemar
    Linköping University, Department of Physics, Chemistry and Biology, Sensor and Actuator Systems. Linköping University, Faculty of Science & Engineering.
    Karlsson, Jan Olof G.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Evidence that fodipir (DPDP) binds neurotoxic Pt2+ with a high affinity: An electron paramagnetic resonance study2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 15813Article in journal (Refereed)
    Abstract [en]

    Oxaliplatin typically causes acute neuropathic problems, which may, in a dose-dependent manner, develop into a chronic form of chemotherapy-induced peripheral neuropathy (CIPN), which is associated with retention of Pt2+ in the dorsal root ganglion. A clinical study by Coriat and co-workers suggests that co-treatment with mangafodipir [Manganese(II) DiPyridoxyl DiPhosphate; MnDPDP] cures ongoing CIPN. These authors anticipated that it is the manganese superoxide dismutase mimetic activity of MnDPDP that explains its curative activity. However, this is questionable from a pharmacokinetic perspective. Another, but until recently undisclosed possibility is that Pt2+ outcompetes Mn2+/Ca2+/Zn2+ for binding to DPDP or its dephosphorylated metabolite PLED (diPyridoxyL EthylDiamine) and transforms toxic Pt2+ into a non-toxic complex, which can be readily excreted from the body. We have used electron paramagnetic resonance guided competition experiments between MnDPDP (10logKML ≈ 15) and K2PtCl4, and between MnDPDP and ZnCl2 (10logKML ≈ 19), respectively, in order to obtain an estimate the 10logKML of PtDPDP. Optical absorption spectroscopy revealed a unique absorption line at 255 nm for PtDPDP. The experimental data suggest that PtDPDP has a higher formation constant than that of ZnDPDP, i.e., higher than 19. The present results suggest that DPDP/PLED has a high enough affinity for Pt2+ acting as an efficacious drug in chronic Pt2+-associated CIPN.

  • 182.
    Strauss, Timmy
    et al.
    Tech Univ Dresden, Germany.
    Kämpe, Robin
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Hamilton, Paul
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Olausson, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Rottstaedt, Fabian
    Tech Univ Dresden, Germany.
    Raue, Claudia
    Tech Univ Dresden, Germany.
    Croy, Ilona
    Tech Univ Dresden, Germany.
    Deactivation of default mode network during touch2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 1293Article in journal (Refereed)
    Abstract [en]

    Interpersonal touch possesses a strong affective component, which immediately evokes attention. The neural processing of such touch is moderated by specialized C-tactile nerve fibers in the periphery and results in central activation of somatosensory areas as well as regions involved in social processing, such as the superior temporal gyrus (STG). In the present functional neuroimaging investigation, we tested the hypothesis that the attention grasping effect of interpersonal touch as compared to impersonal touch is reflected in a more-pronounced deactivation of the default mode network (DMN). Using functional magnetic resonance imaging, we investigated the neural processing of interpersonal relative to impersonal touch conditions that were furthermore modulated by stroking velocity in order to target c-tactile nerve fibers to a different extent. A sample of 30 healthy participants (19 women, mean age 40.5 years) was investigated. In the impersonal touch, participants were stroked with a brush on the forearm. In the interpersonal touch condition, the experimenter performed the stroking with the palm of his hand. Interpersonal touch was rated as more pleasant and intense than impersonal touch and led to a stronger blood oxygen level dependent (BOLD) signal increase in the somatosensory cortex SII extending to the superior temporal cortex. Over all touch conditions, this activation was coupled in time to the deactivation of prominent nodes of the DMN. Although deactivation of the DMN was most pronounced for interpersonal touch conditions, the direct comparison did not show significant differences in DMN deactivation between interpersonal and impersonal touch or between different stroking velocities. We therefore conclude that all applied touch conditions deactivate the DMN and the strong connection to areas which code the contextual and social characteristics of affective touch may explain the attention grasping effect of touch.

  • 183.
    Ström, Jakob
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Ingberg, Edvin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Theodorsson, Annette
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Effects of high and low 17 beta-estradiol doses on focal cerebral ischemia: negative results2013In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 3Article in journal (Refereed)
    Abstract [en]

    The reasons why some animal studies indicate that estrogens increase focal cerebral ischemic damage while others show estrogen-induced neuroprotection has hitherto not been fully elucidated. Recent evidence indicates that discrepancies in hormone administration paradigms, resulting in highly different serum hormone concentrations, may account for the dichotomy. The current study aimed to test this hypothesis. Sixty ovariectomized female rats were randomized into three groups differing in 17 beta-estradiol regimens, and transient focal cerebral ischemia was subsequently induced. All animals were subjected to a small functional testing battery, and three days after MCAo they were sacrificed for infarct size assessment. Infarct sizes did not differ between groups, however clear discrepancies were seen in body weight and feeding behavior. In comparison to sham-operated animals, ovariectomized rats rapidly increased in body weight, whereas the opposite was seen in rats receiving 17beta-estradiol. The weight gain in the ovariectomized rats was paralleled by an increased food intake.

