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  • 101. Gand, Georges
    et al.
    Tuysuz, Okan
    Steyer, J. Sebastien
    Allain, Ronan
    Sakinc, Mehmet
    Sanchez, Sophie
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Sengor, A. M. Celal
    Sen, Sevket
    New Permian tetrapod footprints and macroflora from Turkey (Cakraz Formation, northwestern Anatolia): Biostratigraphic and palaeoenvironmental implications2011Ingår i: Comptes rendus. Palevol, ISSN 1631-0683, E-ISSN 1777-571X, Vol. 10, nr 8, s. 617-625Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    New tetrapod footprints belonging to the ichnogenus Hyloidichnus have been discovered in Turkey for the first time, in the lower part of the Cakraz Formation (Northwestern Anatolia) and together with macrofloral imprints of Annularia and Stigmaria. These discoveries confirm the Permian age of the fossiliferous red beds in which the coniferophyte Walchia was previously recorded. Based on the stratigraphic range of Annularia,Stigmaria and Hyloidichnus known elsewhere, a Cisuralian age is proposed for these beds. These new ichno- and macrofloral remains, together with the sedimentological data (mudcracks, rain drops) suggest the presence of captorhinid reptiles living in a palustrine floodplain environment, and under a warm, seasonal climate alternating between humid and relatively long dry seasons. These climatic conditions may have permitted the migration of these captorhinids through Laurasia during the Permian.

  • 102.
    Gattepaille, Lucie
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Evolutionsbiologi.
    Günther, Torsten
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Jakobsson, Mattias
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Inferring Past Effective Population Size from Distributions of Coalescent Times2016Ingår i: Genetics, ISSN 0016-6731, E-ISSN 1943-2631, Vol. 204, nr 3, s. 1191-1206Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Inferring and understanding changes in effective population size over time is a major challenge for population genetics. Here we investigate some theoretical properties of random-mating populations with varying size over time. In particular, we present an exact solution to compute the population size as a function of time, N-e(t), based on distributions of coalescent times of samples of any size. This result reduces the problem of population size inference to a problem of estimating coalescent time distributions. To illustrate the analytic results, we design a heuristic method using a tree-inference algorithm and investigate simulated and empirical population-genetic data. We investigate the effects of a range of conditions associated with empirical data, for instance number of loci, sample size, mutation rate, and cryptic recombination. We show that our approach performs well with genomic data ( 10,000 loci) and that increasing the sample size from 2 to 10 greatly improves the inference of Ne(t) whereas further increase in sample size results in modest improvements, even under a scenario of exponential growth. We also investigate the impact of recombination and characterize the potential biases in inference of Ne(t). The approach can handle large sample sizes and the computations are fast. We apply our method to human genomes from four populations and reconstruct population size profiles that are coherent with previous finds, including the Out-of-Africa bottleneck. Additionally, we uncover a potential difference in population size between African and non-African populations as early as 400 KYA. In summary, we provide an analytic relationship between distributions of coalescent times and Ne(t), which can be incorporated into powerful approaches for inferring past population sizes from population-genomic data.

  • 103.
    Geissler, Jan
    et al.
    European Patients Acad Therapeut Innovat, Rothenanger 1b, D-85521 Riemerling, Germany..
    Ryll, Bettina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi. Melanoma Patient Network Europe, Uppsala, Sweden..
    di Priolo, Susanna Leto
    Novartis Oncol Reg Europe, Patient Strategy, Haematol & Profess Relat, Milan, Italy..
    Uhlenhopp, Mary
    Amgen Europe GmbH, Zug, Switzerland.;Shire, Global Advocacy, Oncol & Immunol, Zug, Switzerland..
    Improving Patient Involvement in Medicines Research and Development:: A Practical Roadmap2017Ingår i: Therapeutic Innovation and Regulatory Science, ISSN 2168-4790, E-ISSN 2168-4804, Vol. 51, nr 5, s. 612-619Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The value of patient involvement (PI) in medicines research and development (R&D) is increasingly recognized by all health stakeholders. Despite numerous ongoing PI initiatives, PI so far lacks structure and consistency in approach. Limited formal documentation of PI activities further hampers the sharing of experience and learnings, preventing timely and systematic implementation. This article summarizes the outcomes of several multistakeholder discussions during 2013-2016 in a practical roadmap for PI in medicines R&D. The roadmap highlights specific opportunities for PI along the 4 key stages of the medicines R&D life cycle and is illustrated with concrete examples. This roadmap's aim is to provide a tool to facilitate PI during medicines research and development and is being shared to encourage implementation and further refinement.

  • 104. Germain, Damien
    et al.
    Sanchez, Sophie
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Janvier, Philippe
    Tafforeau, Paul
    The presumed hagfish Myxineidus gononorum from the Upper Carboniferous of Montceau-les-Mines (Saone-et-Loire, France): New data obtained by means of Propagation Phase Contrast X-ray Synchrotron Microtomography2014Ingår i: Annales de Paléontologie, ISSN 0753-3969, E-ISSN 1778-3666, Vol. 100, nr 2, s. 131-135Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The re-examination of the presumed hagfish Myxineidus gononorum from the Carboniferous of Montceaules-Mines by means of propagation phase contrast X-ray synchrotron microtomography confirms the presence of two series of non-mineralized denticles arranged in chevrons in the oral region. It also indicates the presence of possible traces of post-mortem mineralized soft tissues. A peculiar zone of less X ray-absorbing matter around the animal suggests the presence of an enlarged, lamprey-like oral disc. Re-interpreting Myxineidus as a lamprey would be in better agreement with the reputedly fresh-water environment of the Montceau-les-Mines Lagerstatte. 

