| 1. |
- Reinthaler, Eva M., et al.
(författare)
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TPP2 mutation associated with sterile brain inflammation mimicking MS
- 2018
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Ingår i: NEUROLOGY-GENETICS. - 2376-7839. ; 4:6
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Tidskriftsartikel (refereegranskat)abstract
- Objective To ascertain the genetic cause of a consanguineous family from Syria suffering from a sterile brain inflammation mimicking a mild nonprogressive form of MS.Methods We used homozygosity mapping and next-generation sequencing to detect the disease-causing gene in the affected siblings. In addition, we performed RNA and protein expression studies, enzymatic activity assays, immunohistochemistry, and targeted sequencing of further MS cases from Austria, Germany, Canada and Jordan.Results In this study, we describe the identification of a homozygous missense mutation (c.82T>G, p.Cys28Gly) in the tripeptidyl peptidase II (TPP2) gene in all 3 affected siblings of the family. Sequencing of all TPP2-coding exons in 826 MS cases identified one further homozygous missense variant (c.2027C>T, p.Thr676Ile) in a Jordanian MS patient. TPP2 protein expression in whole blood was reduced in the affected siblings. In contrast, TPP2 protein expression in postmortem brain tissue from MS patients without TPP2 mutations was highly upregulated.Conclusions The homozygous TPP2 mutation (p.Cys28Gly) is likely responsible for the inflammation phenotype in this family. TPP2 is an ubiquitously expressed serine peptidase that removes tripeptides from the N-terminal end of longer peptides. TPP2 is involved in various biological processes including the destruction of major histocompatibility complex Class I epitopes. Recessive loss-of-function mutations in TPP2 were described in patients with Evans syndrome, a rare autoimmune disease affecting the hematopoietic system. Based on the gene expression results in our MS autopsy brain samples, we further suggest that TPP2 may play a broader role in the inflammatory process in MS.
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| 2. |
- Abbasi, Rasha, et al.
(författare)
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IceCube search for neutrinos from GRB 221009A
- 2023
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Ingår i: Proceedings of 38th International Cosmic Ray Conference (ICRC 2023). - : Sissa Medialab Srl.
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Konferensbidrag (refereegranskat)abstract
- GRB 221009A is the brightest Gamma Ray Burst (GRB) ever observed. The observed extremelyhigh flux of high and very-high-energy photons provide a unique opportunity to probe the predictedneutrino counterpart to the electromagnetic emission. We have used a variety of methods to searchfor neutrinos in coincidence with the GRB over several time windows during the precursor, promptand afterglow phases of the GRB. MeV scale neutrinos are studied using photo-multiplier ratescalers which are normally used to search for galactic core-collapse supernovae neutrinos. GeVneutrinos are searched starting with DeepCore triggers. These events don’t have directionallocalization, but instead can indicate an excess in the rate of events. 10 GeV - 1 TeV and >TeVneutrinos are searched using traditional neutrino point source methods which take into accountthe direction and time of events with DeepCore and the entire IceCube detector respectively. The>TeV results include both a fast-response analysis conducted by IceCube in real-time with timewindows of T0 − 1 to T0 + 2 hours and T0 ± 1 day around the time of GRB 221009A, as well asan offline analysis with 3 new time windows up to a time window of T0 − 1 to T0 + 14 days, thelongest time period we consider. The combination of observations by IceCube covers 9 ordersof magnitude in neutrino energy, from MeV to PeV, placing upper limits across the range forpredicted neutrino emission.
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| 3. |
- Agmo Hernández, Víctor, et al.
