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  • 1.
    Aad, G.
    et al.
    Aix Marseille Univ, CPPM, CNRS IN2P3, Marseille, France..
    Leopold, Alexander
    KTH, School of Engineering Sciences (SCI), Physics, Particle and Astroparticle Physics.
    Lundberg, Olof
    KTH, School of Engineering Sciences (SCI), Physics, Particle and Astroparticle Physics.
    Lund-Jensen, Bengt
    KTH, School of Engineering Sciences (SCI), Physics, Particle and Astroparticle Physics.
    Ohm, Christian
    KTH, School of Engineering Sciences (SCI), Physics, Particle and Astroparticle Physics.
    Ripellino, Giulia
    KTH, School of Engineering Sciences (SCI), Physics, Particle and Astroparticle Physics.
    Shaheen, Rabia
    KTH, School of Engineering Sciences (SCI), Physics, Particle and Astroparticle Physics.
    Shope, David R.
    KTH, School of Engineering Sciences (SCI), Physics, Particle and Astroparticle Physics.
    Strandberg, Jonas
    KTH, School of Engineering Sciences (SCI), Physics, Particle and Astroparticle Physics.
    Zwalinski, L.
    CERN, Geneva, Switzerland..
    et al.,
    Search for invisible Higgs-boson decays in events with vector-boson fusion signatures using 139 fb(-1) of proton-proton data recorded by the ATLAS experiment2022In: Journal of High Energy Physics (JHEP), ISSN 1126-6708, E-ISSN 1029-8479, no 8, article id 104Article in journal (Refereed)
    Abstract [en]

    A direct search for Higgs bosons produced via vector-boson fusion and subsequently decaying into invisible particles is reported. The analysis uses 139 fb(-1) of pp collision data at a centre-of-mass energy of root s =13 TeV recorded by the ATLAS detector at the LHC. The observed numbers of events are found to be in agreement with the background expectation from Standard Model processes. For a scalar Higgs boson with a mass of 125 GeV and a Standard Model production cross section, an observed upper limit of 0.145 is placed on the branching fraction of its decay into invisible particles at 95% confidence level, with an expected limit of 0.103. These results are interpreted in the context of models where the Higgs boson acts as a portal to dark matter, and limits are set on the scattering cross section of weakly interacting massive particles and nucleons. Invisible decays of additional scalar bosons with masses from 50 GeV to 2 TeV are also studied, and the derived upper limits on the cross section times branching fraction decrease with increasing mass from 1.0 pb for a scalar boson mass of 50 GeV to 0.1 pb at a mass of 2 TeV.

  • 2. Aaldering, L. J.
    et al.
    Poongavanam, V.
    Langkjær, N.
    Natarajan Arul, Murugan
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Jørgensen, P. T.
    Wengel, J.
    Veedu, R. N.
    Development of an Efficient G-Quadruplex-Stabilised Thrombin-Binding Aptamer Containing a Three-Carbon Spacer Molecule2017In: ChemBioChem (Print), ISSN 1439-4227, E-ISSN 1439-7633, Vol. 18, no 8, p. 755-763Article in journal (Refereed)
    Abstract [en]

    The thrombin-binding aptamer (TBA), which shows anticoagulant properties, is one of the most studied G-quadruplex-forming aptamers. In this study, we investigated the impact of different chemical modifications such as a three-carbon spacer (spacer-C3), unlocked nucleic acid (UNA) and 3′-amino-modified UNA (amino-UNA) on the structural dynamics and stability of TBA. All three modifications were incorporated at three different loop positions (T3, T7, T12) of the TBA G-quadruplex structure to result in a series of TBA variants and their stability was studied by thermal denaturation; folding was studied by circular dichroism spectroscopy and thrombin clotting time. The results showed that spacer-C3 introduction at the T7 loop position (TBA-SP7) significantly improved stability and thrombin clotting time while maintaining a similar binding affinity as TBA to thrombin. Detailed molecular modelling experiments provided novel insights into the experimental observations, further supporting the efficacy of TBA-SP7. The results of this study could provide valuable information for future designs of TBA analogues with superior thrombin inhibition properties. 

  • 3.
    AbdElKhalek, Y. M.
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS).
    Awad, M. I.
    Abd El Munim, H. E.
    Maged, S. A.
    Trajectory-based fast ball detection and tracking for an autonomous industrial robot system2021In: International Journal of Intelligent Systems Technologies and Applications, ISSN 1740-8865, E-ISSN 1740-8873, Vol. 20, no 2, p. 126-145Article in journal (Refereed)
    Abstract [en]

    Autonomising industrial robots is the main goal in this paper; imagine humanoid robots that have several degrees of freedom (DOF) mechanisms as their arms. What if the humanoid's arms could be programmed to be responsive to their surrounding environment, without any hard-coding assigned? This paper presents the idea of an autonomous system, where the system observes the surrounding environment and takes action on its observation. The application here is that of rebuffing an object that is thrown towards a robotic arm's workspace. This application mimics the idea of high dynamic responsiveness of a robot's arm. This paper will present a trajectory generation framework for rebuffing incoming flying objects. The framework bases its assumptions on inputs acquired through image processing and object detection. After extensive testing, it can be said that the proposed framework managed to fulfil the real-time system requirements for this application, with an 80% successful rebuffing rate. 

  • 4.
    Abdellah, Tebani
    et al.
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology.
    Gummesson, Anders
    Zhong, Wen
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Koistinen, Ina Schuppe
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lakshmikanth, Tadepally
    Olsson, Lisa M.
    Boulund, Fredrik
    Neiman, Maja
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Stenlund, Hans
    Hellström, Cecilia
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Karlsson, Max
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Arif, Muhammad
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Dodig-Crnkovic, Tea
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Mardinoglu, Adil
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology. Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London, England.
    Lee, Sunjae
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Zhang, Cheng
    Chen, Yang
    Olin, Axel
    Mikes, Jaromir
    Danielsson, Hanna
    von Feilitzen, Kalle
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Jansson, Per-Anders
    Angerås, Oskar
    Huss, Mikael
    Kjellqvist, Sanela
    Odeberg, Jacob
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Edfors, Fredrik
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology.
    Tremaroli, Valentina
    Forsström, Björn
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology.
    Schwenk, Jochen M.
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics.
    Nilsson, Peter
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics.
    Moritz, Thomas
    Bäckhed, Fredrik
    Engstrand, Lars
    Brodin, Petter
    Bergström, Göran
    Uhlén, Mathias
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology. Danish Tech Univ, Ctr Biosustainabil, Copenhagen, Denmark.
    Fagerberg, Linn
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology.
    Integration of molecular profiles in a longitudinal wellness profiling cohort2020In: Nature Communications, E-ISSN 2041-1723, Vol. 11, no 1, article id 4487Article in journal (Refereed)
  • 5. Abelein, Axel
    et al.
    Lang, Lisa
    Lendel, Christofer
    Gräslund, Astrid
    Danielsson, Jens
    Transient small molecule interactions kinetically modulate amyloid β peptide self-assembly.2012In: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 586, no 22, p. 3991-3995, article id S0014-5793(12)00757-0Article in journal (Refereed)
    Abstract [en]

    Small organic molecules, like Congo red and lacmoid, have been shown to modulate the self-assembly of the amyloid β peptide (Aβ). Here, we show that Aβ forms NMR invisible non-toxic co-aggregates together with lacmoid as well as Congo red. We find that the interaction involves two distinct kinetic processes and at every given time point only a small fraction of Aβ is in the co-aggregate. These weak transient interactions kinetically redirect the aggregation prone Aβ from self-assembling into amyloid fibrils. These findings suggest that even such weak binders might be effective as therapeutics against pathogenic protein aggregation.

  • 6. Abi-Rached, Laurent
    et al.
    Jobin, Matthew J.
    Kulkarni, Subhash
    McWhinnie, Alasdair
    Dalva, Klara
    Gragert, Loren
    Babrzadeh, Farbod
    Stanford University, United States .
    Gharizadeh, Baback
    Luo, Ma
    Plummer, Francis A.
    Kimani, Joshua
    Carrington, Mary
    Middleton, Derek
    Rajalingam, Raja
    Beksac, Meral
    Marsh, Steven G. E.
    Maiers, Martin
    Guethlein, Lisbeth A.
    Tavoularis, Sofia
    Little, Ann-Margaret
    Green, Richard E.
    Norman, Paul J.
    Parham, Peter
    The Shaping of Modern Human Immune Systems by Multiregional Admixture with Archaic Humans2011In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 334, no 6052, p. 89-94Article in journal (Refereed)
    Abstract [en]

    Whole genome comparisons identified introgression from archaic to modern humans. Our analysis of highly polymorphic human leukocyte antigen (HLA) class I, vital immune system components subject to strong balancing selection, shows how modern humans acquired the HLA-B*73 allele in west Asia through admixture with archaic humans called Denisovans, a likely sister group to the Neandertals. Virtual genotyping of Denisovan and Neandertal genomes identified archaic HLA haplotypes carrying functionally distinctive alleles that have introgressed into modern Eurasian and Oceanian populations. These alleles, of which several encode unique or strong ligands for natural killer cell receptors, now represent more than half the HLA alleles of modern Eurasians and also appear to have been later introduced into Africans. Thus, adaptive introgression of archaic alleles has significantly shaped modern human immune systems.