  • 105.
    Gess, Robert
    et al.
    Rhodes Univ, Albany Museum, Grahamstown, South Africa;Rhodes Univ, Geol Dept, Grahamstown, South Africa.
    Ahlberg, Per
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    A tetrapod fauna from within the Devonian Antarctic Circle2018Ingår i: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 360, nr 6393, s. 1120-1124Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Until now, all known fossils of tetrapods (limbed vertebrates with digits) and near-tetrapods (such as Elpistostege, Tiktaalik, and Panderichthys) from the Devonian period have come from localities in tropical to subtropical paleolatitudes. Most are from Laurussia, a continent incorporating Europe, Greenland, and North America, with only one body fossil and one footprint locality from Australia representing the southern supercontinent Gondwana. Here we describe two previously unknown tetrapods from the Late Devonian (late Famennian) Gondwana locality of Waterloo Farm in South Africa, then located within the Antarctic Circle, which demonstrate that Devonian tetrapods were not restricted to warm environments and suggest that they may have been global in distribution.

  • 106.
    Gierlinski, Gerard D.
    et al.
    Moab Giants, 112W-SR 313 Moab, Moab, UT 84532 USA;Polish Res Inst, Polish Geol Inst, Rakowiecka 4, PL-00975 Warsaw, Poland.
    Niedzwiedzki, Grzegorz
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Lockley, Martin G.
    Moab Giants, 112W-SR 313 Moab, Moab, UT 84532 USA;Univ Colorado Denver, Dinosaur Tracks Museum, POB 173364, Denver, CO 80217 USA.
    Athanassiou, Athanassios
    Ephorate Palaeoanthropol Speleol, Hellen Minist Culture & Sports, Ardittou 34B, GR-11636 Athens, Greece.
    Fassoulas, Charalampos
    Univ Crete, Nat Hist Museum, Iraklion 71409, Greece.
    Dubicka, Zofia
    Univ Warsaw, Fac Geol, Zwirki & Wiguty 93, PL-02089 Warsaw, Poland.
    Boczarowski, Andrzej
    Park Sci & Human Evolut, 1 Maja 10, PL-46040 Krasiejow, Poland;Moab Giants, 112W-SR 313 Moab, Moab, UT 84532 USA;Stowarzyszenie Delta Delta Assoc, Sandomierska 4, PL-27400 Ostrowiec Swietokrzyski, Poland;Univ Silesia, Fac Earth Sci, Bedzinska 60, PL-41200 Sosnowiec, Poland.
    Bennett, Matthew R.
    Bournemouth Univ, Inst Studies Landscapes & Human Evolut, Poole BH12 5BB, Dorset, England.
    Ahlberg, Per Erik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Possible hominin footprints from the late Miocene (c. 5.7 Ma) of Crete?2017Ingår i: Proceedings Geological Association, ISSN 0016-7878, Vol. 128, nr 5-6, s. 697-710Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We describe late Miocene tetrapod footprints (tracks) from the Trachilos locality in western Crete (Greece), which show hominin-like characteristics. They occur in an emergent horizon within an otherwise marginal marine succession of Messinian age (latest Miocene), dated to approximately 5.7 Ma (million years), just prior to the Messinian Salinity Crisis. The tracks indicate that the trackmaker lacked claws, and was bipedal, plantigrade, pentadactyl and strongly entaxonic. The impression of the large and non-divergent first digit (hallux) has a narrow neck and bulbous asymmetrical distal pad. The lateral digit impressions become progressively smaller so that the digital region as a whole is strongly asymmetrical. A large, rounded ball impression is associated with the hallux. Morphometric analysis shows the footprints to have outlines that are distinct from modern non-hominin primates and resemble those of hominins. The interpretation of these footprints is potentially controversial. The print morphology suggests that the trackmaker was a basal member of the Glade Hominini, but as Crete is some distance outside the known geographical range of pre-Pleistocene hominins we must also entertain the possibility that they represent a hitherto unknown late Miocene primate that convergently evolved human-like foot anatomy.

  • 107.
    Goldberg, Amy
    et al.
    Stanford Univ, Dept Biol, Stanford, CA 94305 USA..
    Günther, Torsten
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Rosenberg, Noah A.
    Stanford Univ, Dept Biol, Stanford, CA 94305 USA..
    Jakobsson, Mattias
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ancient X chromosomes reveal contrasting sex bias in Neolithic and Bronze Age Eurasian migrations2017Ingår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 114, nr 10, s. 2657-2662Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Dramatic events in human prehistory, such as the spread of agriculture to Europe from Anatolia and the late Neolithic/Bronze Age migration from the Pontic-Caspian Steppe, can be investigated using patterns of genetic variation among the people who lived in those times. In particular, studies of differing female and male demographic histories on the basis of ancient genomes can provide information about complexities of social structures and cultural interactions in prehistoric populations. We use a mechanistic admixture model to compare the sex-specifically-inherited X chromosome with the autosomes in 20 early Neolithic and 16 late Neolithic/Bronze Age human remains. Contrary to previous hypotheses suggested by the patrilocality of many agricultural populations, we find no evidence of sex-biased admixture during the migration that spread farming across Europe during the early Neolithic. For later migrations from the Pontic Steppe during the late Neolithic/Bronze Age, however, we estimate a dramatic male bias, with approximately five to 14 migrating males for every migrating female. We find evidence of ongoing, primarily male, migration from the steppe to central Europe over a period of multiple generations, with a level of sex bias that excludes a pulse migration during a single generation. The contrasting patterns of sex-specific migration during these two migrations suggest a view of differing cultural histories in which the Neolithic transition was driven by mass migration of both males and females in roughly equal numbers, perhaps whole families, whereas the later Bronze Age migration and cultural shift were instead driven by male migration, potentially connected to new technology and conquest.