(författare)
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Electrochemistry of Adhesion and Spreading of Lipid Vesicles on Electrodes
- 2013
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Ingår i: Applications of Electrochemistry in Medicine. - Boston, MA : Springer US. - 9781461461487 ; , s. 189-247
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Biological membranes have developed to separate different compartments of organisms and cells. There is a large number of rather different functions which membranes have to fulfil: (1) they control the material and energy fluxes of metabolic processes, (2) they provide a wrapping protecting the compartments from chemical and physical attacks of the environment, (3) they provide interfaces at which specific biochemical machineries can operate (e.g., membrane bound enzymes), (4) they are equipped for signal transduction, (5) they possess the necessary stability and flexibility to allow cell division, and endo- and exocytosis as well as migration, (6) they present anchoring structures that enable cell-to-cell and cell-to-matrix physical interactions and intercellular communication. These are certainly not all functions of membranes as new functionalities are continuously reported. Since the biological membranes separate essentially aqueous solutions, such separating borders—if they should possess a reasonable stability and also flexibility combined with selective permeability—have to be built up of hydrophobic molecules exposing to both sides a similar interface. It was one of the most crucial and most lucky circumstances for the development and existence of life that certain amphiphilic molecules are able to assemble in bilayer structures (membranes), which—on one side—possess a rather high physical and chemical stability, and—on the other side—are able to incorporate foreign molecules for modifying both the physical properties as well as the permeability of the membranes for defined chemical species. The importance of the chemical function of membranes and all its constituents, e.g., ion channels, pore peptides, transport peptides, etc., is generally accepted. The fluid-mosaic model proposed by Singer and Nicolson [1] is still the basis to understand the biological, chemical, and physical properties of biological membranes. The importance of the purely mechanical properties of membranes came much later into the focus of research. The reasons are probably the dominance of biochemical thinking and biochemical models among biologists and medical researchers, as well as a certain lack of appropriate methods to probe mechanical properties of membranes. The last decades have changed that situation due to the development of techniques like the Atomic Force Microscopy, Fluorescence Microscopy, Micropipette Aspiration, Raman Microspectroscopy, advanced Calorimetry, etc. This chapter is aimed at elucidating how the properties of membranes can be investigated by studying the interaction of vesicles with a very hydrophobic surface, i.e., with the surface of a mercury electrode. This interaction is unique as it results in a complete disintegration of the bilayer membrane of the vesicles and the formation of an island of adsorbed lipid molecules, i.e., a monolayer island. This process can be followed by current-time measurements (chronoamperometry), which allow studying the complete disintegration process in all its details: the different steps of that disintegration can be resolved on the time scale and the activation parameters can be determined. Most interestingly, the kinetics of vesicle disintegration on mercury share important features with the process of vesicle fusion and, thus, sheds light also on mechanisms of endocytosis and exocytosis. Most importantly, not only artificial vesicles (liposomes) can be studied with this approach, but also reconstituted plasma membrane vesicles and even intact mitochondria. Hence, one can expect that the method may provide in future studies also information on the membrane properties of various other vesicles, including exosomes, and may allow investigating various aspects of drug action in relation to membrane properties (transmembrane transport, tissue targeting, bioavailability, etc.), and also the impact of pathophysiological conditions (e.g., oxidative modification) on membrane properties, on a hitherto not or only hardly accessible level.
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| 4. |
- Almqvist, Gustaf, et al.
