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Sökning: AMNE:(NATURAL SCIENCES Biological Sciences Biophysics)

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1.
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2.
  • Aurell, Erik, 1961-, et al. (författare)
  • The bulk and the tail of minimal absent words in genome sequences
  • 2016
  • Ingår i: Physical Biology. - : Institute of Physics (IOP). - 1478-3967 .- 1478-3975. ; 13:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Minimal absent words (MAW) of a genomic sequence are subsequences that are absent themselves but the subwords of which are all present in the sequence. The characteristic distribution of genomic MAWs as a function of their length has been observed to be qualitatively similar for all living organisms, the bulk being rather short, and only relatively few being long. It has been an open issue whether the reason behind this phenomenon is statistical or reflects a biological mechanism, and what biological information is contained in absent words. % In this work we demonstrate that the bulk can be described by a probabilistic model of sampling words from random sequences, while the tail of long MAWs is of biological origin. We introduce the novel concept of a core of a minimal absent word, which are sequences present in the genome and closest to a given MAW. We show that in bacteria and yeast the cores of the longest MAWs, which exist in two or more copies, are located in highly conserved regions the most prominent example being ribosomal RNAs (rRNAs). We also show that while the distribution of the cores of long MAWs is roughly uniform over these genomes on a coarse-grained level, on a more detailed level it is strongly enhanced in 3' untranslated regions (UTRs) and, to a lesser extent, also in 5' UTRs. This indicates that MAWs and associated MAW cores correspond to fine-tuned evolutionary relationships, and suggest that they can be more widely used as markers for genomic complexity.
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3.
  • Bertaccini, Edward J, et al. (författare)
  • Modeling anesthetic binding sites within the glycine alpha one receptor based on prokaryotic ion channel templates : the problem with TM4
  • 2010
  • Ingår i: Journal of chemical information and modeling. - 1549-9596 .- 1549-960X. ; 50:12, s. 2248-2255
  • Tidskriftsartikel (refereegranskat)abstract
    • Ligand-gated ion channels (LGICs) significantly modulate anesthetic effects. Their exact molecular structure remains unknown. This has led to ambiguity regarding the proper amino acid alignment within their 3D structure and, in turn, the location of any anesthetic binding sites. Current controversies suggest that such a site could be located in either an intra- or intersubunit locale within the transmembrane domain of the protein. Here, we built a model of the glycine alpha one receptor (GlyRa1) based on the open-state structures of two new high-resolution ion channel templates from the prokaryote, Gloebacter violaceus (GLIC). Sequence scoring suggests reasonable homology between GlyRa1 and GLIC. Three of the residues notable for modulating anesthetic action are on transmembrane segments 1-3 (TM1-3): (ILE229, SER 267, and ALA 288). They line an intersubunit interface, in contrast to previous models. However, residues from the fourth transmembrane domain (TM4) that are known to modulate a variety of anesthetic effects are quite distant from this putative anesthetic binding site. While this model can account for a large proportion of the physicochemical data regarding such proteins, it cannot readily account for the alterations on anesthetic effects that are due to mutations within TM4.
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4.
  • Unnerståle, Sofia (författare)
  • NMR Investigations of Peptide-Membrane Interactions, Modulation of Peptide-Lipid Interaction as a Switch in Signaling across the Lipid Bilayer
  • 2010
  • Licentiatavhandling (övrigt vetenskapligt)abstract
    • The complexity of multi cellular organisms demands systems that facilitate communicationbetween cells. The neurons in our brains for instance are specialized in this cell-cellcommunication. The flow of ions, through their different ion channels, across the membrane, isresponsible for almost all of the communication between neurons in the brain by changing theneurons membrane potentials. Voltage-gated ion channels open when a certain thresholdpotential is reached. This change in membrane potential is detected by voltage-sensors in the ionchannels. In this licentiate thesis the Homo sapiens voltage- and calcium-gated BK potassiumchannel (HsapBK) has been studied. The NMR solution structure of the voltage-sensor ofHsapBK was solved to shed light upon the voltage-gating in these channels. Structures of othervoltage-gated potassium channels (Kv) have been determined by other groups, enablingcomparison among different types of Kv channels. Interestingly, the peptide-lipid interactions ofthe voltage-sensor in HsapBK are crucial for its mechanism of action.Uni cellular organisms need to sense their environment too, to be able to move towardsmore favorable areas and from less favorable ones, and to adapt their gene profiles to currentcircumstances. This is accomplished by the two-component system, comprising a sensor proteinand a response regulator. The sensor protein transfers signals across the membrane to thecytoplasm. Many sensor proteins contain a HAMP domain close to the membrane that isinvolved in transmitting the signal. The mechanism of this transfer is not yet revealed. Ourstudies show that HAMP domains can be divided into two groups based on the membraneinteraction of their AS1 segments. Further, these two groups are suggested to work by differentmechanisms; one membrane-dependent and one membrane-independent mechanism.Both the voltage-gating mechanism and the signal transduction carried out by HAMPdomains in the membrane-dependent group, demand peptide-lipid interactions that can be readilymodulated. This modulation enables movement of peptides within membranes or within thelipid-water interface. These conditions make these peptides especially suitable for NMR studies.