  • 108.
    Goldberg, Amy
    et al.
    Stanford Univ, Dept Biol, Stanford, CA 94305 USA..
    Günther, Torsten
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala Univ, Dept Organismal Biol, S-75236 Uppsala, Sweden..
    Rosenberg, Noah A.
    Stanford Univ, Dept Biol, Stanford, CA 94305 USA..
    Jakobsson, Mattias
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Robust model-based inference of male-biased admixture during Bronze Age migration from the Pontic-Caspian Steppe: Reply to Lazaridis and Reich2017Ingår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 114, nr 20, s. E3875-E3877Artikel i tidskrift (Övrigt vetenskapligt)
  • 109. Govindarajan, Annette F.
    et al.
    Källström, Björn
    Selander, Erik
    Östman, Carina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Dahlgren, Thomas G.
    The highly toxic and cryptogenic clinging jellyfish Gonionemus sp. (Hydrozoa, Limnomedusae) on the Swedish west coast2019Ingår i: PeerJ, ISSN 2167-8359, E-ISSN 2167-8359, Vol. 7, artikel-id e6883Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The clinging jellyfish Gonionemus sp. is a small hydromedusa species known historically from the Swedish west coast but not reported in recent times. This species is thought to be native to the northwest Pacific where it is notorious for causing severe stings in humans and is considered invasive or cryptogenic elsewhere. This year, unlike in the past, severe stings in swimmers making contact with Gonionemus sp. medusae occurred in Swedish waters from a sheltered eelgrass bed in the inner Skagerrak archipelago. To the best of our knowledge, this is only the second sting record of Gonionemus sp. from the Northeast Atlantic—with the first record occurring off the Belgian coast in the 1970s. Stinging Gonionemus sp. medusae have also been recently reported from the northwestern Atlantic coast, where, like on the Swedish coast, stings were not reported in the past. We analyzed sea surface temperature data from the past 30 years and show that 2018 had an exceptionally cold spring followed by an exceptionally hot summer. It is suggested that the 2018 temperature anomalies contributed to the Swedish outbreak. An analysis of mitochondrial COI sequences showed that Swedish medusae belong to the same clade as those from toxic populations in the Sea of Japan and northwest Atlantic. Gonionemus sp. is particularly prone to human-mediated dispersal and we suggest that it is possible that this year’s outbreak is the result of anthropogenic factors either through a climate-driven northward range shift or an introduction via shipping activity. We examined medusa growth rates and details of medusa morphology including nematocysts. Two types of penetrating nematocysts: euryteles and b-mastigophores were observed, suggesting that Gonionemus sp. medusae are able to feed on hard-bodied organisms like copepods and cladocerans. Given the now-regular occurrence and regional spread of Gonionemus sp. in the northwest Atlantic, it seems likely that outbreaks in Sweden will continue. More information on its life cycle, dispersal mechanisms, and ecology are thus desirable.

  • 110.
    Grahn, Jessica
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi.
    Blom, Henning
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Ahlberg, Per
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    The primitive antiarch Yunnanolepis from China: a microtomographic study2011Ingår i: Abstracts: The 2nd Wiman meeting : Carl Wiman's Legacy : 100 years of Swedish Palaeontology : Uppsala 17–18 November 2011 / [ed] Benjamin P. Kear and Michael Streng, 2011, s. 8-9Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    Placoderms first appeared during the Silurian, after which they diversified and spread rapidly to dominate the Devonian seas. One of the stratigraphically earliest placoderms is Yunnanolepis, a primitive antiarch from the Early Devonian of China and Vietnam. To date, little specific research has been devoted to yunnanolepids, and previous assessments have utilised conventional descriptive methods. In contrast, this study constructed exceptionally detailed 3D-models based on a synchrotron X-ray microtomographic scan series of Yunnanolepis material from the Muséum National d'Histoire Naturelle, Paris. Our novel data set revealed a well-preserved anterior ventrolateral plate (AVL) with the opening for the pectoral fin, and other hitherto unknown structures such as the transverse crista, postbranchial lamina, and external ornamentation. The first 3D image of the mysterious ’Chang's apparatus’ was also generated. ‘Chang's apparatus’ in known only in Yunnanolepididae, and its function remains unknown. Disarticulated tooth plates and scales of other gnathostomes were also found with the specimen, and include very small AVL plates of young antiarchs. These lack ornamentation and their postbranchial laminae are weakly developed compared to osteologically more mature individuals.

  • 111.
    Günther, Torsten
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Jakobsson, Mattias
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Genes mirror migrations and cultures in prehistoric Europe - a population genomic perspective2016Ingår i: Current Opinion in Genetics and Development, ISSN 0959-437X, E-ISSN 1879-0380, Vol. 41, s. 115-123Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Genomic information from ancient human remains is beginning to show its full potential for learning about human prehistory. We review the last few years' dramatic finds about European prehistory based on genomic data from humans that lived many millennia ago and relate it to modern-day patterns of genomic variation. The early times, the Upper Paleolithic, appears to contain several population turn-overs followed by more stable populations after the Last Glacial Maximum and during the Mesolithic. Some 11 000 years ago the migrations driving the Neolithic transition start from around Anatolia and reach the north and the west of Europe millennia later followed by major migrations during the Bronze Age. These findings show that culture and lifestyle were major determinants of genomic differentiation and similarity in pre-historic Europe rather than geography as is the case today.