  • 7.
    Abouzayed, A.
    et al.
    Uppsala Univ, Uppsala, Sweden..
    Rinne, S. S.
    Uppsala Univ, Uppsala, Sweden..
    Wadeea, F.
    Uppsala Univ, Uppsala, Sweden..
    Tano, Hanna
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Protein Engineering.
    Nagy, Abel
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Eriksson Karlström, Amelie
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Protein Engineering.
    Tolmachev, V.
    Uppsala Univ, Uppsala, Sweden..
    Orlova, A.
    Uppsala Univ, Uppsala, Sweden..
    Conjugation of GRPR-targeting antagonist RM26 to albumin-binding domain extends antagonist's blood circulation and residence in tumours2020In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 47, no SUPPL 1, p. S652-S652Article in journal (Other academic)
  • 8. Abrahamsson, T. R.
    et al.
    Jakobsson, H. E.
    Andersson, Anders F.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Björkstén, B.
    Engstrand, Lars
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Jenmalm, M. C.
    Low gut microbiota diversity in early infancy precedes asthma at school age2014In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 44, no 6, p. 842-850Article in journal (Refereed)
    Abstract [en]

    Background Low total diversity of the gut microbiota during the first year of life is associated with allergic diseases in infancy, but little is known how early microbial diversity is related to allergic disease later in school age. Objective To assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to the prevalence of different allergic diseases in school age, such as asthma, allergic rhinoconjunctivitis (ARC) and eczema. Methods The microbial diversity and composition was analysed with barcoded 16S rDNA 454 pyrosequencing in stool samples at 1week, 1month and 12months of age in 47 infants which were subsequently assessed for allergic disease and skin prick test reactivity at 7years of age (ClinicalTrials.gov ID NCT01285830). Results Children developing asthma (n=8) had a lower diversity of the total microbiota than non-asthmatic children at 1week (P=0.04) and 1month (P=0.003) of age, whereas allergic rhinoconjunctivitis (n=13), eczema (n=12) and positive skin prick reactivity (n=14) at 7years of age did not associate with the gut microbiota diversity. Neither was asthma associated with the microbiota composition later in infancy (at 12months). Children having IgE-associated eczema in infancy and subsequently developing asthma had lower microbial diversity than those that did not. There were no significant differences, however, in relative abundance of bacterial phyla and genera between children with or without allergic disease. Conclusion and Clinical Relevance Low total diversity of the gut microbiota during the first month of life was associated with asthma but not ARC in children at 7years of age. Measures affecting microbial colonization of the infant during the first month of life may impact asthma development in childhood.

  • 9. Abrahamsson, Thomas R.
    et al.
    Jakobsson, Hedvig E.
    Andersson, Anders F.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Björksten, Bengt
    Engstrand, Lars
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Jenmalm, Maria C.
    Gut microbiota diversity and atopic disease: Does breast-feeding play a role? Reply2013In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 131, no 1, p. 248-249Article in journal (Other academic)
  • 10.
    Abrami, Laurence
    et al.
    Ecole Polytech Fed Lausanne, Global Hlth Inst, Sch Life Sci, Lausanne, Switzerland..
    Audagnotto, Martina
    Ecole Polytech Fed Lausanne, Inst Bioengn, Sch Life Sci, Lausanne, Switzerland..
    Ho, Sylvia
    Ecole Polytech Fed Lausanne, Global Hlth Inst, Sch Life Sci, Lausanne, Switzerland..
    Marcaida, Maria Jose
    Ecole Polytech Fed Lausanne, Inst Bioengn, Sch Life Sci, Lausanne, Switzerland..
    Mesquita, Francisco S.
    Ecole Polytech Fed Lausanne, Global Hlth Inst, Sch Life Sci, Lausanne, Switzerland..
    Anwar, Muhammad U.
    Ecole Polytech Fed Lausanne, Global Hlth Inst, Sch Life Sci, Lausanne, Switzerland..
    Sandoz, Patrick
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biophysics. KTH, Centres, Science for Life Laboratory, SciLifeLab. Ecole Polytech Fed Lausanne, Global Hlth Inst, Sch Life Sci, Lausanne, Switzerland..
    Fonti, Giulia
    Ecole Polytech Fed Lausanne, Inst Bioengn, Sch Life Sci, Lausanne, Switzerland..
    Pojer, Florence
    Ecole Polytech Fed Lausanne, Sch Life Sci, Prot Prod & Struct Core Facil, Lausanne, Switzerland..
    Dal Peraro, Matteo
    Ecole Polytech Fed Lausanne, Inst Bioengn, Sch Life Sci, Lausanne, Switzerland..
    van der Goot, F. Gisou
    Ecole Polytech Fed Lausanne, Global Hlth Inst, Sch Life Sci, Lausanne, Switzerland..
    Palmitoylated acyl protein thioesterase APT2 deforms membranes to extract substrate acyl chains2021In: Nature Chemical Biology, ISSN 1552-4450, E-ISSN 1552-4469, Vol. 17, no 4, p. 438-U173Article in journal (Refereed)
    Abstract [en]

    Acyl protein thioesterase APT2 interacts with membranes via its charged beta-tongue, becomes palmitoylated by ZDHHC3/7 and deforms the bilayer to extract substrate acyl chains. APT2 deacylation leads to its membrane release and degradation. Many biochemical reactions require controlled recruitment of proteins to membranes. This is largely regulated by posttranslational modifications. A frequent one is S-acylation, which consists of the addition of acyl chains and can be reversed by poorly understood acyl protein thioesterases (APTs). Using a panel of computational and experimental approaches, we dissect the mode of action of the major cellular thioesterase APT2 (LYPLA2). We show that soluble APT2 is vulnerable to proteasomal degradation, from which membrane binding protects it. Interaction with membranes requires three consecutive steps: electrostatic attraction, insertion of a hydrophobic loop and S-acylation by the palmitoyltransferases ZDHHC3 or ZDHHC7. Once bound, APT2 is predicted to deform the lipid bilayer to extract the acyl chain bound to its substrate and capture it in a hydrophobic pocket to allow hydrolysis. This molecular understanding of APT2 paves the way to understand the dynamics of APT2-mediated deacylation of substrates throughout the endomembrane system.

  • 11. Abrams, M. B.
    et al.
    Bjaalie, J. G.
    Das, S.
    Egan, G. F.
    Ghosh, S. S.
    Goscinski, W. J.
    Grethe, J. S.
    Hellgren Kotaleski, Jeanette
    KTH, School of Electrical Engineering and Computer Science (EECS), Computer Science, Computational Science and Technology (CST).
    Ho, E. T. W.
    Kennedy, D. N.
    Lanyon, L. J.
    Leergaard, T. B.
    Mayberg, H. S.
    Milanesi, L.
    Mouček, R.
    Poline, J. B.
    Roy, P. K.
    Strother, S. C.
    Tang, T. B.
    Tiesinga, P.
    Wachtler, T.
    Wójcik, D. K.
    Martone, M. E.
    A Standards Organization for Open and FAIR Neuroscience: the International Neuroinformatics Coordinating Facility2021In: Neuroinformatics, ISSN 1539-2791, E-ISSN 1559-0089Article in journal (Refereed)
    Abstract [en]

    There is great need for coordination around standards and best practices in neuroscience to support efforts to make neuroscience a data-centric discipline. Major brain initiatives launched around the world are poised to generate huge stores of neuroscience data. At the same time, neuroscience, like many domains in biomedicine, is confronting the issues of transparency, rigor, and reproducibility. Widely used, validated standards and best practices are key to addressing the challenges in both big and small data science, as they are essential for integrating diverse data and for developing a robust, effective, and sustainable infrastructure to support open and reproducible neuroscience. However, developing community standards and gaining their adoption is difficult. The current landscape is characterized both by a lack of robust, validated standards and a plethora of overlapping, underdeveloped, untested and underutilized standards and best practices. The International Neuroinformatics Coordinating Facility (INCF), an independent organization dedicated to promoting data sharing through the coordination of infrastructure and standards, has recently implemented a formal procedure for evaluating and endorsing community standards and best practices in support of the FAIR principles. By formally serving as a standards organization dedicated to open and FAIR neuroscience, INCF helps evaluate, promulgate, and coordinate standards and best practices across neuroscience. Here, we provide an overview of the process and discuss how neuroscience can benefit from having a dedicated standards body.

  • 12. Adhikari, P. R.
    et al.
    Upadhyaya, B. B.
    Meng, Chen
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Hollmén, J.
    Gene selection in time-series gene expression data2011In: 6th IAPR International Conference on Pattern Recognition in Bioinformatics, PRIB 2011, 2011, p. 145-156Conference paper (Refereed)
    Abstract [en]

    The dimensionality of biological data is often very high. Feature selection can be used to tackle the problem of high dimensionality. However, majority of the work in feature selection consists of supervised feature selection methods which require class labels. The problem further escalates when the data is time-series gene expression measurements that measure the effect of external stimuli on biological system. In this paper we propose an unsupervised method for gene selection from time-series gene expression data founded on statistical significance testing and swap randomization. We perform experiments with a publicly available mouse gene expression dataset and also a human gene expression dataset describing the exposure to asbestos. The results in both datasets show a considerable decrease in number of genes.

  • 13. Adhikari, Subash
    et al.
    Uhlén, Mathias
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology.
    Baker, Mark S.
    A high-stringency blueprint of the human proteome2020In: Nature Communications, E-ISSN 2041-1723, Vol. 11, no 1, article id 5301Article in journal (Refereed)
    Abstract [en]

    The Human Proteome Organization (HUPO) launched the Human Proteome Project (HPP) in 2010, creating an international framework for global collaboration, data sharing, quality assurance and enhancing accurate annotation of the genome-encoded proteome. During the subsequent decade, the HPP established collaborations, developed guidelines and metrics, and undertook reanalysis of previously deposited community data, continuously increasing the coverage of the human proteome. On the occasion of the HPP's tenth anniversary, we here report a 90.4% complete high-stringency human proteome blueprint. This knowledge is essential for discerning molecular processes in health and disease, as we demonstrate by highlighting potential roles the human proteome plays in our understanding, diagnosis and treatment of cancers, cardiovascular and infectious diseases. The Human Proteome Project (HPP) was launched in 2010 to enhance accurate annotation of the genome-encoded proteome. Ten years later, the HPP releases its first blueprint of the human proteome, annotating 90% of all known proteins at high-stringency and discussing the implications of proteomics for precision medicine.