  • 184.
    Sundman, Ann-Sofie
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    van Poucke, Enya
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Svensson Holm, Ann-Charlotte
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Olsen Faresjö, Åshild
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Roth, Lina
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Long-term stress levels are synchronized in dogs and their owners2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 7391Article in journal (Refereed)
    Abstract [en]

    This study reveals, for the first time, an interspecific synchronization in long-term stress levels. Previously, acute stress, has been shown to be highly contagious both among humans and between individuals of other species. Here, long-term stress synchronization in dogs and their owners was investigated. We studied 58 dog-human dyads and analyzed their hair cortisol concentrations (HCC) at two separate occasions, reflecting levels during previous summer and winter months. The personality traits of both dogs and their owners were determined through owner-completed Dog Personality Questionnaire (DPQ) and human Big Five Inventory (BFI) surveys. In addition, the dogs activity levels were continuously monitored with a remote cloud-based activity collar for one week. Shetland sheepdogs (N = 33) and border collies (N = 25), balanced for sex, participated, and both pet dogs and actively competing dogs (agility and obedience) were included to represent different lifestyles. The results showed significant interspecies correlations in long-term stress where human HCC from both summer and winter samplings correlated strongly with dog HCC (summer: N = 57, chi(2) = 23.697, P amp;lt; 0.001, beta = 0.235; winter: N = 55, chi(2) = 13.796, P amp;lt; 0.001, beta = 0.027). Interestingly, the dogs activity levels did not affect HCC, nor did the amount of training sessions per week, showing that the HCC levels were not related to general physical activity. Additionally, there was a seasonal effect in HCC. However, although dogs personalities had little effects on their HCC, the human personality traits neuroticism, conscientiousness, and openness significantly affected dog HCC. Hence, we suggest that dogs, to a great extent, mirror the stress level of their owners.

  • 185.
    Säterberg, Torbjörn
    et al.
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering. Swedish Univ Agr Sci, Sweden.
    Jonsson, Tomas
    Swedish Univ Agr Sci, Sweden; Skovde Univ, Sweden.
    Yearsley, Jon
    Univ Coll Dublin, Ireland; UCD Earth Inst, Ireland.
    Berg, Sofia
    Skovde Univ, Sweden.
    Ebenman, Bo
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Biology. Linköping University, Faculty of Science & Engineering. Stockholm Univ, Sweden.
    A potential role for rare species in ecosystem dynamics2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 11107Article in journal (Refereed)
    Abstract [en]

    The ecological importance of common species for many ecosystem processes and functions is unquestionably due to their high a bundance.Yet, the importance of rare species is much less understood. Here we take a theoretical approach, exposing dynamical models of ecological networks to small perturbations, to explore the dynamical importance of rare and common species. We find that both species types contribute to the recovery of communities following generic perturbations (i.e. perturbations affecting all species).Yet, when perturbations are selective (i.e. affects only one species), perturbations to rare species have the most pronounced effect on community stability. We show that this is due to the strong indirect effects induced by perturbations to rare species. Because indirect effects typically set in at longer timescales, our results indicate that the importance of rare species may be easily overlooked and thus underrated. Hence, our study provides a potential ecological motive for the management and protection of rare species.

  • 186.
    Södergren, Anna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ramström, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Orebro Univ, Sweden.
    Platelet subpopulations remain despite strong dual agonist stimulation and can be characterised using a novel six-colour flow cytometry protocol2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 1441Article in journal (Refereed)
    Abstract [en]

    It is recognised that platelets respond differently to activation, where a subpopulation of platelets adopt a procoagulant phenotype while others are aggregatory. However, it has not been thoroughly tested whether these subpopulations will remain in maximally activated samples, or if they are merely a result of different platelet sensitivities to agonist activation. Here platelets were activated with gradually increasing concentrations of thrombin and/or the GPVI agonist cross-linked collagen-related peptide (CRP-XL). Platelet activation was investigated using a novel six-colour flow cytometry protocol evaluating exposure of phosphatidylserine, active conformation of the fibrinogen receptor alpha(IIb)beta(3), alpha-granule and lysosomal release (P-selectin and LAMP-1 exposure), mitochondrial membrane integrity and platelet fragmentation. Upon activation by CRP-XL or thrombin+CRP-XL, platelets formed three differently sized subpopulations. Normal-sized platelets showed high exposure of aggregatory active alpha(IIb)beta(3) and intact mitochondria, while the smaller platelets and platelet fragments showed high exposure of procoagulant phosphatidylserine. The distribution of platelets between the differently sized subpopulations remained stable despite high agonist concentrations. All three were still present after 30 and 60 min of activation, showing that all platelets will not have the same characteristics even after maximal stimulation. This suggests that platelet subpopulations with distinct activation patterns exist within the total platelet population.