  • 112.
    Günther, Torsten
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi. Univ Hohenheim, Inst Plant Breeding Seed Sci & Populat Genet, Stuttgart, Germany.
    Lampei, Christian
    Univ Hohenheim, Inst Plant Breeding Seed Sci & Populat Genet, Stuttgart, Germany..
    Barilar, Ivan
    Univ Hohenheim, Inst Plant Breeding Seed Sci & Populat Genet, Stuttgart, Germany..
    Schmid, Karl J.
    Univ Hohenheim, Inst Plant Breeding Seed Sci & Populat Genet, Stuttgart, Germany..
    Genomic and phenotypic differentiation of Arabidopsis thaliana along altitudinal gradients in the North Italian Alps2016Ingår i: Molecular Ecology, ISSN 0962-1083, E-ISSN 1365-294X, Vol. 25, nr 15, s. 3574-3592Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Altitudinal gradients in mountain regions are short-range clines of different environmental parameters such as temperature or radiation. We investigated genomic and phenotypic signatures of adaptation to such gradients in five Arabidopsis thaliana populations from the North Italian Alps that originated from 580 to 2350m altitude by resequencing pools of 19-29 individuals from each population. The sample includes two pairs of low- and high-altitude populations from two different valleys. High-altitude populations showed a lower nucleotide diversity and negative Tajima's D values and were more closely related to each other than to low-altitude populations from the same valley. Despite their close geographic proximity, demographic analysis revealed that low- and high-altitude populations split between 260000 and 15000years before present. Single nucleotide polymorphisms whose allele frequencies were highly differentiated between low- and high-altitude populations identified genomic regions of up to 50kb length where patterns of genetic diversity are consistent with signatures of local selective sweeps. These regions harbour multiple genes involved in stress response. Variation among populations in two putative adaptive phenotypic traits, frost tolerance and response to light/UV stress was not correlated with altitude. Taken together, the spatial distribution of genetic diversity reflects a potentially adaptive differentiation between low- and high-altitude populations, whereas the phenotypic differentiation in the two traits investigated does not. It may resemble an interaction between adaptation to the local microhabitat and demographic history influenced by historical glaciation cycles, recent seed dispersal and genetic drift in local populations.

  • 113.
    Habicher, Judith
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi. Department of Biomedicine, University of Bergen, Norway.
    Glycosaminoglycan Biosynthesis and Function in Zebrafish Development: Sugars Shaping Skeletons2015Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Heparan sulfate (HS) and chondroitin/dermatan sulfate (CS/DS) proteoglycans are glycosylated proteins with important roles in animal development and homeostasis. HS and CS/DS are long, linear glycosaminoglycan (GAG) polysaccharides and attached to a core protein they form proteoglycans. GAGs on proteoglycans are often modified by sulfate groups and mainly found in the extracellular matrix or associated to the cell membrane. They interact with different proteins, for example signaling molecules, and influence developmental processes. Cells in cartilage produce a functionally specialized dense extracellular matrix, full of proteoglycans. Using the zebrafish as a model to study GAG biosynthesis we discovered that HS production is prioritized over CS/DS production, if the availability of link structures is restricted. We also found that the effects of removing HS and CS/DS biosynthetic enzymes in zebrafish larvae typically differ from what could be hypothesized solely from knowledge of the activity of each enzyme. These findings indicated a highly complex regulation of GAG biosynthesis and we thus proceeded to identify novel GAG biosynthetic enzymes in zebrafish and characterized their expression during early development. Notably, strong expression of CS/DS glycosyltransferases was found in cartilage structures, correlating with a drastic increase of CS/DS synthesis after two days of development, and high CS/DS deposition in cartilage. Finally, to understand how different GAG biosynthetic enzymes affect zebrafish development, we decided to use the CRISPR/Cas9 technology to generate new loss of function alleles for enzymes in HS and CS/DS biosynthesis. Some mutants show disturbed larval development or adult morphology, but we found many mutants to develop into adults without major morphological abnormalities, suggesting a high redundancy for GAG biosynthetic enzymes. Many GAG glycosyltransferases and modification enzymes have multiple isoforms, suggesting that a combination of mutations in one individual will become necessary to study the loss of specific modifications. To conclude, the zebrafish model gives new insights into the GAG machinery and the CRSIPR/Cas9 technology allows for swift production of new loss of function zebrafish lines with defective GAG biosynthesis.

    Delarbeten
    1. On the Roles and Regulation of Chondroitin Sulfate and Heparan Sulfate in Zebrafish Pharyngeal Cartilage Morphogenesis
    Öppna denna publikation i ny flik eller fönster >>On the Roles and Regulation of Chondroitin Sulfate and Heparan Sulfate in Zebrafish Pharyngeal Cartilage Morphogenesis
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    2012 (Engelska)Ingår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 287, nr 40, s. 33905-33916Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The present study addresses the roles of heparan sulfate (HS) proteoglycans and chondroitin sulfate (CS) proteoglycans in the development of zebrafish pharyngeal cartilage structures. uxs1 and b3gat3 mutants, predicted to have impaired biosynthesis of both HS and CS because of defective formation of the common proteoglycan linkage tetrasaccharide were analyzed along with ext2 and extl3 mutants, predicted to have defective HS polymerization. Notably, the effects on HS and CS biosynthesis in the respective mutant strains were shown to differ from what had been hypothesized. In uxs1 and b3gat3 mutant larvae, biosynthesis of CS was shown to be virtually abolished, whereas these mutants still were capable of synthesizing 50% of the HS produced in control larvae. extl3 and ext2 mutants on the other hand were shown to synthesize reduced amounts of hypersulfated HS. Further, extl3 mutants produced higher levels of CS than control larvae, whereas morpholino-mediated suppression of csgalnact1/csgalnact2 resulted in increased HS biosynthesis. Thus, the balance of the Extl3 and Csgalnact1/Csgalnact2 proteins influences the HS/CS ratio. A characterization of the pharyngeal cartilage element morphologies in the single mutant strains, as well as in ext2;uxs1 double mutants, was conducted. A correlation between HS and CS production and phenotypes was found, such that impaired HS biosynthesis was shown to affect chondrocyte intercalation, whereas impaired CS biosynthesis inhibited formation of the extracellular matrix surrounding chondrocytes.

    Nyckelord
    Protein Linkage Region, Molecular-Cloning, Hspg Synthesis, Cell Polarity, Growth-Plate, Expression, Ext2, Proteoglycans, Glypican, Xylose
    Nationell ämneskategori
    Naturvetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-185209 (URN)10.1074/jbc.M112.401646 (DOI)000309602100071 ()
    Anmärkning

    De två första författarna delar förstaförfattarskapet.