  • 14.
    Adlerz, Ellen
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Sortase A coupling of the recombinant partial silk proteins 4Rep-Srt and G-/G5-CT to understand the structure of silk fiber2023Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Spider silk is a material of interest due its biocompatibility and therefore usage as a biomaterial. Its comparability to man-made materials in terms of strength and elasticity, along its biocompatibility, makes it desirable in the medical field. Dragline silk is one of seven types of silk made by orb-web-weaving spiders which is used as a lifeline in case of predators to escape and is therefore very strong and extensible. The dragline silk is composed of two proteins, called major ampullate spidroin silk protein 1 and 2 (MaSp1 & 2) since it is made in the major ampullate gland in the spider. These two proteins are in turn composed of three parts, a repetitive region in the middle, and two nonrepetitive regions at the terminals, N- and C-terminal domain. Having spiders as main producers of silk when conducting research come with difficulties and have made researchers turn to recombinant production for expression, mostly in E. coli. However, the protein size is a limitation when expressing in E. coli so researchers has come up with a smaller protein than MaSp made up of only the repetitive region and the C-terminal domain, called 4RepCT. 4RepCT is still able to self-assemble into fibers under physiological-like conditions and is biocompatible. 4RepCT can be functionalized with other biomolecules that can alter its function, e.g., a cell-adhesion motif from fibronectin, allowing 4RepCT to bind to cells. In this project we aim to produce 4Rep-Srt and G-/G5-CT separately before coupling them with enzyme Sortase A. Sortase A recognizes a Sortase tag (LPXTG) on the C-terminus of one protein (4Rep-Srt in this project) and connects it to another protein that has 1-5 glycine’s on the N-terminus (G-/G5-CT in this project). When producing the proteins separately, we can express G-/G5-CT with 13C and 15N before coupling and then know which part of the 4Rep-G-/G5-CT protein is G-/G5-CT. By knowing the structure of the protein, protein features and functions can be discovered to better aid the engineering of proteins to get biomolecules with wanted functions.

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  • 15. Adori, Csaba
    et al.
    Barde, Swapnali
    Vas, Szilvia
    Ebner, Karl
    Su, Jie
    Svensson, Camilla
    Mathé, Aleksander A.
    Singewald, Nicolas
    Reinscheid, Rainer R.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Kultima, Kim
    Bagdy, Gyorgy
    Hökfelt, Tomas
    Exploring the role of neuropeptide S in the regulation of arousal: a functional anatomical study2016In: Brain Structure and Function, ISSN 1863-2653, E-ISSN 1863-2661, Vol. 221, no 7, p. 3521-3546Article in journal (Refereed)
    Abstract [en]

    Neuropeptide S (NPS) is a regulatory peptide expressed by limited number of neurons in the brainstem. The simultaneous anxiolytic and arousal-promoting effect of NPS suggests an involvement in mood control and vigilance, making the NPS-NPS receptor system an interesting potential drug target. Here we examined, in detail, the distribution of NPS-immunoreactive (IR) fiber arborizations in brain regions of rat known to be involved in the regulation of sleep and arousal. Such nerve terminals were frequently apposed to GABAergic/galaninergic neurons in the ventro-lateral preoptic area (VLPO) and to tyrosine hydroxylase-IR neurons in all hypothalamic/thalamic dopamine cell groups. Then we applied the single platform-on-water (mainly REM) sleep deprivation method to study the functional role of NPS in the regulation of arousal. Of the three pontine NPS cell clusters, the NPS transcript levels were increased only in the peri-coerulear group in sleep-deprived animals, but not in stress controls. The density of NPS-IR fibers was significantly decreased in the median preoptic nucleus-VLPO region after the sleep deprivation, while radioimmunoassay and mass spectrometry measurements showed a parallel increase of NPS in the anterior hypothalamus. The expression of the NPS receptor was, however, not altered in the VLPO-region. The present results suggest a selective activation of one of the three NPS-expressing neuron clusters as well as release of NPS in distinct forebrain regions after sleep deprivation. Taken together, our results emphasize a role of the peri-coerulear cluster in the modulation of arousal, and the importance of preoptic area for the action of NPS on arousal and sleep.

  • 16. Aebersold, Ruedi
    et al.
    Agar, Jeffrey N.
    Amster, I. Jonathan
    Baker, Mark S.
    Bertozzi, Carolyn R.
    Boja, Emily S.
    Costello, Catherine E.
    Cravatt, Benjamin F.
    Fenselau, Catherine
    Garcia, Benjamin A.
    Ge, Ying
    Gunawardena, Jeremy
    Hendrickson, Ronald C.
    Hergenrother, Paul J.
    Huber, Christian G.
    Ivanov, Alexander R.
    Jensen, Ole N.
    Jewett, Michael C.
    Kelleher, Neil L.
    Kiessling, Laura L.
    Krogan, Nevan J.
    Larsen, Martin R.
    Loo, Joseph A.
    Loo, Rachel R. Ogorzalek
    Lundberg, Emma
    KTH, Centres, Science for Life Laboratory, SciLifeLab. Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
    MacCoss, Michael J.
    Mallick, Parag
    Mootha, Vamsi K.
    Mrksich, Milan
    Muir, Tom W.
    Patrie, Steven M.
    Pesavento, James J.
    Pitteri, Sharon J.
    Rodriguez, Henry
    Saghatelian, Alan
    Sandoval, Wendy
    Schluter, Hartmut
    Sechi, Salvatore
    Slavoff, Sarah A.
    Smith, Lloyd M.
    Snyder, Michael P.
    Thomas, Paul M.
    Uhlen, Mathias
    Van Eyk, Jennifer E.
    Vidal, Marc
    Walt, David R.
    White, Forest M.
    Williams, Evan R.
    Wohlschlager, Therese
    Wysocki, Vicki H.
    Yates, Nathan A.
    Young, Nicolas L.
    Zhang, Bing
    How many human proteoforms are there?2018In: Nature Chemical Biology, ISSN 1552-4450, E-ISSN 1552-4469, Vol. 14, no 3, p. 206-214Article in journal (Refereed)
    Abstract [en]

    Despite decades of accumulated knowledge about proteins and their post-translational modifications (PTMs), numerous questions remain regarding their molecular composition and biological function. One of the most fundamental queries is the extent to which the combinations of DNA-, RNA-and PTM-level variations explode the complexity of the human proteome. Here, we outline what we know from current databases and measurement strategies including mass spectrometry-based proteomics. In doing so, we examine prevailing notions about the number of modifications displayed on human proteins and how they combine to generate the protein diversity underlying health and disease. We frame central issues regarding determination of protein-level variation and PTMs, including some paradoxes present in the field today. We use this framework to assess existing data and to ask the question, "How many distinct primary structures of proteins (proteoforms) are created from the 20,300 human genes?" We also explore prospects for improving measurements to better regularize protein-level biology and efficiently associate PTMs to function and phenotype.

  • 17.
    Agaton, Charlotta
    et al.
    KTH, Superseded Departments (pre-2005), Biotechnology.
    Uhlén, Mathias
    KTH, Superseded Departments (pre-2005), Biotechnology.
    Hober, Sophia
    KTH, Superseded Departments (pre-2005), Biotechnology.
    Genome-based proteomics2004In: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 25, no 9, p. 1280-1288Article in journal (Refereed)
    Abstract [en]

    Protein-protein interactions play crucial roles in various biological pathways and functions. Therefore, the characterization of protein levels and also the network of interactions within an organism would contribute considerably to the understanding of life. The availability of the human genome sequence has created a range of new possibilities for biomedical research. A crucial challenge is to utilize the genetic information for better understanding of protein distribution and function in normal as well as in pathological biological processes. In this review, we have focused on different platforms used for systematic genome-based proteome analyses. These technologies are in many ways complementary and should be seen as various ways to elucidate different functions of the proteome.

  • 18.
    Agerstrand, Marlene
    et al.
    KTH, School of Architecture and the Built Environment (ABE), Philosophy and History of Technology, Philosophy.
    Kuester, A.
    Bachmann, J.
    Breitholtz, M.
    Ebert, I.
    Rechenberg, B.
    Ruden, Christina
    KTH, School of Architecture and the Built Environment (ABE), Philosophy and History of Technology, Philosophy.
    Reporting and evaluation criteria as means towards a transparent use of ecotoxicity data for environmental risk assessment of pharmaceuticals2011In: Environmental Pollution, ISSN 0269-7491, E-ISSN 1873-6424, Vol. 159, no 10, p. 2487-2492Article in journal (Refereed)
    Abstract [en]

    Ecotoxicity data with high reliability and relevance are needed to guarantee the scientific quality of environmental risk assessments of pharmaceuticals. The main advantages of a more structured approach to data evaluation include increased transparency and predictability of the risk assessment process, and the possibility to use non-standard data. In this collaboration, between the research project MistraPharma and the German Federal Environment Agency, a new set of reporting and evaluation criteria is presented and discussed. The new criteria are based on the approaches in the literature and the OECD reporting requirements, and have been further developed to include both reliability and relevance of test data. Intended users are risk assessors and researchers performing ecotoxicological experiments, but the criteria can also be used for education purposes and in the peer-review process for scientific papers. This approach intends to bridge the gap between the regulator and the scientist's needs and way of work.