(författare)
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Report of the Benchmark Workshop on Baltic Cod Stocks (WKBALTCOD)
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The ICES Benchmark Workshop on Baltic Cod Stocks (WKBALTCOD), chaired by External Chair Jean-Jacques Maguire, Canada and ICES Chair Marie Storr-Paulsen, Denmark, and attended by two invited external experts Verena Trenkel, France and Meaghan Bryan, USA met in Rostock, Germany, 2–6 March 2015 with 39 participants and six countries represented. The objective of WKBALTCOD was to evaluate the appropriateness of data and methods to determine stock status and investigate meth-ods appropriate to use in the single-stock assessment for the cod stock in SD 22–24 and cod in SD 25–32 in the Baltic. Participants in the workshop were a large group with diverse backgrounds representing the industry, fisheries, NGOs, managers and scientists.The single-stock analytic assessment of the eastern Baltic stock was not accepted by the assessment working group (WGBFAS) in 2014 due to severe problems with the input data. The advice for the eastern Baltic cod was, therefore, based on the ICES approach for data-limited stocks. As an outcome ICES decided to establish a bench-mark for both cod stocks and to scope an integrated assessment for the Baltic cod stocks. The first meeting (WKSIBCA) was therefore meant to introduce the interces-sional work conducted since the assessment working group in April 2014, and to reach some conclusions on how to proceed both in the short term (Benchmark in March 2015) and longer term (2–3 years) and was seen as a data compilation work-shop, there is produced a separate report from this workshop. The WKBALTCOD was the 2nd meeting in the benchmark process and was intended to come up with a final stock assessment method, stock annex and input data for both stocks. As it was not possible to reach conclusive decision on the final model to be used for the east Baltic cod stock during the benchmark meeting and as more work on the preferable models was needed, it was decided by the ACOM leadership to prolong the bench-mark process until the assessment working group meeting in April 2015. This deci-sion has led to a relatively long process partly mixed with the assessment working group WGBFAS.It became clear during the benchmark process that although large effort has been put into explaining the underlying processes leading to the changes in the Baltic ecosys-tem, there is still some lack of understanding of the present situation in the eastern Baltic cod stock. Therefore, it was not possible to reach firm conclusions on the final model to be used and therefore not possible to set reference points. It was decided to continue to explore the most promising models and to continue to improve the input data until the assessment working group started in April.The main challenges still to be solved for the Eastern Baltic cod stock is the quantifi-cation of increased natural mortality and decrease in growth. Through several presentations during the workshop (both WKSIBCA and WKBALTCOD) it became clear that natural mortality very likely has increased in later years, due to decreased condition and increased parasite infection. A decrease in growth also seems plausible duo to a decrease in condition and/or selectivity-induced mortality of the largest in-dividuals. However, as none of these parameters are easily estimated, especially with the severe ageing problems, different model assumptions made the output very shaky.For the western Baltic cod, stock identification issues were examined in area SD 24, the intermediate area: based on otolith characteristics and genetics. Due to the results showing a large proportion of east cod in this area, it was decided to split the catch2 | ICES WKBALTCOD REPORT 2015and survey from SD 24 into either the western or eastern Baltic cod stock. It was pos-sible to derive proportions of eastern and western cod in SD 24 back to the mid-1990s.For the western Baltic cod stock a modelled survey indices was included in the as-sessment covering the western part of SD 24 and Area 22+23 and based on a smoothed ALK.Both cod stocks have in the past used commercial tuning fleet to have a better cov-ered of older age groups. It was decided to abound this time-series duo quality issues such as a limited coverage and problems with technical creeping.WKBALTCOD was not able to explore and define reference points for the Western Baltic cod stock during the meeting due to time constraints, but these were calculated and decided by correspondence after the meeting. The recent protocols on estimation procedures developed by WKMSYREF3 for stocks with a full analytical assessment and for data-limited stocks served as objective guidelines to obtain reference point estimates.
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| 5. |
- Austeng, Dordi, et al.
(författare)
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Incidence of and risk factors for neonatal morbidity after active perinatal care : extremely preterm infants study in Sweden (EXPRESS)
- 2010
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 99:7, s. 978-992
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The aim of this study was to determine the incidence of neonatal morbidity in extremely preterm infants and to identify associated risk factors. Methods: Population based study of infants born before 27 gestational weeks and admitted for neonatal intensive care in Sweden during 2004-2007. Results: Of 638 admitted infants, 141 died. Among these, life support was withdrawn in 55 infants because of anticipation of poor long-term outcome. Of 497 surviving infants, 10% developed severe intraventricular haemorrhage (IVH), 5.7% cystic periventricular leucomalacia (cPVL), 41% septicaemia and 5.8% necrotizing enterocolitis (NEC); 61% had patent ductus arteriosus (PDA) and 34% developed retinopathy of prematurity (ROP) stage >= 3. Eighty-five per cent needed mechanical ventilation and 25% developed severe bronchopulmonary dysplasia (BPD). Forty-seven per cent survived to one year of age without any severe IVH, cPVL, severe ROP, severe BPD or NEC. Tocolysis increased and prolonged mechanical ventilation decreased the chances of survival without these morbidities. Maternal smoking and higher gestational duration were associated with lower risk of severe ROP, whereas PDA and poor growth increased this risk. Conclusion: Half of the infants surviving extremely preterm birth suffered from severe neonatal morbidities. Studies on how to reduce these morbidities and on the long-term health of survivors are warranted.