    De två sista författarna delar sistaförfattarskapet.

    Tillgänglig från: 2012-11-22 Skapad: 2012-11-21 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
    2. Expression of chondroitin/dermatan sulfate glycosyltransferases during early zebrafish development
    Öppna denna publikation i ny flik eller fönster >>Expression of chondroitin/dermatan sulfate glycosyltransferases during early zebrafish development
    Visa övriga...
    2013 (Engelska)Ingår i: Developmental Dynamics, ISSN 1058-8388, E-ISSN 1097-0177, Vol. 242, nr 8, s. 964-975Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background: Chondroitin/dermatan sulfate (CS/DS) proteoglycans present in the extracellular matrix have important structural and regulatory functions. Results: Six human genes have previously been shown to catalyze CS/DS polymerization. Here we show that one of these genes, chpf, is represented by two copies in the zebrafish genome, chpfa and chpfb, while the other five human CS/DS glycosyltransferases csgalnact1, csgalnact2, chpf2, chsy1, and chsy3 all have single zebrafish orthologues. The putative zebrafish CS/DS glycosyltransferases are spatially and temporally expressed. Interestingly, overlapping expression of multiple glycosyltransferases coincides with high CS/DS deposition. Finally, whereas the relative levels of the related polysaccharide HS reach steady-state at around 2 days post fertilization, there is a continued relative increase of the CS amounts per larvae during the first 6 days of development, matching the increased cartilage formation. Conclusions: There are 7 CS/DS glycosyltransferases in zebrafish, which, based on homology, can be divided into the CSGALNACT, CHSY, and CHPF families. The overlap between intense CS/DS production and the expression of multiple CS/DS glycosyltransferases suggests that efficient CS/DS biosynthesis requires a combination of several glycosyltransferases.

    Nyckelord
    chondroitin sulfate, polymerase, CSGALNACT, CHSY, CHPF, zebrafish
    Nationell ämneskategori
    Naturvetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-204834 (URN)10.1002/dvdy.23981 (DOI)000321843400008 ()
    Anmärkning

    De två (2) första författarna delar förstaförfattarskapet.

    Tillgänglig från: 2013-08-13 Skapad: 2013-08-12 Senast uppdaterad: 2017-12-06Bibliografiskt granskad
    3. Chondroitin / Dermatan Sulfate Modification Enzymes in Zebrafish Development
    Öppna denna publikation i ny flik eller fönster >>Chondroitin / Dermatan Sulfate Modification Enzymes in Zebrafish Development
    Visa övriga...
    2015 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 3, artikel-id e0121957Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Chondroitin/dermatan sulfate (CS/DS) proteoglycans consist of unbranched sulfated polysaccharide chains of repeating GalNAc-GlcA/IdoA disaccharide units, attached to serine residues on specific proteins. The CS/DS proteoglycans are abundant in the extracellular matrix where they have essential functions in tissue development and homeostasis. In this report a phylogenetic analysis of vertebrate genes coding for the enzymes that modify CS/DS is presented. We identify single orthologous genes in the zebrafish genome for the sulfotransferases chst7, chst11, chst13, chst14, chst15 and ust and the epimerase dse. In contrast, two copies were found for mammalian sulfotransferases CHST3 and CHST12 and the epimerase DSEL, named chst3a and chst3b, chst12a and chst12b, dsela and dselb, respectively. Expression of CS/DS modification enzymes is spatially and temporally regulated with a large variation between different genes. We found that CS/DS 4-O-sulfotransferases and 6-O-sulfotransferases as well as CS/DS epimerases show a strong and partly overlapping expression, whereas the expression is restricted for enzymes with ability to synthesize di-sulfated disaccharides. A structural analysis further showed that CS/DS sulfation increases during embryonic development mainly due to synthesis of 4-O-sulfated GalNAc while the proportion of 6-O-sulfated GalNAc increases in later developmental stages. Di-sulfated GalNAc synthesized by Chst15 and 2-O-sulfated GlcA/IdoA synthesized by Ust are rare, in accordance with the restricted expression of these enzymes. We also compared CS/DS composition with that of heparan sulfate (HS). Notably, CS/DS biosynthesis in early zebrafish development is more dynamic than HS biosynthesis. Furthermore, HS contains disaccharides with more than one sulfate group, which are virtually absent in CS/DS.

    Nationell ämneskategori
    Evolutionsbiologi
    Identifikatorer
    urn:nbn:se:uu:diva-252231 (URN)10.1371/journal.pone.0121957 (DOI)000352083900161 ()25793894 (PubMedID)
    Tillgänglig från: 2015-05-05 Skapad: 2015-05-04 Senast uppdaterad: 2017-12-04Bibliografiskt granskad
    4. The Ndst Gene Family in Zebrafish: Role of Ndst1b in Pharyngeal Arch Formation
    Öppna denna publikation i ny flik eller fönster >>The Ndst Gene Family in Zebrafish: Role of Ndst1b in Pharyngeal Arch Formation
    Visa övriga...
    2015 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 3Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Heparan sulfate (HS) proteoglycans are ubiquitous components of the extracellular matrix and plasma membrane of metazoans. The sulfation pattern of the HS glycosaminoglycan chain is characteristic for each tissue and changes during development. The glucosaminyl N-deacetylase/N-sulfotransferase (NDST) enzymes catalyze N-deacetylation and N-sulfation during HS biosynthesis and have a key role in designing the sulfation pattern. We here report on the presence of five NDST genes in zebrafish. Zebrafish ndst1a, ndst1b, ndst2a and ndst2b represent duplicated mammalian orthologues of NDST1 and NDST2 that arose through teleost specific genome duplication. Interestingly, the single zebrafish orthologue ndst3, is equally similar to tetrapod Ndst3 and Ndst4. It is likely that a local duplication in the common ancestor of lobe-finned fish and tetrapods gave rise to these two genes. All zebrafish Ndst genes showed distinct but partially overlapping expression patterns during embryonic development. Morpholino knockdown of ndst1b resulted in delayed development, craniofacial cartilage abnormalities, shortened body and pectoral fin length, resembling some of the features of the Ndst1 mouse knockout.