  • 19.
    Agliari, Elena
    et al.
    Dipartimento di Fisica, Universita` degli Studi di Parma, viale G. Usberti 7, 43100 Parma, Italy.
    Barra, Adriano
    Del Ferraro, Gino
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Guerra, Francesco
    Tantari, Daniele
    Anergy in self-directed B lymphocytes: A statistical mechanics perspective2013In: Journal of Theoretical Biology, ISSN 0022-5193, E-ISSN 1095-8541, Vol. 375, p. 21-31Article in journal (Refereed)
    Abstract [en]

    Self-directed lymphocytes may evade clonal deletion at ontogenesis but still remain harmless due to a mechanism called clonal anergy. For B-lymphocytes, two major explanations for anergy developed over the last decades: according to Varela theory, anergy stems from a proper orchestration of the whole B-repertoire, such that self-reactive clones, due to intensive feed-back from other clones, display strong inertia when mounting a response. Conversely, according to the model of cognate response, self-reacting cells are not stimulated by helper lymphocytes and the absence of such signaling yields anergy. Through statistical mechanics we show that helpers do not prompt activation of a sub-group of B-cells: remarkably, the latter are just those broadly interacting in the idiotypic network. Hence Varela theory can finally be reabsorbed into the prevailing framework of the cognate response model. Further, we show how the B-repertoire architecture may emerge, where highly connected clones are self-directed as a natural consequence of ontogenetic learning. 

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  • 20. Agnarsdottir, Margret
    et al.
    Sooman, Linda
    Bolander, Asa
    Stromberg, Sara
    Rexhepaj, Elton
    Bergqvist, Michael
    Ponten, Fredrik
    Gallagher, William
    Lennartsson, Johan
    Ekman, Simon
    Uhlen, Mathias
    KTH, School of Biotechnology (BIO), Proteomics. KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Hedstrand, Hakan
    SOX10 expression in superficial spreading and nodular malignant melanomas2010In: Melanoma research, ISSN 0960-8931, E-ISSN 1473-5636, Vol. 20, no 6, p. 468-478Article in journal (Refereed)
    Abstract [en]

    SOX10 is a transcription factor expressed in nerve cells and melanocytes. The aim of this study was to investigate the protein expression pattern of SOX10 in malignant melanoma tumors and to analyze whether the results correlated with clinical parameters and the proliferation marker Ki-67. Furthermore, proliferation and migration were analyzed in three different cell lines employing SOX10 small interfering RNA-mediated silencing. Expression patterns were determined in 106 primary tumors and 39 metastases in addition to 16 normal skin samples and six benign nevi employing immunohistochemistry and tissue microarrays. The immunohistochemical staining was evaluated manually and with an automated algorithm. SOX10 was strongly expressed in the benign tissues, but for the malignant tumors superficial spreading melanomas stained stronger than nodular malignant melanomas (P = 0.008). The staining intensity was also inversely correlated with T-stage (Spearman's rho = -0.261, P = 0.008). Overall survival and time to recurrence were significantly correlated with SOX10 intensity, but not in multivariate analysis including T-stage. With the automated algorithm there was an inverse correlation between the SOX10 staining intensity and the proliferation marker, Ki-67 (rho = -0.173, P = 0.02) and a significant difference in the intensity signal between the benign tissues, the primary tumors and the metastases where the metastases stained the weakest (P <= 0.001). SOX10 downregulation resulted in variable effects on proliferation and migration rates in the melanoma cell lines. In conclusion, the SOX10 intensity level differed depending on the tissue studied and SOX10 might have a role in survival. No conclusion regarding the role of SOX10 for in-vitro proliferation and migration could be drawn. Melanoma Res 20:468-478

  • 21. Agostinho, A.
    et al.
    Kouznetsova, A.
    Hernández-Hernández, A.
    Bernhem, Kristoffer
    KTH, School of Engineering Sciences (SCI), Applied Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Blom, Hans
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biophysics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biophysics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Höög, C.
    Sexual dimorphism in the width of the mouse synaptonemal complex2018In: Journal of Cell Science, ISSN 0021-9533, E-ISSN 1477-9137, Vol. 131, no 5, article id jcs212548Article in journal (Refereed)
    Abstract [en]

    Sexual dimorphism has been used to describe morphological differences between the sexes, but can be extended to any biologically related process that varies between males and females. The synaptonemal complex (SC) is a tripartite structure that connects homologous chromosomes in meiosis. Here, aided by superresolution microscopy techniques, we show that the SC is subject to sexual dimorphism, in mouse germ cells. We have identified a significantly narrower SC in oocytes and have established that this difference does not arise from a different organization of the lateral elements nor from a different isoform of transverse filament protein SYCP1. Instead, we provide evidence for the existence of a narrower central element and a different integration site for the C-termini of SYCP1, in females. In addition to these female-specific features, we speculate that post-translation modifications affecting the SYCP1 coiled-coil region could render a more compact conformation, thus contributing to the narrower SC observed in females.

  • 22. Agostinho, Ana
    et al.
    Manneberg, Otto
    KTH, School of Engineering Sciences (SCI), Applied Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    van Schendel, Robin
    Hernandez-Hernandez, Abrahan
    Kouznetsova, Anna
    Blom, Hans
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Höög, Christer
    High density of REC8 constrains sister chromatid axes and prevents illegitimate synaptonemal complex formation2016In: EMBO Reports, ISSN 1469-221X, E-ISSN 1469-3178, Vol. 17, no 6, p. 901-913Article in journal (Refereed)
    Abstract [en]

    During meiosis, cohesin complexes mediate sister chromatid cohesion (SCC), synaptonemal complex (SC) assembly and synapsis. Here, using super-resolution microscopy, we imaged sister chromatid axes in mouse meiocytes that have normal or reduced levels of cohesin complexes, assessing the relationship between localization of cohesin complexes, SCC and SC formation. We show that REC8 foci are separated from each other by a distance smaller than 15% of the total chromosome axis length in wild-type meiocytes. Reduced levels of cohesin complexes result in a local separation of sister chromatid axial elements (LSAEs), as well as illegitimate SC formation at these sites. REC8 but not RAD21 or RAD21L cohesin complexes flank sites of LSAEs, whereas RAD21 and RAD21L appear predominantly along the separated sister-chromatid axes. Based on these observations and a quantitative distribution analysis of REC8 along sister chromatid axes, we propose that the high density of randomly distributed REC8 cohesin complexes promotes SCC and prevents illegitimate SC formation.

  • 23.
    Ahlgren, Kajsa
    et al.
    Chalmers Univ Technol, Dept Phys, Div Nanobiophys, SE-41296 Gothenburg, Sweden..
    Olsson, Christoffer
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Medical Imaging.
    Ermilova, Inna
    Chalmers Univ Technol, Dept Phys, Div Nanobiophys, SE-41296 Gothenburg, Sweden..
    Swenson, Jan
    Chalmers Univ Technol, Dept Phys, Div Nanobiophys, SE-41296 Gothenburg, Sweden..
    New insights into the protein stabilizing effects of trehalose by comparing with sucrose2023In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 25, no 32, p. 21215-21226Article in journal (Refereed)
    Abstract [en]

    Disaccharides are well known to be efficient stabilizers of proteins, for example in the case of lyophilization or cryopreservation. However, although all disaccharides seem to exhibit bioprotective and stabilizing properties, it is clear that trehalose is generally superior compared to other disaccharides. The aim of this study was to understand this by comparing how the structural and dynamical properties of aqueous trehalose and sucrose solutions influence the protein myoglobin (Mb). The structural studies were based on neutron and X-ray diffraction in combination with empirical potential structure refinement (EPSR) modeling, whereas the dynamical studies were based on quasielastic neutron scattering (QENS) and molecular dynamics (MD) simulations. The results show that the overall differences in the structure and dynamics of the two systems are small, but nevertheless there are some important differences which may explain the superior stabilizing effects of trehalose. It was found that in both systems the protein is preferentially hydrated by water, but that this effect is more pronounced for trehalose, i.e. trehalose forms less hydrogen bonds to the protein surface than sucrose. Furthermore, the rotational motion around dihedrals between the two glucose rings of trehalose is slower than in the case of the dihedrals between the glucose and fructose rings of sucrose. This leads to a less perturbed protein structure in the case of trehalose. The observations indicate that an aqueous environment closest to the protein molecules is beneficial for an efficient bioprotective solution.

  • 24. Ahmadian, Afshin
    et al.
    Pettersson, Erik
    Lundeberg, Joakim
    KTH, School of Biotechnology (BIO), Gene Technology.
    Method for amplification2005Patent (Other (popular science, discussion, etc.))
    Abstract [en]

    The invention refers to a method for multiplex amplification of at least one specific nucleic acid locus, comprising the steps of: providing at least one oligonucleotide probe pair that is designed so that the first and second probe of the pair anneal to a specific nucleic acid locus on a target molecule, in which pair the first probe has an extendable 3'-end, and a second probe has a 5'-end that is directly or indirectly labelled with a phosphate group; providing a target molecule comprising at least one specific nucleic acid locus; allowing the probe pair to anneal to the target molecule; allowing the 3'-end of the first probe to extend by influence of polymerase by adding a set of three different dNTPs; ligating the 3'-end of the extended first probe to the 5'-end of the second probe. Hereby, a method is provided which allows a high specificity for simultaneous amplification of several loci. Further, the invention involves a kit for use in the method of the invention.

  • 25.
    Ahrenstedt, Lage
    KTH, School of Biotechnology (BIO).
    Surface modification of cellulose materials: from wood pulps to artificial blood vessels2007Licentiate thesis, comprehensive summary (Other scientific)
    Abstract [en]

    This thesis describes the improvement of two radically different cellulose materials, paper and artificial blood vessels, constructed from two diverse cellulose sources, wood pulp and Acetobacter xylinum. The improvement of both materials was possible due to the natural affinity of the hemicellulose xyloglucan for cellulose.