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| 6. |
- Fellman, Vineta, et al.
(författare)
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One-year survival of extremely preterm infants after active perinatal care in Sweden.
- 2009
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Ingår i: JAMA : the journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 301:21, s. 2225-33
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Tidskriftsartikel (refereegranskat)abstract
- Up-to-date information on infant survival after extremely preterm birth is needed for assessing perinatal care services, clinical guidelines, and parental counseling.
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| 7. |
- Feyerabend, Moritz, et al.
(författare)
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Hybrid simulation of Titan's interaction with the supersonic solar wind during Cassini's T96 flyby
- 2016
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 43:1, s. 35-42
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Tidskriftsartikel (refereegranskat)abstract
- By applying a hybrid (kinetic ions and fluid electrons) simulation code, we study the plasma environment of Saturn's largest moon Titan during Cassini's T96 flyby on 1 December 2013. The T96 encounter marks the only observed event of the entire Cassini mission where Titan was located in the supersonic solar wind in front of Saturn's bow shock. Our simulations can quantitatively reproduce the key features of Cassini magnetic field and electron density observations during this encounter. We demonstrate that the large-scale features of Titan's induced magnetosphere during T96 can be described in terms of a steady state interaction with a high-pressure solar wind flow. About 40min before the encounter, Cassini observed a rotation of the incident solar wind magnetic field by almost 90 degrees. We provide strong evidence that this rotation left a bundle of fossilized magnetic field lines in Titan's ionosphere that was subsequently detected by the spacecraft.
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| 8. |
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| 9. |
- Sommer, Robert S., et al.
(författare)
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Holocene recolonization and extinction of the pond turtle, Emys orbicularis (L., 1758), in Europe
- 2007
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791. ; 26:25-28, s. 3099-3107
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Tidskriftsartikel (refereegranskat)abstract
- We reconstruct the Holocene range fluctuations of the European pond turtle (Emys orbicularis) for northern and Central Europe. Based on 529 subfossil records and radiocarbon dating of critical finds, we provide evidence that E. orbicularis experienced a rapid range expansion with Holocene warming. Phylogeographic data argue for a colonization of northern and Central Europe from a glacial refuge located in the south-eastern Balkans. Already in the Late Preboreal (9100-8600 cal BC) the species occurred in northern Central Europe and was widespread in Denmark and southern Sweden (Skane) during the Boreal (8600-7100 cal BC). The maximum range extension occurred during the Holocene climatic optimum (Atlantic: 7100-3750 cal BC), with records in southern England, middle Sweden, and northern Estonia. After the early Subboreal (3750-1750 cal BC) northern populations collapsed, coinciding with a climatic cooling and oceanization. Northern populations were most likely established via long distance dispersal (rafting using rivers debouching in the North and Baltic Seas); after northern Europe was reached, a minimum dispersal of 50 km per 100 years may be hypothesized for the Boreal. (c) 2007 Elsevier Ltd. All rights reserved.
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| 10. |
- Sommer, Robert S., et al.
(författare)
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Unexpected early extinction of the European pond turtle (Emys orbicularis) in Sweden and climatic impact on its Holocene range
- 2009
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Ingår i: Molecular Ecology. - 0962-1083. ; 18:6, s. 1252-1262
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Tidskriftsartikel (refereegranskat)abstract
- Using ancient DNA sequences of subfossil European pond turtles (Emys orbicularis) from Britain, Central and North Europe and accelerator mass spectrometry radiocarbon dating for turtle remains from most Swedish sites, we provide evidence for a Holocene range expansion of the pond turtle from the southeastern Balkans into Britain, Central Europe and Scandinavia, according to the 'grasshopper pattern' of Hewitt. Northeastern Europe and adjacent Asia were colonized from another refuge located further east. With increasing annual mean temperatures, pond turtles reached southern Sweden approximately 9800 years ago. Until approximately 5500 years ago, rising temperatures facilitated a further range expansion up to ostergotland, Sweden (approximately 58 degrees 30'N). However, around 5500 years ago pond turtle records suddenly terminate in Sweden, some 1500 years before the Holocene thermal maximum ended in Scandinavia and distinctly earlier than previously thought. This extinction coincides with a temporary cooling oscillation during the Holocene thermal maximum and is likely related to lower summer temperatures deteriorating reproductive success. Although climatic conditions improved later again, recolonization of Sweden from southern source populations was prevented by the Holocene submergence of the previous land connection via the Danish Straits that occurred approximately 8500 years ago.