    Nationell ämneskategori
    Evolutionsbiologi Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
    Identifikatorer
    urn:nbn:se:uu:diva-251802 (URN)10.1371/journal.pone.0119040 (DOI)000351277500060 ()25767878 (PubMedID)
    Tillgänglig från: 2015-04-28 Skapad: 2015-04-24 Senast uppdaterad: 2017-12-04Bibliografiskt granskad
    5. Large-scale generation of zebrafish mutants with defective glycosaminoglycan biosynthesis
    Öppna denna publikation i ny flik eller fönster >>Large-scale generation of zebrafish mutants with defective glycosaminoglycan biosynthesis
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Utvecklingsbiologi Biokemi och molekylärbiologi
    Identifikatorer
    urn:nbn:se:uu:diva-258588 (URN)
    Tillgänglig från: 2015-07-27 Skapad: 2015-07-16 Senast uppdaterad: 2015-11-10
  • 114.
    Habicher, Judith
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    The role of the extracellular matrix in zebrafish cartilage development2013Licentiatavhandling, sammanläggning (Övrigt vetenskapligt)
    Delarbeten
    1. On the Roles and Regulation of Chondroitin Sulfate and Heparan Sulfate in Zebrafish Pharyngeal Cartilage Morphogenesis
    Öppna denna publikation i ny flik eller fönster >>On the Roles and Regulation of Chondroitin Sulfate and Heparan Sulfate in Zebrafish Pharyngeal Cartilage Morphogenesis
    Visa övriga...
    2012 (Engelska)Ingår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 287, nr 40, s. 33905-33916Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The present study addresses the roles of heparan sulfate (HS) proteoglycans and chondroitin sulfate (CS) proteoglycans in the development of zebrafish pharyngeal cartilage structures. uxs1 and b3gat3 mutants, predicted to have impaired biosynthesis of both HS and CS because of defective formation of the common proteoglycan linkage tetrasaccharide were analyzed along with ext2 and extl3 mutants, predicted to have defective HS polymerization. Notably, the effects on HS and CS biosynthesis in the respective mutant strains were shown to differ from what had been hypothesized. In uxs1 and b3gat3 mutant larvae, biosynthesis of CS was shown to be virtually abolished, whereas these mutants still were capable of synthesizing 50% of the HS produced in control larvae. extl3 and ext2 mutants on the other hand were shown to synthesize reduced amounts of hypersulfated HS. Further, extl3 mutants produced higher levels of CS than control larvae, whereas morpholino-mediated suppression of csgalnact1/csgalnact2 resulted in increased HS biosynthesis. Thus, the balance of the Extl3 and Csgalnact1/Csgalnact2 proteins influences the HS/CS ratio. A characterization of the pharyngeal cartilage element morphologies in the single mutant strains, as well as in ext2;uxs1 double mutants, was conducted. A correlation between HS and CS production and phenotypes was found, such that impaired HS biosynthesis was shown to affect chondrocyte intercalation, whereas impaired CS biosynthesis inhibited formation of the extracellular matrix surrounding chondrocytes.

    Nyckelord
    Protein Linkage Region, Molecular-Cloning, Hspg Synthesis, Cell Polarity, Growth-Plate, Expression, Ext2, Proteoglycans, Glypican, Xylose
    Nationell ämneskategori
    Naturvetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-185209 (URN)10.1074/jbc.M112.401646 (DOI)000309602100071 ()
    Anmärkning

    De två första författarna delar förstaförfattarskapet.

    De två sista författarna delar sistaförfattarskapet.

    Tillgänglig från: 2012-11-22 Skapad: 2012-11-21 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
    2. Spinal Deformity in Aged Zebrafish Is Accompanied by Degenerative Changes to Their Vertebrae that Resemble Osteoarthritis
    Öppna denna publikation i ny flik eller fönster >>Spinal Deformity in Aged Zebrafish Is Accompanied by Degenerative Changes to Their Vertebrae that Resemble Osteoarthritis
    Visa övriga...
    2013 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 9, s. e75787-Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Age-related degenerative changes within the vertebral column are a significant cause of morbidity with considerable socio-economic impact worldwide. An improved understanding of these changes through the development of experimental models may lead to improvements in existing clinical treatment options. The zebrafish is a well-established model for the study of skeletogenesis with significant potential in gerontological research. With advancing age, zebrafish frequently develop gross deformities of their vertebral column, previously ascribed to reduced trunk muscle tone. In this study, we assess degenerative changes specifically within the bone and cartilage of the vertebral column of zebrafish at 1, 2 and 3-years of age. We show increased frequency and severity of spinal deformities/curvatures with age. Underlying the most severe phenotypes are partial or complete vertebral dislocations and focal thickening of the vertebral bone at the joint margins. MicroCT examination demonstrates small defects, fractures and morphological evidence suggestive of bone erosion and remodeling (i.e. osteophytes) within the vertebrae during aging, but no significant change in bone density. Light and electron microscopic examination reveal striking agerelated changes in cell morphology, suggestive of chondroptosis, and tissue remodelling of the vertebral cartilage, particularly within the pericellular micro-environment. Glycosaminoglycan analysis of the vertebral column by HPLC demonstrates a consistent, age-related increase in the yield of total chondroitin sulfate disaccharide, but no change in sulfation pattern, supported by immunohistochemical analysis. Immunohistochemistry strongly identifies all three chondroitin/dermatan sulphate isoforms (C-0-S, C-4-S/DS and C-6-S) within the vertebral cartilage, particularly within the pericellular micro-environment. In contrast, keratan sulfate immunolocalises specifically with the notochordal tissue of the intervertebral disc, and its labelling diminishes with age. In summary, these observations raise the prospect that zebrafish, in addition to modelling skeletal development, may have utility in modelling age-related degenerative changes that affect the skeleton during senescence.