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5.
  • Wojcik, Andrzej, et al. (författare)
  • Educating about radiation risks in high schools : towards improved public understanding of the complexity of low-dose radiation health effects
  • 2019
  • Ingår i: Radiation and Environmental Biophysics. - : SPRINGER. - 0301-634X .- 1432-2099. ; 58:1, s. 13-20
  • Tidskriftsartikel (refereegranskat)abstract
    • The levels of stochastic health effects following exposure to low doses of ionising radiation are not well known. A consequence of the uncertainty is that any radiation exposure is met with deep concernboth by the public and by scientists who disagree about how the partly conflicting results from low-dose studies should be interpreted. The concern is not limited to ionising radiation but is inherent to other areas of modern technologies such as biotechnology or electromagnetic fields. The everyday presence of advanced technologies confronts people with the necessity to take decisions and there is an ongoing debate regarding both the nature and magnitude of potential risks and how education efforts may empower peoples ' decision-making. In the field of radiation research there are different opinions regarding the optimal education methods, spanning from the idea that peoples' fears will be eliminated by introducing dose thresholds below which the risk is assumed to be zero, to suggestions of concentrating research efforts in an attempt to eliminate all uncertainties regarding the effects of low doses. The aim of this paper was to present our approach which is based on developing an education program at the secondary school level where students learn to understand the role of science in society. Teaching about radiation risk as a socio-scientific issue is not based on presenting facts but on showing risks in a broader perspective aiming at developing students' competency in making decisions based on informed assessment. We hope to stimulate and encourage other researchers to pursue similar approaches.
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6.
  • Aronsson, Christopher (författare)
  • Tunable and modular assembly of polypeptides and polypeptide-hybrid biomaterials
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Biomaterials are materials that are specifically designed to be in contact with biological systems and have for a long time been used in medicine. Examples of biomaterials range from sophisticated prostheses used for replacing outworn body parts to ordinary contact lenses. Currently it is possible to create biomaterials that can e.g. specifically interact with cells or respond to certain stimuli. Peptides, the shorter version of proteins, are excellent molecules for fabrication of such biomaterials. By following and developing design rules it is possible to obtain peptides that can self-assemble into well-defined nanostructures and biomaterials.The aim of this thesis is to create ”smart” and tunable biomaterials by molecular self-assembly using dimerizing –helical polypeptides. Two different, but structurally related, polypeptide-systems have been used in this thesis. The EKIV-polypeptide system was developed in this thesis and consists of four 28-residue polypeptides that can be mixed-and-matched to self-assemble into four different coiled coil heterodimers. The dissociation constant of the different heterodimers range from μM to < nM. Due to the large difference in affinities, the polypeptides are prone to thermodynamic social self-sorting. The JR-polypeptide system, on the other hand, consists of several 42-residue de novo designed helix-loop-helix polypeptides that can dimerize into four-helix bundles. In this work, primarily the glutamic acid-rich polypeptide JR2E has been explored as a component in supramolecular materials. Dimerization was induced by exposing the polypeptide to either Zn2+, acidic conditions or the complementary polypeptide JR2K.By conjugating JR2E to hyaluronic acid and the EKIV-polypeptides to star-shaped poly(ethylene glycol), respectively, highly tunable hydrogels that can be self-assembled in a modular fashion have been created. In addition, self-assembly of spherical superstructures has been investigated and were obtained by linking two thiol-modified JR2E polypeptides via a disulfide bridge in the loop region. ŒThe thesis also demonstrates that the polypeptides and the polypeptide-hybrids can be used for encapsulation and release of molecules and nanoparticles. In addition, some of the hydrogels have been explored for 3D cell culture. By using supramolecular interactions combined with bio-orthogonal covalent crosslinking reactions, hydrogels were obtained that enabled facile encapsulation of cells that retained high viability.The results of the work presented in this thesis show that dimerizing α–helical polypeptides can be used to create modular biomaterials with properties that can be tuned by specific molecular interactions. The modularity and the tunable properties of these smart biomaterials are conceptually very interesting andmake them useful in many emerging biomedical applications, such as 3D cell culture, cell therapy, and drug delivery.