  • 187.
    Tammimies, Kristiina
    et al.
    Karolinska Inst, Sweden.
    Li, Danyang
    Karolinska Inst, Sweden.
    Rabkina, Ielyzaveta
    Karolinska Inst, Sweden.
    Stamouli, Sofia
    Karolinska Inst, Sweden.
    Becker, Martin
    Karolinska Inst, Sweden.
    Nicolaou, Veronika
    Karolinska Inst, Sweden.
    Berggren, Steve
    Karolinska Inst, Sweden; Stockholm Hlth Serv, Sweden.
    Coco, Christina
    Karolinska Inst, Sweden; Stockholm Hlth Serv, Sweden.
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Curtin Univ, Australia.
    Jonsson, Ulf
    Karolinska Inst, Sweden; Stockholm Hlth Serv, Sweden; Uppsala Univ, Sweden.
    Choque-Olsson, Nora
    Karolinska Inst, Sweden.
    Bolte, Sven
    Karolinska Inst, Sweden; Stockholm Hlth Serv, Sweden; Curtin Univ, Australia.
    Association between Copy Number Variation and Response to Social Skills Training in Autism Spectrum Disorder2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 9810Article in journal (Refereed)
    Abstract [en]

    Challenges in social communication and interaction are core features of autism spectrum disorder (ASD) for which social skills group training (SSGT) is a commonly used intervention. SSGT has shown modest and heterogeneous effects. One of the major genetic risk factors in ASD is rare copy number variation (CNV). However, limited information exists whether CNV profiles could be used to aid intervention decisions. Here, we analyzed the rare genic CNV carrier status for 207 children, of which 105 received SSGT and 102 standard care as part of a randomized clinical trial for SSGT. We found that being a carrier of rare genic CNV did not have an impact on the SSGT outcome measured by the parent-report Social Responsiveness Scale (SRS). However, when stratifying by pathogenicity and size of the CNVs, we identified that carriers of clinically significant and large genic CNVs (amp;gt; 500 kb) showed inferior SRS outcomes at post-intervention (P = 0.047 and P = 0.036, respectively) and follow-up (P = 0.008 and P = 0.072, respectively) when adjusting for standard care effects. Our study provides preliminary evidence that carriers of clinically significant and large genic CNVs might not benefit as much from SSGT as non-carriers. Our results indicate that genetic information might help guide the modifications of interventions in ASD.

  • 188.
    Tobieson, Lovisa
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Zsigmond, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Rossitti, Sandro
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Hillman, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Marklund, Niklas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Lund Univ, Sweden.
    Dynamic protein changes in the perihaemorrhagic zone of Surgically Treated Intracerebral Haemorrhage Patients2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 3181Article in journal (Refereed)
    Abstract [en]

    The secondary injury cascades exacerbating the initial brain injury following intracerebral haemorrhage (ICH) are incompletely understood. We used dual microdialysis (MD) catheters placed in the perihaemorrhagic zone (PHZ) and in seemingly normal cortex (SNX) at time of surgical ICH evacuation in ten patients (range 26-70 years). Routine interstitial MD markers (including glucose and the lactate/pyruvate ratio) were analysed and remaining microdialysate was analysed by two-dimensional gel electrophoresis (2-DE) and nano-liquid chromatography tandem mass spectrometry (nLC-MS/MS). Two time intervals were analysed; median 2-10 hours post-surgery (time A) and median 68-76 hours post-ICH onset (time B). Using 2-DE, we quantified 232 +/- 31 different protein spots. Two proteins differed between the MD catheters at time A, and 12 proteins at time B (p amp;lt; 0.05). Thirteen proteins were significantly altered between time A and time B in the SNX and seven proteins in the PHZ, respectively. Using nLC-MS/MS ca 800 proteins were identified out of which 76 were present in all samples. At time A one protein was upregulated and two downregulated, and at time B, seven proteins were upregulated, and four downregulated in the PHZ compared to the SNX. Microdialysis-based proteomics is feasible for study of secondary injury mechanisms and discovery of biomarkers after ICH.