    Chemical and mechanical pulps were treated with xyloglucan in the wet-end prior to hand sheet formation or by spray application of dry hand sheets, loading a comparable amount of xyloglucan. The tensile strength increases for the wet-end treatment and spray application were 28% and 71% respectively for bleached soft wood, compared to untreated sheets (20.7 Nm/g). The corresponding strength increases for hand sheets made of thermo-mechanical pulp were 6% and 13% respectively compared to untreated sheets (42.4 Nm/g). The tendency for chemical pulp to be superior to mechanical pulp with respect to strength increase was valid even for tear strength and Scott-Bond. These results suggest, in agreement with other studies, that adhesion of xyloglucan to wood fibres is dependent on their degree of surface lignification.

    Also, a method was developed to increase the blood compatibility of artificial blood vessels constructed of bacterial cellulose. Xyloglucan was covalently linked to the endothelial cell adhesion motif (Arg-Gly-Asp). To obtain this, new solid-phase coupling chemistry was developed. Xyloglucan oligosaccharides (XGO) were transformed into XGO-succinamic acid via the corresponding XGO--NH2 derivative prior to coupling with the N-terminus of the solid-phase synthesised Gly-Arg-Gly-Asp-Ser peptide. The resin-bound glyco-peptide was then cleaved and enzymatically re-incorporated into high molecular weight xyloglucan. The glyco-peptide was further adsorbed onto bacterial cellulose scaffolds, increasing the adhesion and proliferation of endothelial cells and therefore blood compatibility.

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  • 26.
    Akander, Amanda
    KTH, School of Biotechnology (BIO).
    Massive parallell DNA-sequencing - future methods to obtain a human genome in 15 minutes2014Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
  • 27. Akhi, Ramin
    et al.
    Wang, Chunguang
    Kyrklund, Mikael
    Kummu, Outi
    Turunen, Sini Pauliina
    Univ Oulu, Oulu.
    Hyvärinen, Kati
    Kullaa, Arja
    Salo, Tuula
    Pussinen, Pirkko J
    Hörkkö, Sohvi
    Cross-reactive saliva IgA antibodies to oxidized LDL and periodontal pathogens in humans.2017In: Journal of Clinical Periodontology, ISSN 0303-6979, E-ISSN 1600-051X, Vol. 44, no 7, p. 682-691Article in journal (Refereed)
    Abstract [en]

    AIM: Oxidized low-density lipoproteins (oxLDL) are formed as a result of lipid peroxidation and are highly immunogenic and proatherogenic. In this study, saliva antibodies binding to oxLDL, Porphyromonas gingivalis (Pg) and Aggregatibacter actinomycetemcomitans (Aa) were characterized and their cross-reactivity was evaluated.

    MATERIALS AND METHODS: Resting and stimulated saliva samples were collected from 36 healthy adults (mean age 26 years). Saliva IgA, IgG and IgM autoantibody levels to copper oxidized LDL (CuOx-LDL) and malondialdehyde acetaldehyde-modified LDL (MAA-LDL) were determined with chemiluminescence immunoassay.

    RESULTS: Saliva IgA and IgG antibodies binding to MAA-LDL and CuOx-LDL were detected in all samples and they were associated with the saliva levels of IgA and IgG to P. gingivalis and A. actinomycetemcomitans. Competitive immunoassay showed that saliva antibodies to MAA-LDL cross-reacted specifically with P. gingivalis. The autoantibody levels to oxLDL in saliva were not associated with the autoantibody levels to oxLDL in plasma or with saliva apolipoprotein B 100 levels.

    CONCLUSIONS: Saliva contains IgA and IgG binding to oxLDL, which showed cross-reactive properties with the periodontal pathogens Porphyromonas gingivalis (P.g). The data suggest that secretory IgA to P.g may participate in immune reactions involved in LDL oxidation through molecular mimicry.

  • 28.
    Akhras, Michael S.
    KTH, School of Biotechnology (BIO).
    Nucleic Acid Based Pathogen Diagnostics2008Doctoral thesis, comprehensive summary (Other scientific)
    Abstract [en]

    Pathogenic organisms are transmitted to the host organism through all possible connected pathways, and cause a myriad of diseases states. Commonly occurring curable infectious diseases still impose the greatest health impacts on a worldwide perspective. The Bill & Melinda Gates Foundation partnered with RAND Corporation to form the Global Health Diagnostics Forum, with the goal of establishing and interpreting mathematical models for what effects a newly introduced point-of-care pathogen diagnostic would have in developing countries. The results were astonishing, with potentially millions of lives to be saved on an annual basis.

    Golden standard for diagnostics of pathogenic bacteria has long been cultureable medias. Environmental biologists have estimated that less than 1% of all bacteria are cultureable. Genomic-based approaches offer the potential to identify all microbes from all the biological kingdoms. Nucleic acid based pathogen diagnostics has evolved significantly over the past decades. Novel technologies offer increased potential in sensitivity, specificity, decreased costs and parallel sample management. However, most methods are confined to core laboratory facilities. To construct an ultimate nucleic acid based diagnostic for use in areas of need, potential frontline techniques need to be identified and combined.

    The research focus of this doctoral thesis work has been to develop and apply nucleic acid based methods for pathogen diagnostics. Methods and assays were applied to the two distinct systems i) screening for antibiotic resistance mutations in the bacterial pathogen Neisseria gonorrhoeae, and ii) genotype determination of the cancer causative Human Papillomavirus (HPV). The first part of the study included development of rapid, direct and multiplex Pyrosequencing nucleic acid screenings. With improved methodology in the sample preparation process, we could detect an existence of multiple co-infecting HPV genotypes at greater sensitivities than previously described, when using the same type of methodology. The second part of the study focused on multiplex nucleic acid amplification strategies using Molecular Inversion Probes with end-step Pyrosequencing screening. The PathogenMip assay presents a complete detection schematic for virtually any known pathogenic organism. We also introduce the novel Connector Inversion Probe, a padlock probe capable of complete gap-fill reactions for multiplex nucleic acid amplifications.

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  • 29. Akhter, S.
    et al.
    Westrin, Karl Johan
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Zivi, N.
    Nordal, V.
    Kretzschmar, Warren W.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Delhomme, N.
    Street, N. R.
    Nilsson, O.
    Emanuelsson, Olof
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology.
    Sundström, J. F.
    Cone-setting in spruce is regulated by conserved elements of the age-dependent flowering pathway2022In: New Phytologist, ISSN 0028-646X, E-ISSN 1469-8137, Vol. 236, no 5, p. 1951-1963Article in journal (Refereed)
    Abstract [en]

    Reproductive phase change is well characterized in angiosperm model species, but less studied in gymnosperms. We utilize the early cone-setting acrocona mutant to study reproductive phase change in the conifer Picea abies (Norway spruce), a gymnosperm. The acrocona mutant frequently initiates cone-like structures, called transition shoots, in positions where wild-type P. abies always produces vegetative shoots. We collect acrocona and wild-type samples, and RNA-sequence their messenger RNA (mRNA) and microRNA (miRNA) fractions. We establish gene expression patterns and then use allele-specific transcript assembly to identify mutations in acrocona. We genotype a segregating population of inbred acrocona trees. A member of the SQUAMOSA BINDING PROTEIN-LIKE (SPL) gene family, PaSPL1, is active in reproductive meristems, whereas two putative negative regulators of PaSPL1, miRNA156 and the conifer specific miRNA529, are upregulated in vegetative and transition shoot meristems. We identify a mutation in a putative miRNA156/529 binding site of the acrocona PaSPL1 allele and show that the mutation renders the acrocona allele tolerant to these miRNAs. We show co-segregation between the early cone-setting phenotype and trees homozygous for the acrocona mutation. In conclusion, we demonstrate evolutionary conservation of the age-dependent flowering pathway and involvement of this pathway in regulating reproductive phase change in the conifer P. abies. 

  • 30.
    Akhter, Shirin
    et al.
    Swedish Univ Agr Sci, Linnean Ctr Plant Biol, Uppsala Bioctr, Dept Plant Biol, Uppsala, Sweden..
    Kretzschmar, Warren W.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Nordal, Veronika
    Swedish Univ Agr Sci, Linnean Ctr Plant Biol, Uppsala Bioctr, Dept Plant Biol, Uppsala, Sweden..
    Delhomme, Nicolas
    Swedish Univ Agr Sci, Dept Forest Genet & Plant Physiol, Umea Plant Sci Ctr, Umea, Sweden..
    Street, Nathaniel R.
    Umea Sweden, Dept Plant Physiol, Umea Plant Sci Ctr, Umea, Sweden..
    Nilsson, Ove
    Swedish Univ Agr Sci, Dept Forest Genet & Plant Physiol, Umea Plant Sci Ctr, Umea, Sweden..
    Emanuelsson, Olof
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Sundström, Jens F.
    Swedish Univ Agr Sci, Linnean Ctr Plant Biol, Uppsala Bioctr, Dept Plant Biol, Uppsala, Sweden..
    Integrative Analysis of Three RNA Sequencing Methods Identifies Mutually Exclusive Exons of MADS-Box Isoforms During Early Bud Development in Picea abies2018In: Frontiers in Plant Science, E-ISSN 1664-462X, Vol. 9, article id 1625Article in journal (Refereed)
    Abstract [en]

    Recent efforts to sequence the genomes and transcriptomes of several gymnosperm species have revealed an increased complexity in certain gene families in gymnosperms as compared to angiosperms. One example of this is the gymnosperm sister Glade to angiosperm TM3-like MADS-box genes, which at least in the conifer lineage has expanded in number of genes. We have previously identified a member of this subclade, the conifer gene DEFICIENS AGAMOUS LIKE 19 (DAL19), as being specifically upregulated in cone-setting shoots. Here, we show through Sanger sequencing of mRNA-derived cDNA and mapping to assembled conifer genomic sequences that DAL19 produces six mature mRNA splice variants in Picea abies. These splice variants use alternate first and last exons, while their four central exons constitute a core region present in all six transcripts. Thus, they are likely to be transcript isoforms. Quantitative Real-Time PCR revealed that two mutually exclusive first DAL19 exons are differentially expressed across meristems that will form either male or female cones, or vegetative shoots. Furthermore, mRNA in situ hybridization revealed that two mutually exclusive last DAL19 exons were expressed in a cell-specific pattern within bud meristems. Based on these findings in DAL19, we developed a sensitive approach to transcript isoform assembly from short-read sequencing of mRNA. We applied this method to 42 putative MADS-box core regions in P abies, from which we assembled 1084 putative transcripts. We manually curated these transcripts to arrive at 933 assembled transcript isoforms of 38 putative MADS-box genes. 152 of these isoforms, which we assign to 28 putative MADS-box genes, were differentially expressed across eight female, male, and vegetative buds. We further provide evidence of the expression of 16 out of the 38 putative MADS-box genes by mapping PacBio Iso-Seq circular consensus reads derived from pooled sample sequencing to assembled transcripts. In summary, our analyses reveal the use of mutually exclusive exons of MADS-box gene isoforms during early bud development in P. abies, and we find that the large number of identified MADS-box transcripts in P. abies results not only from expansion of the gene family through gene duplication events but also from the generation of numerous splice variants.