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| 11. |
- Sommer, Robert S., et al.
(författare)
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When the pond turtle followed the reindeer: effect of the last extreme global warming event on the timing of faunal change in Northern Europe
- 2011
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013. ; 17:6, s. 2049-2053
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Tidskriftsartikel (refereegranskat)abstract
- Faunal communities have been shaped in different ways by past climatic change. The impact of the termination of the last Glacial and the onset of the present (Holocene) Interglacial on large-scale faunal shifts, extinction dynamics and gene pools of species are of special interest in natural sciences. A general pattern of climate-triggered range expansion and local extinction of vertebrate species is known for Europe, and shows that in the modern temperate zone the main faunal change took place mainly during the Late Glacial (14 700-11 700 years ago) and Early Holocene (11 700-9 100 years ago). Based on large datasets of new radiocarbon data, we present precise temporal dynamics of climate-driven disappearance and appearance of reindeer and pond turtle in southern Sweden. These two species are significant climate indicators in Late Quaternary biostratigraphy. Our data reveal that the reindeer disappeared from southern Sweden ca. 10 300 years ago, whereas the pond turtle colonized the area ca. 9 860 years ago, with a 450-year gap between each species. This provides evidence for a sudden environmental turnover, causing the replacement of an arctic faunal element by a thermophilic species. The postglacial range dynamics of pond turtle and reindeer are a unique model case, allowing insights into the faunal turnover of other vertebrates during the last dramatic natural global warming event at the Pleistocene-Holocene transition.
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| 12. |
- Suh, Alexander Sang-Jae, et al.
(författare)
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Early Mesozoic Coexistence of Amniotes and Hepadnaviridae
- 2014
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 10:12, s. e1004559-
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Tidskriftsartikel (refereegranskat)abstract
- Hepadnaviridae are double-stranded DNA viruses that infect some species of birds and mammals. This includes humans, where hepatitis B viruses (HBVs) are prevalent pathogens in considerable parts of the global population. Recently, endogenized sequences of HBVs (eHBVs) have been discovered in bird genomes where they constitute direct evidence for the coexistence of these viruses and their hosts from the late Mesozoic until present. Nevertheless, virtually nothing is known about the ancient host range of this virus family in other animals. Here we report the first eHBVs from crocodilian, snake, and turtle genomes, including a turtle eHBV that endogenized >207 million years ago. This genomic "fossil'' is >125 million years older than the oldest avian eHBV and provides the first direct evidence that Hepadnaviridae already existed during the Early Mesozoic. This implies that the Mesozoic fossil record of HBV infection spans three of the five major groups of land vertebrates, namely birds, crocodilians, and turtles. We show that the deep phylogenetic relationships of HBVs are largely congruent with the deep phylogeny of their amniote hosts, which suggests an ancient amniote-HBV coexistence and codivergence, at least since the Early Mesozoic. Notably, the organization of overlapping genes as well as the structure of elements involved in viral replication has remained highly conserved among HBVs along that time span, except for the presence of the X gene. We provide multiple lines of evidence that the tumor-promoting X protein of mammalian HBVs lacks a homolog in all other hepadnaviruses and propose a novel scenario for the emergence of X via segmental duplication and overprinting of pre-existing reading frames in the ancestor of mammalian HBVs. Our study reveals an unforeseen host range of prehistoric HBVs and provides novel insights into the genome evolution of hepadnaviruses throughout their long-lasting association with amniote hosts.
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