  • 189.
    Tollstoy Tegler, Lotta
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology. MIT, MA 02139 USA.
    Corin, Karolina
    MIT, MA 02139 USA; University of Witwatersrand, South Africa; University of Witwatersrand, South Africa.
    Hillger, Julia
    MIT, MA 02139 USA.
    Wassie, Brooke
    MIT, MA 02139 USA.
    Yu, Yanmei
    MIT, MA 02139 USA; Sichuan University, Peoples R China.
    Zhang, Shuguang
    MIT, MA 02139 USA.
    Cell-free expression, purification, and ligand-binding analysis of Drosophila melanogaster olfactory receptors DmOR67a, DmOR85b and DmORCO2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, no 7867Article in journal (Refereed)
    Abstract [en]

    Insects transmit numerous devastating diseases, including malaria, dengue fever, and sleeping sickness. Olfactory cues guide insects to their hosts, and are thus responsible for disease transmission. Understanding the molecular basis of insect olfaction could facilitate the development of interventions. The first step is to heterologously overexpress and purify insect olfactory receptors (ORs). This is challenging, as ORs are membrane proteins. Here, we show that insect ORs and their co-receptor can be expressed in an E. coli cell-free system. After immunoaffinity chromatography, the ORs are similar to 95% pure, and up to 1 mg/10 ml reaction is obtained. Circular dichroism together with microscale thermophoresis indicate that each receptor is properly folded, and can bind its respective ligand. This is the first time insect ORs have been expressed in an E. coli system. The methods described here could facilitate future structure-function studies, which may aid in developments to alleviate the suffering of millions caused by insect-transmitted diseases.

  • 190.
    Tong, Mancy
    et al.
    University of Auckland, New Zealand.
    Johansson, Caroline
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. University of Auckland, New Zealand.
    Xiao, Fengyi
    University of Auckland, New Zealand; Fudan University, Peoples R China.
    Stone, Peter R.
    University of Auckland, New Zealand.
    James, Joanna L.
    University of Auckland, New Zealand.
    Chen, Qi
    University of Auckland, New Zealand.
    Cree, Lynsey M.
    University of Auckland, New Zealand.
    Chamley, Lawrence W.
    University of Auckland, New Zealand.
    Antiphospholipid antibodies increase the levels of mitochondrial DNA in placental extracellular vesicles: Alarmin-g for preeclampsia2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 16556Article in journal (Refereed)
    Abstract [en]

    The pathogenesis of preeclampsia remains unclear but placental factors are known to play a crucial role causing maternal endothelial cell dysfunction. One potential factor is placental micro-and nano-vesicles. Antiphospholipid antibodies (aPL) increase the risk of preeclampsia ten-fold, in part by damaging the mitochondria in the syncytiotrophoblast. Since mitochondrial DNA (mtDNA) is a danger-associated molecular pattern (DAMP/alarmin) that may activate endothelial cells, the aims of the current study were to investigate whether aPL affect the number of placental vesicles extruded, their mtDNA content and their ability to activate endothelial cells. Exposure of first trimester human placental explants to aPL affected neither the number nor size of extruded micro-and nano-vesicles (n = 5), however their levels of mtDNA were increased (n = 6). These vesicles significantly activated endothelial cells (n = 5), which was prevented by blocking toll-like receptor 9 (TLR-9), a receptor for extracellular DNA. Thus, aPL may increase the risk of preeclampsia in part by increasing the amount of mtDNA associated with placental vesicles. That mitochondrial DNA is recognised as a DAMP by TLR-9 to cause endothelial cell activation, raises the possibility that placental vesicles or TLR-9 might be a target for pharmaceutical intervention to reduce the consequences of aPL in pregnancy.

  • 191.
    Turkina, Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Ghafouri, Nazdar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Evaluation of dynamic changes in interstitial fluid proteome following microdialysis probe insertion trauma in trapezius muscle of healthy women2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 43512Article in journal (Refereed)
    Abstract [en]

    Microdialysis ( MD) has been shown to be a promising technique for sampling of biomarkers. Implantation of MD probe causes an acute tissue trauma and provokes innate response cascades. In order to normalize tissue a two hours equilibration period for analysis of small molecules has been reported previously. However, how the proteome profile changes due to this acute trauma has yet to be fully understood. To characterize the early proteome events induced by this trauma we compared proteome in muscle dialysate collected during the equilibration period with two hours later in "post-trauma". Samples were collected from healthy females using a 100 kDa MW cut off membrane and analyzed by high sensitive liquid chromatography tandem mass spectrometry. Proteins involved in stress response, immune system processes, inflammatory responses and nociception from extracellular and intracellular fluid spaces were identified. Sixteen proteins were found to be differentially abundant in samples collected during first two hours in comparison to "post-trauma". Our data suggests that microdialysis in combination with mass spectrometry may provide potentially new insights into the interstitial proteome of trapezius muscle, yet should be further adjusted for biomarker discovery and diagnostics. Moreover, MD proteome alterations in response to catheter injury may reflect individual innate reactivity.