    Nationell ämneskategori
    Naturvetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-210236 (URN)10.1371/journal.pone.0075787 (DOI)000325025200062 ()
    Tillgänglig från: 2013-11-05 Skapad: 2013-11-04 Senast uppdaterad: 2017-12-06Bibliografiskt granskad
    3. Expression of chondroitin/dermatan sulfate glycosyltransferases during early zebrafish development
    Öppna denna publikation i ny flik eller fönster >>Expression of chondroitin/dermatan sulfate glycosyltransferases during early zebrafish development
    Visa övriga...
    2013 (Engelska)Ingår i: Developmental Dynamics, ISSN 1058-8388, E-ISSN 1097-0177, Vol. 242, nr 8, s. 964-975Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background: Chondroitin/dermatan sulfate (CS/DS) proteoglycans present in the extracellular matrix have important structural and regulatory functions. Results: Six human genes have previously been shown to catalyze CS/DS polymerization. Here we show that one of these genes, chpf, is represented by two copies in the zebrafish genome, chpfa and chpfb, while the other five human CS/DS glycosyltransferases csgalnact1, csgalnact2, chpf2, chsy1, and chsy3 all have single zebrafish orthologues. The putative zebrafish CS/DS glycosyltransferases are spatially and temporally expressed. Interestingly, overlapping expression of multiple glycosyltransferases coincides with high CS/DS deposition. Finally, whereas the relative levels of the related polysaccharide HS reach steady-state at around 2 days post fertilization, there is a continued relative increase of the CS amounts per larvae during the first 6 days of development, matching the increased cartilage formation. Conclusions: There are 7 CS/DS glycosyltransferases in zebrafish, which, based on homology, can be divided into the CSGALNACT, CHSY, and CHPF families. The overlap between intense CS/DS production and the expression of multiple CS/DS glycosyltransferases suggests that efficient CS/DS biosynthesis requires a combination of several glycosyltransferases.

    Nyckelord
    chondroitin sulfate, polymerase, CSGALNACT, CHSY, CHPF, zebrafish
    Nationell ämneskategori
    Naturvetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-204834 (URN)10.1002/dvdy.23981 (DOI)000321843400008 ()
    Anmärkning

    De två (2) första författarna delar förstaförfattarskapet.

    Tillgänglig från: 2013-08-13 Skapad: 2013-08-12 Senast uppdaterad: 2017-12-06Bibliografiskt granskad
  • 115.
    Habicher, Judith
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Haitina, Tatjana
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Eriksson, Inger
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Holmborn, Katarina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Dierker, Tabea
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Ahlberg, Per E.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Ledin, Johan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Chondroitin / Dermatan Sulfate Modification Enzymes in Zebrafish Development2015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 3, artikel-id e0121957Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Chondroitin/dermatan sulfate (CS/DS) proteoglycans consist of unbranched sulfated polysaccharide chains of repeating GalNAc-GlcA/IdoA disaccharide units, attached to serine residues on specific proteins. The CS/DS proteoglycans are abundant in the extracellular matrix where they have essential functions in tissue development and homeostasis. In this report a phylogenetic analysis of vertebrate genes coding for the enzymes that modify CS/DS is presented. We identify single orthologous genes in the zebrafish genome for the sulfotransferases chst7, chst11, chst13, chst14, chst15 and ust and the epimerase dse. In contrast, two copies were found for mammalian sulfotransferases CHST3 and CHST12 and the epimerase DSEL, named chst3a and chst3b, chst12a and chst12b, dsela and dselb, respectively. Expression of CS/DS modification enzymes is spatially and temporally regulated with a large variation between different genes. We found that CS/DS 4-O-sulfotransferases and 6-O-sulfotransferases as well as CS/DS epimerases show a strong and partly overlapping expression, whereas the expression is restricted for enzymes with ability to synthesize di-sulfated disaccharides. A structural analysis further showed that CS/DS sulfation increases during embryonic development mainly due to synthesis of 4-O-sulfated GalNAc while the proportion of 6-O-sulfated GalNAc increases in later developmental stages. Di-sulfated GalNAc synthesized by Chst15 and 2-O-sulfated GlcA/IdoA synthesized by Ust are rare, in accordance with the restricted expression of these enzymes. We also compared CS/DS composition with that of heparan sulfate (HS). Notably, CS/DS biosynthesis in early zebrafish development is more dynamic than HS biosynthesis. Furthermore, HS contains disaccharides with more than one sulfate group, which are virtually absent in CS/DS.

  • 116. Hairapetian, Vachik
    et al.
    Blom, Henning
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Turner, Susan
    Early Frasnian thelodont scales from central Iran and their implications for turiniid taxonomy, systematics and distribution2016Ingår i: Journal of Vertebrate Paleontology, ISSN 0272-4634, E-ISSN 1937-2809, Vol. 36, nr 3, artikel-id e1100632Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We describe isolated shark teeth collected in levels of the Calafate Formation (Maastrichtian, Late Cretaceous) on the southeast coast of Argentino Lake, Calafate City, Santa Cruz Province, Argentina. The teeth belong to the hexanchiform Notidanodon dentatus, a new species of the squaliform Protosqualus, and an indeterminate species of the echinorhiniform genus Echinorhinus. The record of Notidanodon constitutes the first in South America. The report of Notidanodon associated with plesiosaur remains is in accordance with previous records from around the world. Protosqualus argentinensis, nov. sp., which is the first record of the genus in South America, is characterized by having teeth with a apicobasally tall root and serrated cutting edges, among other features.Echinorhinus sp. constitutes one of the oldest records of this genus on the continent and one of the few Mesozoic records worldwide. This shark association is clearly distinct from coeval selachian faunas from northern Patagonia, which exhibit clear Tethyan influences. Instead, it shows some similarities to other high-latitude selachian faunas, including Australia, New Zealand, and Antarctica. It is possible that the Cretaceous selachian assemblages of Patagonia may be separated into two different associations: northern Patagonian faunas are related to more temperate associations of lower paleolatitudes, whereas those of southern Patagonia are closer to other southern localities.