  • 31.
    Akhter, Shirin
    et al.
    Sveriges Lantbruksuniversitet.
    Westrin, Karl Johan
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology.
    Zivi, Nathan
    Sveriges lantbruksuniversitet, Skogforsk.
    Nordal, Veronika
    Sveriges Lantbruksuniversitet.
    Kretzschmar, Warren W.
    Karolinska Institutet.
    Delhomme, Nicolas
    Sveriges Lantbruksuniversitet.
    Street, Nathaniel R.
    Umeå Universitet.
    Nilsson, Ove
    Sveriges Lantbruksuniversitet.
    Emanuelsson, Olof
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology.
    Sundström, Jens
    Sveriges lantbruksuniversitet.
    Transcriptome studies of the early cone-setting acrocona mutant provide evidence for a functional conservation of the age-dependent flowering pathway between angiosperms and gymnosperms.Manuscript (preprint) (Other academic)
    Abstract [en]

    All seed plants go through a juvenile period before they initiate seed- and pollen-bearing organs and reproduce. Reproductive phase-change is well characterized in angiosperm model species, but much less well described in gymnosperms. Here, we utilize the early cone-setting acrocona mutant to study reproductive phase change in the conifer Picea abies; a representative of the gymnosperm lineage. The acrocona mutant frequently initiates cone-like structures, called transition shoots, in positions where wild-type P. abies always produces vegetative shoots. By sequence analysis of mRNA and microRNA transcripts, we demonstrate that orthologous components of the Age-dependent flowering pathway are active at the time of cone initiation. We show that a member of the SQUAMOSA BINDING PROTEIN-LIKE (SPL) gene family, PaSPL7, is active in reproductive meristems, whereas a putative negative regulator of PaSPL7, microRNA156 is upregulated in vegetative meristem. By allele-specific assembly, we also identify a short nucleotide polymorphism (SNP) in the miRNA156 binding of PaSPL7. By genotyping a segregating population of inbred acrocona trees, we show a clear co-segregation between the early cone-setting phenotype and trees homozygous for the SNP. Hence, the data presented demonstrate evolutionary conservation of the age-dependent flowering pathway and involvement of this pathway in regulating cone-setting in the conifer P. abies.

  • 32.
    Akkuratov, Evgeny E.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biophysics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    The Biophysics of Na+,K+-ATPase in neuronal health and disease2020Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Na+,K+-ATPase is one of the most important proteins in the mammalian cell. It creates sodium and potassium gradients which are fundamental for the membrane potential and sodium-dependent secondary active transport. It has a second role in the cell as a receptor that by binding chemicals from the cardiotonic steroids family, the most knowledgeable of them is ouabain, triggers various signaling pathways in the cell which regulate gene activation, proliferation, apoptosis, etc. It has been shown that several severe neurological diseases are associated with mutations in the Na+,K+-ATPase encoding genes. Although Na+,K+-ATPase was discovered already in 1957 by the Danish scientist Jens Skou, the knowledge about the function of this enzyme  is still not complete.

     

    In the studies included in the thesis, we have learned more about the function of Na+,K+-ATPase in different aspects of health and disease. In study I we showed a mechanism of ouabain-dependent regulation of the NMDA receptor, one of the most important receptors in the nervous system, via binding with Na+,K+-ATPase. This allows us to look at the Na+,K+-ATPase as regulator via protein-protein interaction. In study II we investigated a different aspect of Na+,K+-ATPase functioning – to look at how binding of ouabain to Na+,K+-ATPase activates a number of signaling cascades by looking at the phosphoproteome status of the cells. This allows us to see the whole picture of ouabain-mediated cascades and further characterize them. In study III we focused on the role of Na+,K+-ATPase in severe epileptic encephalopathy caused by a mutation in the ATP1A1 gene. We performed a molecular and cellular study to describe how mutations affects protein structure and function and found that this mutation converts the ion pump to a nonspecific leak channel. In study IV we performed a translational study of the most common mutation for rapid-onset dystonia-parkinsonism. We studied how this mutation affects the nervous system on the protein-, cellular-, and organism level and found that the complete absence of ultraslow afterhyperpolarization (usAHP) could explain gait disturbances found in patients. In the on-going study we showed that Na+,K+-ATPase can oligomerize and that this effect is triggered by ouabain binding to the Na+,K+-ATPase. In this study, we utilized a novel fluorescence labelling approach and used biophysical techniques with single molecule sensitivity to track Na+,K+-ATPase interactions.

     

    In summary, we applied biophysical and molecular methods to study different aspects of the function of Na+,K+-ATPase, and gained insights that could be helpful not only for answering fundamental questions about Na+,K+-ATPase but also to find a treatment for patients with diseases associated with mutations in this protein.

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  • 33.
    Akkuratov, Evgeny E.
    et al.
    St Petersburg State Univ, Inst Translat Biomed, St Petersburg, Russia.
    Gelfand, Mikhail S.
    Skolkovo Inst Sci & Technol, Ctr Data Intens Biomed & Biotechnol, Moscow, Russia.;Russian Acad Sci, Inst Informat Transmiss Problems, Moscow, Russia.;Natl Res Univ, Higher Sch Econ, Fac Comp Sci, Moscow, Russia.;MM Lomonosov Moscow State Univ, Dept Bioengn & Bioinformat, Moscow, Russia..
    Khrameeva, Ekaterina E.
    Skolkovo Inst Sci & Technol, Ctr Data Intens Biomed & Biotechnol, Moscow, Russia.;Russian Acad Sci, Inst Informat Transmiss Problems, Moscow, Russia..
    Neanderthal and Denisovan ancestry in Papuans: A functional study2018In: Journal of Bioinformatics and Computational Biology, ISSN 0219-7200, E-ISSN 1757-6334, Vol. 16, no 2, article id 1840011Article in journal (Refereed)
    Abstract [en]

    Sequencing of complete nuclear genomes of Neanderthal and Denisovan stimulated studies about their relationship with modern humans demonstrating, in particular, that DNA alleles from both Neanderthal and Denisovan genomes are present in genomes of modern humans. The Papuan genome is a unique object because it contains both Neanderthal and Denisovan alleles. Here, we have shown that the Papuan genomes contain different gene functional groups inherited from each of the ancient people. The Papuan genomes demonstrate a relative prevalence of Neanderthal alleles in genes responsible for the regulation of transcription and neurogenesis. The enrichment of specific functional groups with Denisovan alleles is less pronounced; these groups are responsible for bone and tissue remodeling. This analysis shows that introgression of alleles from Neanderthals and Denisovans to Papuans occurred independently and retention of these alleles may carry specific adaptive advantages.

  • 34.
    Akkuratov, Evgeny E.
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biophysics.
    Sorrell, Frankie
    Souza, Vasco
    Paukar, Martin
    Picton, Laurence
    Jans, Daniel
    Andersson, Magnus
    Fritz, Nicolas
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biophysics.
    Zhang, Xiaoqun
    Liebmann, Thomas
    KTH.
    Lindskog, Maria
    KTH.
    Svenningsson, Per
    Miles, Gareth
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biophysics.
    Aperia, Anita
    KTH.
    Mechanisms by which the T613M mutation causes mobility and gait disturbances in Rapid-Onset Dystonia-ParkinsonismManuscript (preprint) (Other academic)
  • 35.
    Akkuratov, Evgeny E.
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biophysics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Westin, Linda
    Vazquez-Juarez, Erika
    de Marothy, Minttu
    Melnikova, Aleksandra K
    Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia, 119234.
    Blom, Hans
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biophysics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lindskog, Maria
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biophysics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Aperia, Anita
    Ouabain Modulates the Functional Interaction Between Na,K-ATPase and NMDA Receptor.2020In: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 57, no 10, p. 4018-4030Article in journal (Refereed)
    Abstract [en]

    The N-methyl-D-aspartate (NMDA) receptor plays an essential role in glutamatergic transmission and synaptic plasticity and researchers are seeking for different modulators of NMDA receptor function. One possible mechanism for its regulation could be through adjacent membrane proteins. NMDA receptors coprecipitate with Na,K-ATPase, indicating a potential interaction of these two proteins. Ouabain, a mammalian cardiotonic steroid that specifically binds to Na,K-ATPase and affects its conformation, can protect from some toxic effects of NMDA receptor activation. Here we have examined whether NMDA receptor activity and downstream effects can be modulated by physiological ouabain concentrations. The spatial colocalization between NMDA receptors and the Na,K-ATPase catalytic subunits on dendrites of cultured rat hippocampal neurons was analyzed with super-resolution dSTORM microscopy. The functional interaction was analyzed with calcium imaging of single hippocampal neurons exposed to 10 μM NMDA in presence and absence of ouabain and by determination of the ouabain effect on NMDA receptor-dependent long-term potentiation. We show that NMDA receptors and the Na,K-ATPase catalytic subunits alpha1 and alpha3 exist in same protein complex and that ouabain in nanomolar concentration consistently reduces the calcium response to NMDA. Downregulation of the NMDA response is not associated with internalization of the receptor or with alterations in its state of Src phosphorylation. Ouabain in nanomolar concentration elicits a long-term potentiation response. Our findings suggest that ouabain binding to a fraction of Na,K-ATPase molecules that cluster with the NMDA receptors will, via a conformational effect on the NMDA receptors, cause moderate but consistent reduction of NMDA receptor response at synaptic activation.