  • 192.
    Tybrandt, Klas
    et al.
    Institute for Biomedical Engineering ETH Zurich, Zurich Switzerland.
    Stauffer, Flurin
    Institute for Biomedical Engineering ETH Zurich, Zurich Switzerland.
    Vörös, Janos
    Institute for Biomedical Engineering ETH Zurich, Zurich Switzerland.
    Multilayer Patterning of High Resolution Intrinsically Stretchable Electronics2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, p. 1-6, article id 25641Article in journal (Refereed)
    Abstract [en]

    Stretchable electronics can bridge the gap between hard planar electronic circuits and the curved, soft and elastic objects of nature. This has led to applications like conformal displays, electronic skin and soft neuroprosthetics. A remaining challenge, however, is to match the dimensions of the interfaced systems, as all require feature sizes well below 100 μm. Intrinsically stretchable nanocomposites are attractive in this context as the mechanical deformations occur on the nanoscale, although methods for patterning high performance materials have been lacking. Here we address these issues by reporting on a multilayer additive patterning approach for high resolution fabrication of stretchable electronic devices. The method yields highly conductive 30 μm tracks with similar performance to their macroscopic counterparts. Further, we demonstrate a three layer micropatterned stretchable electroluminescent display with pixel sizes down to 70 μm. These presented findings pave the way towards future developments of high definition displays, electronic skins and dense multielectrode arrays.

  • 193.
    Urbano Alves, Pedro
    et al.
    University of Nova Lisboa, Portugal; CEMOP UNINOVA, Portugal.
    Vinhas, Raquel
    University of Nova Lisboa, Portugal.
    Fernandes, Alexandra R.
    University of Nova Lisboa, Portugal.
    Zuhal Birol, Semra
    Istanbul Technical University, Turkey.
    Trabzon, Levent
    Istanbul Technical University, Turkey.
    Bernacka-Wojcik, Iwona
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering. University of Nova Lisboa, Portugal; CEMOP UNINOVA, Portugal.
    Igreja, Rui
    University of Nova Lisboa, Portugal; CEMOP UNINOVA, Portugal.
    Lopes, Paulo
    University of Aveiro, Portugal; University of Aveiro, Portugal.
    Viana Baptista, Pedro
    University of Nova Lisboa, Portugal.
    Aguas, Hugo
    University of Nova Lisboa, Portugal; CEMOP UNINOVA, Portugal.
    Fortunato, Elvira
    University of Nova Lisboa, Portugal; CEMOP UNINOVA, Portugal.
    Martins, Rodrigo
    University of Nova Lisboa, Portugal; CEMOP UNINOVA, Portugal.
    Multifunctional microfluidic chip for optical nanoprobe based RNA detection - application to Chronic Myeloid Leukemia2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 381Article in journal (Refereed)
    Abstract [en]

    Many diseases have their treatment options narrowed and end up being fatal if detected during later stages. As a consequence, point-of-care devices have an increasing importance for routine screening applications in the health sector due to their portability, fast analyses and decreased cost. For that purpose, a multifunctional chip was developed and tested using gold nanoprobes to perform RNA optical detection inside a microfluidic chip without the need of molecular amplification steps. As a proof-of-concept, this device was used for the rapid detection of chronic myeloid leukemia, a hemato-oncological disease that would benefit from early stage diagnostics and screening tests. The chip passively mixed target RNA from samples, gold nanoprobes and saline solution to infer a result from their final colorimetric properties. An optical fiber network was used to evaluate its transmitted spectra inside the chip. Trials provided accurate output results within 3 min, yielding signal-to-noise ratios up to 9 dB. When compared to actual state-of-art screening techniques of chronic myeloid leukemia, these results were, at microscale, at least 10 times faster than the reported detection methods for chronic myeloid leukemia. Concerning point-of-care applications, this work paves the way for other new and more complex versions of optical based genosensors.