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7.
  • Sandén, Tor, et al. (författare)
  • Surface-coupled proton exchange of a membrane-bound proton acceptor
  • 2010
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - Washington : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 107:9, s. 4129-4134
  • Tidskriftsartikel (refereegranskat)abstract
    • Proton-transfer reactions across and at the surface of biological membranes are central for maintaining the transmembrane proton electrochemical gradients involved in cellular energy conversion. In this study, fluorescence correlation spectroscopy was used to measure the local protonation and deprotonation rates of single pH-sensitive fluorophores conjugated to liposome membranes, and the dependence of these rates on lipid composition and ion concentration. Measurements of proton exchange rates over a wide proton concentration range, using two different pH-sensitive fluorophores with different pKas, revealed two distinct proton exchange regimes. At high pH (> 8), proton association increases rapidly with increasing proton concentrations, presumably because the whole membrane acts as a proton-collecting antenna for the fluorophore. In contrast, at low pH (< 7), the increase in the proton association rate is slower and comparable to that of direct protonation of the fluorophore from the bulk solution. In the latter case, the proton exchange rates of the two fluorophores are indistinguishable, indicating that their protonation rates are determined by the local membrane environment. Measurements on membranes of different surface charge and at different ion concentrations made it possible to determine surface potentials, as well as the distance between the surface and the fluorophore. The results from this study define the conditions under which biological membranes can act as proton-collecting antennae and provide fundamental information on the relation between the membrane surface charge density and the local proton exchange kinetics.
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8.
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9.
  • Freire, Rafael V.M., et al. (författare)
  • Antimicrobial peptide induced colloidal transformations in bacteria-mimetic vesicles : combining in silico tools and experimental methods
  • 2021
  • Ingår i: Journal of Colloid and Interface Science. - : Elsevier. - 0021-9797 .- 1095-7103. ; 596, s. 352-363
  • Tidskriftsartikel (refereegranskat)abstract
    • With the growing challenges of bacteria becoming resistant to conventional antibiotics, antimicrobial peptides (AMPs) may offer a potential alternative. One of the most studied AMPs, the human cathelicidin derived AMP LL-37 is notable for its antimicrobial activity even though its mechanism of action is not fully understood yet. This work investigates the interaction of LL-37 with 1-Palmitoyl-2-oleoyl-sn-glycero-3-phospho-rac-(1-glycerol) (POPG) vesicles, which were employed as a bacterial membrane model given the common presence of this phospholipid in the bacterial membrane. Experimental techniques including small angle X-ray scattering, transmission electron microscopy and dynamic light scattering were used to characterize the interactions among LL-37 and POPG. Molecular dynamics simulations complement the experimental studies with molecular-level insights into the process. LL-37 was discovered to actively and critically interact with the POPG vesicles, modifying the membrane curvature that eventually leads to structural transformations from vesicles to mixed micelles. The results shed light on the mechanisms underlying the interactions among LL-37 and bacteria mimetic vesicles and can guide the further development of AMP based antimicrobial materials and therapies.
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10.
  • KjÊrvik, Marit, et al. (författare)
  • Comparative Study of NAP-XPS and Cryo-XPS for the Investigation of Surface Chemistry of the Bacterial Cell-Envelope
  • 2021
  • Ingår i: Frontiers in Chemistry. - : Frontiers Media S.A.. - 2296-2646. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Bacteria generally interact with the environment via processes involving their cell-envelope. Thus, techniques that may shed light on their surface chemistry are attractive tools for providing an understanding of bacterial interactions. One of these tools is Al Kα-excited photoelectron spectroscopy (XPS) with its estimated information depth of <10 nm. XPS-analyses of bacteria have been performed for several decades on freeze-dried specimens in order to be compatible with the vacuum in the analysis chamber of the spectrometer. A limitation of these studies has been that the freeze-drying method may collapse cell structure as well as introduce surface contaminants. However, recent developments in XPS allow for analysis of biological samples at near ambient pressure (NAP-XPS) or as frozen hydrated specimens (cryo-XPS) in vacuum. In this work, we have analyzed bacterial samples from a reference strain of the Gram-negative bacterium Pseudomonas fluorescens using both techniques. We compare the results obtained and, in general, observe good agreement between the two techniques. Furthermore, we discuss advantages and disadvantages with the two analysis approaches and the output data they provide. XPS reference data from the bacterial strain are provided, and we propose that planktonic cells of this strain (DSM 50090) are used as a reference material for surface chemical analysis of bacterial systems.
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