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  • 36.
    Akpe, Victor
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Photophysical and Chemical Approaches to Cellular Biophysics2008Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    The central theme in this thesis is reversibility. Two main attempts has been made to approach reversibility in cellular systems from both chemical and physical points of view. Reversibility of immunolabeling of proteins on the cell surface has been adressed by development of new fluorescent substances optimized for CALI (Chromophore-Assisted Laser Inactivation of protein). Aluminum phthalocyanine (AlPc) is here identified to be a good candidate for a new generation of fluorophores for efficient hydroxyl radical generation. It is shown that cells can be reversibly labeled with antibody-AlPc conjugates. In experiments on living cells the AlPcs were not only active as classic fluorophores but also as photocatalytic substances with destaining properties. Reversibility of cell immobilization is also reported, where cells cultured in microstructures were immobilized and 3D supported using hydrogels. Hydrogel formulation and application was optimized to achieve a system where both viability and ease of use was satisfied. Gel reversibility was actualized with pH and enzyme treatment. The developped method offers the possibility of stop flow culturing cells in controlled and reusable 3D environments.

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  • 37.
    Akpe, Victor
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Nyokong, Tebello
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Photophysics and photochemistry of zinc, aluminium and tin octakis (benzylthio) phthalocyanines2008Report (Other academic)
  • 38.
    Akpe, Victor
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Vernet, Erik
    KTH, School of Biotechnology (BIO), Molecular Biotechnology.
    Gräslund, Torbjörn
    KTH, School of Biotechnology (BIO), Molecular Biotechnology.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Characterization studies of aluminum phthalocyanine binding to antibodies from SKBR 3 cell line2008Report (Other academic)
  • 39.
    Aktay, Serhat
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology.
    Computational Pipeline for Analyses of Genome-Wide Nascent Transcription from PRO-seq Data2023Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Cells utilise various stress responses that are rapidly activated to avoid cell death under adverse conditions. Tracking gene transcription offers insight into the immediate changes in the cell, and one method to study the process of nascent transcription is precision run-on sequencing (PRO-seq). In PRO-seq, biotin-labeled nucleotides are added to halt the transcription as the RNA polymerase cannot continue transcription after incorporating biotin-labeled nucleotide to the nascent RNA. The biotin-labeled nascent RNAs are then isolated from the myriad of RNAs in the cell and sequenced. Simplifying the analysis of sequenced data and making the analysis more available for a larger group of scientist is needed, and therefore the aim of this thesis is to build a computational pipeline to analyse PRO-seq data. The pipeline consists of five shell and three R scripts that create a reference genome index for alignment, load experimental data, align the data to the reference genome, and output .bed and .bigWig files for further analysis. Using the profile of nascent transcription, the pipeline then identifies functional genomic regions and outputs gene expression activity based on engaged polymerase counts. The data used in this study are from heat shock cells from Homo sapiens, Canis lupis familiaris, Mus musculus, and Drosophila melanogaster. This analysis strategy provides a method to visualise gene lengths, map functional genomic regions, count engaged RNA polymerase and identify unannotated genes and enhancers. The analysis showed that the use of bidirectional transcription to study cell stress is more useful in mammals than in insects and that genes encoding chaperone machineries were induced in all organisms upon heat shock. The pipeline developed in this Masters Thesis offers a standardised and user-friendly method to study PRO-seq data and simplifies the analysis for laboratories with less experience in data analysis, additionally it is a tool to handle and automate processing of large amounts of data from distinct organisms. The computational pipeline outputs profiles of engaged RNA polymerases genome-wide, maps functional genomic regions, and counts transcriptional activity of genes and enhancers. 

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  • 40. Akyuz, Lalehan
    et al.
    Kaya, Murat
    Ilk, Sedef
    Cakmak, Yavuz Selim
    Salaberria, Asier M.
    Labidi, Jalel
    Yılmaz, Bahar Akyuz
    Sargin, Idris
    Effect of different animal fat and plant oil additives on physicochemical, mechanical, antimicrobial and antioxidant properties of chitosan films2018In: International Journal of Biological Macromolecules, ISSN 0141-8130, E-ISSN 1879-0003, Vol. 111, p. 475-484Article in journal (Refereed)
  • 41. Akyuz, Lalehan
    et al.
    Kaya, Murat
    Koc, Behlul
    Mujtaba, Muhammad
    Ilk, Sedef
    Labidi, Jalel
    Salaberria, Asier M.
    Cakmak, Yavuz Selim
    Yildiz, Aysegul
    Diatomite as a novel composite ingredient for chitosan film with enhanced physicochemical properties2017In: International Journal of Biological Macromolecules, ISSN 0141-8130, E-ISSN 1879-0003, Vol. 105, p. 1401-1411Article in journal (Refereed)
  • 42.
    Al Saleem, Evan
    KTH, School of Biotechnology (BIO).
    Improving unnatural amino acid mutagensis efficiency and selectivity in mammalian cell2016Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Genetically encoded, site-specific incorporation of unnatural amino acids (UAA)into proteins through selective recoding of an amber stop codon provides apowerful route for expressing synthetic proteins in living cells. Recoding of theamber stop codon is achieved by introducing an amber suppressortRNA/synthetase pair orthogonal to the endogenous tRNA complement intocells. Methanosarcina is a methane producing archaea with the unusualcapability of suppressing the stop codon (specifically the amber codon). Bysuppressing the amber codon Methanosarcina facilitate the incorporation of thenon-canonical amino acid pyrrolysine (pyl). The suppressing mechanismoriginates from a evolutionary unique Pyrrolysyl-tRNA synthetase (PylRS) and itsmatching tRNApyl. The PylRS has been further evolved and modified to allowincorporation of a wide range of UAAs. Amber suppression is today used tocontrol and study protein function in living cells. By making a series of wellcontrolledexperiments with HEK293T cells we aimed to develop this techniqueinto a robust and general tool for mammalian cell biology. Specifically we weretesting the incorporation of the unnatural amino acid bicyclononyne (BCN) by aset of known PylRS mutants. Our results suggest the mutant aaRS PylRS “AF” isthe most robust and efficient synthetase for BCN. We have improved ambersuppression by determining which factors leads to a more efficient method andsimultaneously decreasing the cost of the method.

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  • 43. Alava, Mikko
    et al.
    Ardelius, John
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Aurell, Erik
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Kaski, P.
    Krishnamurthy, S.
    Orponen, P.
    Seitz, S
    Circumspect descent prevails in solving random constraint satisfaction problems2008In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 105, no 40, p. 15253-15257Article in journal (Refereed)
    Abstract [en]

    We study the performance of stochastic local search algorithms for random instances of the K-satisfiability (K-SAT) problem. We present a stochastic local search algorithm, ChainSAT, which moves in the energy landscape of a problem instance by never going upwards in energy. ChainSAT is a focused algorithm in the sense that it focuses on variables occurring in unsatisfied clauses. We show by extensive numerical investigations that ChainSAT and other focused algorithms solve large K-SAT instances almost surely in linear time, up to high clause-to-variable ratios a; for example, for K = 4 we observe linear-time performance well beyond the recently postulated clustering and condensation transitions in the solution space. The performance of ChainSAT is a surprise given that by design the algorithm gets trapped into the first local energy minimum it encounters, yet no such minima are encountered. We also study the geometry of the solution space as accessed by stochastic local search algorithms.

  • 44.
    Albers, Eva
    et al.
    Chalmers Univ Technol, Dept Biol & Biol Engn, Div Ind Biotechnol, SE-41296 Gothenburg, Sweden..
    Malmhall-Bah, Eric
    Chalmers Univ Technol, Dept Biol & Biol Engn, Div Ind Biotechnol, SE-41296 Gothenburg, Sweden..
    Olsson, Joakim
    Chalmers Univ Technol, Dept Biol & Biol Engn, Div Ind Biotechnol, SE-41296 Gothenburg, Sweden..
    Sterner, Martin
    KTH, School of Architecture and the Built Environment (ABE), Sustainable development, Environmental science and Engineering, Water and Environmental Engineering.
    Mayers, Joshua J.
    Chalmers Univ Technol, Dept Biol & Biol Engn, Div Ind Biotechnol, SE-41296 Gothenburg, Sweden..
    Nylund, Goran M.
    Univ Gothenburg, Dept Marine Sci Tjarno, SE-45296 Stromstad, Sweden..
    Rupar-Gadd, Katarina
    Linnaeus Univ, Dept Built Environm & Energy Technol, Luckligs Plats 3, SE-35195 Växjö, Sweden..
    Abdollahi, Mehdi
    Chalmers Univ Technol, Dept Biol & Biol Engn, Div Food & Nutr Sci, SE-41296 Gothenburg, Sweden..
    Cvijetinovic, Suzana
    Chalmers Univ Technol, Dept Biol & Biol Engn, Div Ind Biotechnol, SE-41296 Gothenburg, Sweden..
    Welander, Ulrika
    Linnaeus Univ, Dept Built Environm & Energy Technol, Luckligs Plats 3, SE-35195 Växjö, Sweden..
    Edlund, Ulrica
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology.
    Pavia, Henrik
    Univ Gothenburg, Dept Marine Sci Tjarno, SE-45296 Stromstad, Sweden..
    Undeland, Ingrid
    Chalmers Univ Technol, Dept Biol & Biol Engn, Div Food & Nutr Sci, SE-41296 Gothenburg, Sweden..
    Influence of preservation methods on biochemical composition and downstream processing of cultivated Saccharina latissima biomass2021In: Algal Research, ISSN 2211-9264, Vol. 55, article id 102261Article in journal (Refereed)
    Abstract [en]