  • 194.
    Uziela, Karolis
    et al.
    Stockholm University, Sweden.
    Shu, Nanjiang
    Stockholm University, Sweden; Science Life Lab, Sweden.
    Wallner, Björn
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Elofsson, Arne
    Stockholm University, Sweden.
    ProQ3: Improved model quality assessments using Rosetta energy terms2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 33509Article in journal (Refereed)
    Abstract [en]

    Quality assessment of protein models using no other information than the structure of the model itself has been shown to be useful for structure prediction. Here, we introduce two novel methods, ProQRosFA and ProQRosCen, inspired by the state-of-art method ProQ2, but using a completely different description of a protein model. ProQ2 uses contacts and other features calculated from a model, while the new predictors are based on Rosetta energies: ProQRosFA uses the full-atom energy function that takes into account all atoms, while ProQRosCen uses the coarse-grained centroid energy function. The two new predictors also include residue conservation and terms corresponding to the agreement of a model with predicted secondary structure and surface area, as in ProQ2. We show that the performance of these predictors is on par with ProQ2 and significantly better than all other model quality assessment programs. Furthermore, we show that combining the input features from all three predictors, the resulting predictor ProQ3 performs better than any of the individual methods. ProQ3, ProQRosFA and ProQRosCen are freely available both as a webserver and stand-alone programs at http://proq3.bioinfo.se/.

  • 195.
    Vasefi, Fartash
    et al.
    Spectral Molecular Imaging Inc., 250 N. Robertson Blvd., Beverly Hills CA, USA.
    MacKinnon, Nicholas
    Spectral Molecular Imaging Inc., 250 N. Robertson Blvd., Beverly Hills CA, USA.
    Saager, Rolf B.
    Beckman Laser Institute and Medical Clinic, University of California, Irvine, 1002 Health Sciences Rd. East, Irvine, CA, USA.
    Durkin, Anthony J.
    Beckman Laser Institute and Medical Clinic, University of California, Irvine, 1002 Health Sciences Rd. East, Irvine, CA, USA.
    Chave, Robert
    Spectral Molecular Imaging Inc., 250 N. Robertson Blvd., Beverly Hills CA, USA.
    Lindsley, Erik H.
    Spectral Molecular Imaging Inc., 250 N. Robertson Blvd., Beverly Hills CA, USA.
    Farkas, Daniel L.
    Spectral Molecular Imaging Inc., 250 N. Robertson Blvd., Beverly Hills CA, USA / Department of Biomedical Engineering, University of Southern California, Los Angeles CA, USA.
    Polarization-Sensitive Hyperspectral Imaging in vivo: A Multimode Dermoscope for Skin Analysis2014In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 4, no 1, article id 4924Article in journal (Refereed)
    Abstract [en]

    Attempts to understand the changes in the structure and physiology of human skin abnormalities by non-invasive optical imaging are aided by spectroscopic methods that quantify, at the molecular level, variations in tissue oxygenation and melanin distribution. However, current commercial and research systems to map hemoglobin and melanin do not correlate well with pathology for pigmented lesions or darker skin. We developed a multimode dermoscope that combines polarization and hyperspectral imaging with an efficient analytical model to map the distribution of specific skin bio-molecules. This corrects for the melanin-hemoglobin misestimation common to other systems, without resorting to complex and computationally intensive tissue optical models. For this system's proof of concept, human skin measurements on melanocytic nevus, vitiligo, and venous occlusion conditions were performed in volunteers. The resulting molecular distribution maps matched physiological and anatomical expectations, confirming a technologic approach that can be applied to next generation dermoscopes and having biological plausibility that is likely to appeal to dermatologists.

  • 196.
    Verma, Deepti
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Ramanarao Parasa, Venkata
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Raffetseder, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Martis, Mihaela-Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Bhai Mehta, Ratnesh
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Netea, Mihai
    Radboud University of Nijmegen, Netherlands.
    Lerm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Anti-mycobacterial activity correlates with altered DNA methylation pattern in immune cells from BCG-vaccinated subjects2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 12305Article in journal (Refereed)
    Abstract [en]

    The reason for the largely variable protective effect against TB of the vaccine Bacille Calmette-Guerin (BCG) is not understood. In this study, we investigated whether epigenetic mechanisms are involved in the response of immune cells to the BCG vaccine. We isolated peripheral blood mononuclear cells (PBMCs) from BCG-vaccinated subjects and performed global DNA methylation analysis in combination with functional assays representative of innate immunity against Mycobacterium tuberculosis infection. Enhanced containment of replication was observed in monocyte-derived macrophages from a subgroup of BCG-vaccinated individuals (identified as responders). A stable and robust differential DNA methylation pattern in response to BCG could be observed in PBMCs isolated from the responders but not from the non-responders. Gene ontology analysis revealed that promoters with altered DNA methylation pattern were strongly enriched among genes belonging to immune pathways in responders, however no enrichments could be observed in the non-responders. Our findings suggest that BCG-induced epigenetic reprogramming of immune cell function can enhance anti-mycobacterial immunity in macrophages. Understanding why BCG induces this response in responders but not in nonresponders could provide clues to improvement of TB vaccine efficacy.

  • 197.
    Vlaic, Sebastian
    et al.
    Leibniz Inst Nat Prod Res and Infect Biol, Germany.
    Conrad, Theresia
    Leibniz Inst Nat Prod Res and Infect Biol, Germany.
    Tokarski-Schnelle, Christian
    Leibniz Inst Nat Prod Res and Infect Biol, Germany.
    Gustafsson, Mika
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Dahmen, Uta
    Friedrich Schiller Univ, Germany.
    Guthke, Reinhard
    Leibniz Inst Nat Prod Res and Infect Biol, Germany.
    Schuster, Stefan
    Friedrich Schiller Univ, Germany.
    ModuleDiscoverer: Identification of regulatory modules in protein-protein interaction networks2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 433Article in journal (Refereed)
    Abstract [en]

    The identification of disease-associated modules based on protein-protein interaction networks (PPINs) and gene expression data has provided new insights into the mechanistic nature of diverse diseases. However, their identification is hampered by the detection of protein communities within large-scale, whole-genome PPINs. A presented successful strategy detects a PPINs community structure based on the maximal clique enumeration problem (MCE), which is a non-deterministic polynomial time-hard problem. This renders the approach computationally challenging for large PPINs implying the need for new strategies. We present ModuleDiscoverer, a novel approach for the identification of regulatory modules from PPINs and gene expression data. Following the MCE-based approach, ModuleDiscoverer uses a randomization heuristic-based approximation of the community structure. Given a PPIN of Rattus norvegicus and public gene expression data, we identify the regulatory module underlying a rodent model of non-alcoholic steatohepatitis (NASH), a severe form of non-alcoholic fatty liver disease (NAFLD). The module is validated using single-nucleotide polymorphism (SNP) data from independent genome-wide association studies and gene enrichment tests. Based on gene enrichment tests, we find that ModuleDiscoverer performs comparably to three existing module-detecting algorithms. However, only our NASH-module is significantly enriched with genes linked to NAFLD-associated SNPs. ModuleDiscoverer is available at http://www.hki-jene.de/index.php/0/2/490 (Others/ModuleDiscoverer).

  • 198.
    Wang, Chao
    et al.
    Umeå Univ, Sweden.
    Iashchishyn, Igor A.
    Umeå Univ, Sweden; Sumy State Univ, Ukraine.
    Pansieri, Jonathan
    Umeå Univ, Sweden.
    Nyström, Sofie
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Klementieva, Oxana
    Lund Univ, Sweden.
    Kara, John
    Umea Univ, Sweden.
    Horvath, Istvan
    Umea Univ, Sweden.
    Moskalenko, Roman
    Umea Univ, Sweden; Sumy State Univ, Ukraine.
    Rofougaran, Reza
    Umea Univ, Sweden.
    Gouras, Gunnar
    Lund Univ, Sweden.
    Kovacs, Gabor G.
    Med Univ Vienna, Austria.
    Shankar, S. K.
    Natl Inst Mental Hlth and Neurosci, India.
    Morozova-Roche, Ludmilla A.
    Umea Univ, Sweden.
    S100A9-Driven Amyloid-Neuroinflammatory Cascade in Traumatic Brain Injury as a Precursor State for Alzheimers Disease2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 12836Article in journal (Refereed)
    Abstract [en]

    Pro-inflammatory and amyloidogenic S100A9 protein is an important contributor to Alzheimers disease (AD) pathology. Traumatic brain injury (TBI) is viewed as a precursor state for AD. Here we have shown that S100A9-driven amyloid-neuroinflammatory cascade was initiated in TBI and may serve as a mechanistic link between TBI and AD. By analyzing the TBI and AD human brain tissues, we demonstrated that in post-TBI tissues S100A9, produced by neurons and microglia, becomes drastically abundant compared to A beta and contributes to both precursor-plaque formation and intracellular amyloid oligomerization. Conditions implicated in TBI, such as elevated S100A9 concentration, acidification and fever, provide strong positive feedback for S100A9 nucleation-dependent amyloid formation and delay in its proteinase clearance. Consequently, both intracellular and extracellular S100A9 oligomerization correlated with TBI secondary neuronal loss. Common morphology of TBI and AD plaques indicated their similar initiation around multiple aggregation centers. Importantly, in AD and TBI we found S100A9 plaques without A beta. S100A9 and A beta plaque pathology was significantly advanced in AD cases with TBI history at earlier age, signifying TBI as a risk factor. These new findings highlight the detrimental consequences of prolonged post-TBI neuroinflammation, which can sustain S100A9-driven amyloid-neurodegenerative cascade as a specific mechanism leading to AD development.