    Saccharina latissima biomass cultivated along the Swedish west coast was subjected to four different scalable preservation methods after harvest; freezing, sun-drying, oven-drying and ensiling. Freeze-drying and freezing at -80 ?C were also included to provide dry and wet references. The effects of the different preservation methods on the composition of Saccharina biomass (on dry weight, DW, basis), and the recovery as well as properties of high-quality protein, alginate and biogas were evaluated. Sun-drying significantly reduced protein, alginate and fatty acid content of the seaweeds and thereby concentrated ash in the biomass compared to the other methods. Protein/amino acids and fatty acids were significantly concentrated in ensiled biomass, while mannitol and laminarin were reduced compared to the other biomasses. Oven-drying and -20 ?C freezing affected the composition the least, with lower ash content and alterations in some specific amino and fatty acids. Sun-drying and ensiling resulted in significantly lower protein solubility at high pH compared to the other biomasses which translated into the lowest total seaweed protein recovery using the pH-shift process. Highest protein yield was obtained with the freeze-dried reference. Ensiling lead to a significant decrease in the molecular weight of alginate, while sun-drying caused a negative effect on alginate by inducing a shift in the guluronic and mannuronic acids composition of alginate. Sun-drying gave the lowest methane yield in the anaerobic digestion experiments while freezing at -80 ?C gave the highest yield, closely followed by freezing at -20 ?C and ensiling. To conclude, preservation methods must be carefully chosen to protect the valuable component in Saccharina latissima, and to achieve an efficient downstream processing ultimately yielding high quality products as part of a seaweed biorefinery.

  • 45.
    Albertsson, Ann-Christine
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology.
    Edlund, Ulrica
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology.
    Wood hydrolysates: From fractions to products2015In: Abstracts of Papers of the American Chemical Society, ISSN 0065-7727, Vol. 249Article in journal (Other academic)
  • 46.
    Albertsson, Ann-Christine
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology.
    Voepel, Jens
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology.
    Edlund, Ulrica
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology.
    Dahlman, Olof
    Soderqvist-Lindblad, Margaretha
    Design of Renewable Hydrogel Release Systems from Fiberboard Mill Wastewater2010In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 11, no 5, p. 1406-1411Article in journal (Refereed)
    Abstract [en]

    A new route for the design of renewable hydrogels is presented. The soluble waste from masonite production was isolated, fractionized, and upgraded. The resulting hemicellulose rich fraction was alkenyl-functionalized and used in the preparation of covalently cross-linked hydrogels capable of sustained release of incorporated agents. Said hydrogels showed a Fickian diffusion-based release of incorporated bovine serum albumin. Also, a method for the coating of seeds with hydrogel was developed. The sustained release of incorporated growth retardant agents from the hydrogel coating on rape seeds was shown to enable the temporary inhibition of germination.

  • 47.
    Alexeyenko, Andrey
    et al.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lee, Woojoo
    Pernemalm, Maria
    Guegan, Justin
    Dessen, Philippe
    Lazar, Vladimir
    Lehtio, Janne
    Pawitan, Yudi
    Network enrichment analysis: extension of gene-set enrichment analysis to gene networks2012In: BMC Bioinformatics, E-ISSN 1471-2105, Vol. 13, p. 226-Article in journal (Refereed)
    Abstract [en]

    Background: Gene-set enrichment analyses (GEA or GSEA) are commonly used for biological characterization of an experimental gene-set. This is done by finding known functional categories, such as pathways or Gene Ontology terms, that are over-represented in the experimental set; the assessment is based on an overlap statistic. Rich biological information in terms of gene interaction network is now widely available, but this topological information is not used by GEA, so there is a need for methods that exploit this type of information in high-throughput data analysis. Results: We developed a method of network enrichment analysis (NEA) that extends the overlap statistic in GEA to network links between genes in the experimental set and those in the functional categories. For the crucial step in statistical inference, we developed a fast network randomization algorithm in order to obtain the distribution of any network statistic under the null hypothesis of no association between an experimental gene-set and a functional category. We illustrate the NEA method using gene and protein expression data from a lung cancer study. Conclusions: The results indicate that the NEA method is more powerful than the traditional GEA, primarily because the relationships between gene sets were more strongly captured by network connectivity rather than by simple overlaps.

  • 48.
    Alexeyenko, Andrey
    et al.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Nystedt, Björn
    Vezzi, Francesco
    Sherwood, Ellen
    Ye, Rosa
    Knudsen, Bjarne
    Simonsen, Martin
    Turner, Benjamin
    de Jong, Pieter
    Wu, Cheng-Cang
    Lundeberg, Joakim
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Efficient de novo assembly of large and complex genomes by massively parallel sequencing of Fosmid pools2014In: BMC Genomics, E-ISSN 1471-2164, Vol. 15, no 1, p. 439-Article in journal (Refereed)
    Abstract [en]

    Background: Sampling genomes with Fosmid vectors and sequencing of pooled Fosmid libraries on the Illumina platform for massive parallel sequencing is a novel and promising approach to optimizing the trade-off between sequencing costs and assembly quality. Results: In order to sequence the genome of Norway spruce, which is of great size and complexity, we developed and applied a new technology based on the massive production, sequencing, and assembly of Fosmid pools (FP). The spruce chromosomes were sampled with similar to 40,000 bp Fosmid inserts to obtain around two-fold genome coverage, in parallel with traditional whole genome shotgun sequencing (WGS) of haploid and diploid genomes. Compared to the WGS results, the contiguity and quality of the FP assemblies were high, and they allowed us to fill WGS gaps resulting from repeats, low coverage, and allelic differences. The FP contig sets were further merged with WGS data using a novel software package GAM-NGS. Conclusions: By exploiting FP technology, the first published assembly of a conifer genome was sequenced entirely with massively parallel sequencing. Here we provide a comprehensive report on the different features of the approach and the optimization of the process. We have made public the input data (FASTQ format) for the set of pools used in this study: ftp://congenie.org/congenie/Nystedt_2013/Assembly/ProcessedData/FosmidPools/.(alternatively accessible via http://congenie.org/downloads).The software used for running the assembly process is available at http://research.scilifelab.se/andrej_alexeyenko/downloads/fpools/.

  • 49.
    Alexeyenko, Andrey
    et al.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Schmitt, Thomas
    Tjärnberg, Andreas
    Stockholm University, Science for Life Laboratory.
    Guala, Dmitri
    Stockholm University, Science for Life Laboratory.
    Frings, Oliver
    Stockholm University, Science for Life Laboratory.
    Sonnhammer, Erik L. L.
    Stockholm University, Science for Life Laboratory.
    Comparative interactomics with Funcoup 2.02012In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 40, no D1, p. D821-D828Article in journal (Refereed)
    Abstract [en]

    FunCoup (http://FunCoup.sbc.su.se) is a database that maintains and visualizes global gene/protein networks of functional coupling that have been constructed by Bayesian integration of diverse high-throughput data. FunCoup achieves high coverage by orthology-based integration of data sources from different model organisms and from different platforms. We here present release 2.0 in which the data sources have been updated and the methodology has been refined. It contains a new data type Genetic Interaction, and three new species: chicken, dog and zebra fish. As FunCoup extensively transfers functional coupling information between species, the new input datasets have considerably improved both coverage and quality of the networks. The number of high-confidence network links has increased dramatically. For instance, the human network has more than eight times as many links above confidence 0.5 as the previous release. FunCoup provides facilities for analysing the conservation of subnetworks in multiple species. We here explain how to do comparative interactomics on the FunCoup website.

  • 50.
    Alhamar, Sarah
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Extraction of the Coagulant Protein from Oil Waste2022Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Human health relies on clean water, and yet many developing countries have areas of poor water quality. This is either due to a lack of infrastructure and poor sanitation, or financial restrictions. One of the first steps of water treatment involves a process called flocculation. 

    Currently, aluminum sulfate (alum) is the most popular flocculation agent, but it has significant health implications. In contrast, the Moringa oleifera seed is a nonchemical additive which has historically been used in water treatment as a flocculation agent in addition to other applications in the cosmetic and food industries. 

    While Moringa oleifera seeds are one of the original plants used in water treatment, many others also show potential. The waste product from cold press oil industries was analyzed to test its viability as an alternative flocculation agent and to avoid competition with human consumption and industrial processes. Different oil wastes were screened to find a suitable coagulation agent. 

    Ion exchange chromatography and antimicrobial tests were conducted using simple assays. The screening was focused on the protein concentration and the coagulation activity of the oil cake presses. Moringa oleifera, rapeseed, linseed, peanut, and sesame seed oil press cakes were tested, of which two showed promising results and potential for use in water treatment. 

    The oil cake presses of Moringa seed and rapeseed showed the presence of coagulant proteins which are comparable to the seed extracts. The coagulant protein from the oil cake press has a similar molecular mass to that of seed extracts. The purified proteins displayed antibacterial properties, and their nutrient outputs were minimal. 

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  • asciidoc
  • rtf