  • 199.
    Wang, Mo-Jin
    et al.
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Sichuan University, Peoples R China.
    Ping, Jie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Li, Yuan
    Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Adell, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Nodin, Bjorn
    Lund University, Sweden.
    Meng, Wen-Jian
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Zhang, Hong
    University of Örebro, Sweden.
    Yu, Yong-Yang
    Sichuan University, Peoples R China.
    Wang, Cun
    Sichuan University, Peoples R China.
    Yang, Lie
    Sichuan University, Peoples R China.
    Zhou, Zong-Guang
    Sichuan University, Peoples R China.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    The prognostic factors and multiple biomarkers in young patients with colorectal cancer2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, no 10645Article in journal (Refereed)
    Abstract [en]

    The incidence of colorectal cancer (CRC) in young patients (less than= 50 years of age) appears to be increasing. However, their clinicopathological characteristics and survival are controversial. Likewise, the biomarkers are unclear. We used the West China (2008-2013, China), Surveillance, Epidemiology, and End Results program (1973-2011, United States) and Linkoping Cancer (1972-2009, Sweden) databases to analyse clinicopathological characteristics, survival and multiple biomarkers of young CRC patients. A total of 509,934 CRC patients were included from the three databases. The young CRC patients tended to have more distal location tumours, fewer tumour numbers, later stage, more mucinous carcinoma and poorer differentiation. The cancer-specific survival (CSS) of young patients was significantly better. The PRL (HR = 12.341, 95% CI = 1.615-94.276, P = 0.010), RBM3 (HR = 0.093, 95% CI = 0.012-0.712, P = 0.018), Wrap53 (HR = 1.952, 95% CI = 0.452-6.342, P = 0.031), p53 (HR = 5.549, 95% CI = 1.176-26.178, P = 0.045) and DNA status (HR = 17.602, 95% CI = 2.551-121.448, P = 0.001) were associated with CSS of the young patients. In conclusion, this study suggests that young CRC patients present advanced tumours and more malignant pathological features, while they have a better prognosis. The PRL, RBM3, Wrap53, p53 and DNA status are potential prognostic biomarkers for the young CRC patients.

  • 200.
    Wang, Xin
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Mazurkiewicz, Magdalena
    Karolinska Institute, Sweden.
    Hillert, Ellin-Kristina
    Karolinska Institute, Sweden.
    Hägg Olofsson, Maria
    Karolinska Institute, Sweden.
    Pierrou, Stefan
    ESP Life Science Consulting AB, Sweden.
    Hillertz, Per
    Biosynchro West AB, Sweden.
    Gullbo, Joachim
    Uppsala University, Sweden.
    Selvaraju, Karthik
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Drug Research.
    Paulus, Aneel
    Mayo Clin, FL 32224 USA.
    Akhtar, Sharoon
    Mayo Clin, FL 32224 USA.
    Bossler, Felicitas
    DKFZ, Germany.
    Chanan Khan, Asher
    Mayo Clin, FL 32224 USA; Mayo Clin, FL 32224 USA.
    Linder, Stig
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Cancer Center Karolinska, Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden.
    D´arcy, Padraig
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    The proteasome deubiquitinase inhibitor VLX1570 shows selectivity for ubiquitin-specific protease-14 and induces apoptosis of multiple myeloma cells2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, p. 1-14, article id 26979Article in journal (Refereed)
    Abstract [en]

    Inhibition of deubiquitinase (DUB) activity is a promising strategy for cancer therapy. VLX1570 is an inhibitor of proteasome DUB activity currently in clinical trials for relapsed multiple myeloma. Here we show that VLX1570 binds to and inhibits the activity of ubiquitin-specific protease-14 (USP14) in vitro, with comparatively weaker inhibitory activity towards UCHL5 (ubiquitin-C-terminal hydrolase-5). Exposure of multiple myeloma cells to VLX1570 resulted in thermostabilization of USP14 at therapeutically relevant concentrations. Transient knockdown of USP14 or UCHL5 expression by electroporation of siRNA reduced the viability of multiple myeloma cells. Treatment of multiple myeloma cells with VLX1570 induced the accumulation of proteasome-bound high molecular weight polyubiquitin conjugates and an apoptotic response. Sensitivity to VLX1570 was moderately affected by altered drug uptake, but was unaffected by overexpression of BCL2-family proteins or inhibitors of caspase activity. Finally, treatment with VLX1570 was found to lead to extended survival in xenograft models of multiple myeloma. Our findings demonstrate promising antiproliferative activity of VLX1570 in multiple myeloma, primarily associated with inhibition of USP14 activity.

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