  • 117.
    Haitina, Tatjana
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Molecular mechanism of articular cartilage establishment during the evolution of vertebrates2017Konferensbidrag (Refereegranskat)
  • 118.
    Haitina, Tatjana
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Regulation of genes involved in the development of the pharyngeal arches2011Ingår i: Regulation of genes involved in the development of the pharyngeal arches, 2011Konferensbidrag (Övrigt vetenskapligt)
  • 119.
    Haitina, Tatjana
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    The role of transcription factors during the development of craniofacial tendons and ligaments2016Konferensbidrag (Refereegranskat)
  • 120.
    Haitina, Tatjana
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Qu, Qinming
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Ahlberg, Per
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Identification of enamel matrix protein genes in the genome of spotted gar Lepisosteus oculatus 2015Konferensbidrag (Övrigt vetenskapligt)
  • 121. Hayes, Anthony J.
    et al.
    Reynolds, Scott
    Nowell, Mari A.
    Meakin, Lee B.
    Habicher, Judith
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Ledin, Johan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Bashford, Andrew
    Caterson, Bruce
    Hammond, Chrissy L.
    Spinal Deformity in Aged Zebrafish Is Accompanied by Degenerative Changes to Their Vertebrae that Resemble Osteoarthritis2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 9, s. e75787-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Age-related degenerative changes within the vertebral column are a significant cause of morbidity with considerable socio-economic impact worldwide. An improved understanding of these changes through the development of experimental models may lead to improvements in existing clinical treatment options. The zebrafish is a well-established model for the study of skeletogenesis with significant potential in gerontological research. With advancing age, zebrafish frequently develop gross deformities of their vertebral column, previously ascribed to reduced trunk muscle tone. In this study, we assess degenerative changes specifically within the bone and cartilage of the vertebral column of zebrafish at 1, 2 and 3-years of age. We show increased frequency and severity of spinal deformities/curvatures with age. Underlying the most severe phenotypes are partial or complete vertebral dislocations and focal thickening of the vertebral bone at the joint margins. MicroCT examination demonstrates small defects, fractures and morphological evidence suggestive of bone erosion and remodeling (i.e. osteophytes) within the vertebrae during aging, but no significant change in bone density. Light and electron microscopic examination reveal striking agerelated changes in cell morphology, suggestive of chondroptosis, and tissue remodelling of the vertebral cartilage, particularly within the pericellular micro-environment. Glycosaminoglycan analysis of the vertebral column by HPLC demonstrates a consistent, age-related increase in the yield of total chondroitin sulfate disaccharide, but no change in sulfation pattern, supported by immunohistochemical analysis. Immunohistochemistry strongly identifies all three chondroitin/dermatan sulphate isoforms (C-0-S, C-4-S/DS and C-6-S) within the vertebral cartilage, particularly within the pericellular micro-environment. In contrast, keratan sulfate immunolocalises specifically with the notochordal tissue of the intervertebral disc, and its labelling diminishes with age. In summary, these observations raise the prospect that zebrafish, in addition to modelling skeletal development, may have utility in modelling age-related degenerative changes that affect the skeleton during senescence.

  • 122.
    Hedenstierna-Jonson, Charlotte
    et al.
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Historisk-filosofiska fakulteten, Institutionen för arkeologi och antik historia, Arkeologi. Archaeological Research Laboratory, Department of Archaeology and Classical Studies, Stockholm University, Stockholm, Sweden.
    Kjellström, Anna
    Archaeological Research Laboratory, Department of Archaeology and Classical Studies, Stockholm University, Stockholm, Sweden; Osteoarchaeological Research Laboratory, Department of Archaeology and Classical Studies, Stockholm University, Stockholm, Sweden .
    Zachrisson, Torun
    Archaeological Research Laboratory, Department of Archaeology and Classical Studies, Stockholm University, Stockholm, Sweden.
    Krzewińska, Maja
    Archaeological Research Laboratory, Department of Archaeology and Classical Studies, Stockholm University, Stockholm, Sweden.
    Sobrado, Veronica
    Archaeological Research Laboratory, Department of Archaeology and Classical Studies, Stockholm University, Stockholm, Sweden.
    Price, Neil
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Historisk-filosofiska fakulteten, Institutionen för arkeologi och antik historia, Arkeologi.
    Günther, Torsten
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Jakobsson, Mattias
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Götherström, Anders
    Archaeological Research Laboratory, Department of Archaeology and Classical Studies, Stockholm University, Stockholm, Sweden.
    Storå, Jan
    Osteoarchaeological Research Laboratory, Department of Archaeology and Classical Studies, Stockholm University, Stockholm, Sweden.
    A female Viking warrior confirmed by genomics2017Ingår i: American Journal of Physical Anthropology, ISSN 0002-9483, E-ISSN 1096-8644, Vol. 164, nr 4, s. 853-860Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: The objective of this study has been to confirm the sex and the affinity of an individual buried in a well-furnished warrior grave (Bj 581) in the Viking Age town of Birka, Sweden. Previously, based on the material and historical records, the male sex has been associated with the gender of the warrior and such was the case with Bj 581. An earlier osteological classification of the individual as female was considered controversial in a historical and archaeological context. A genomic confirmation of the biological sex of the individual was considered necessary to solve the issue.

    MATERIALS AND METHODS: Genome-wide sequence data was generated in order to confirm the biological sex, to support skeletal integrity, and to investigate the genetic relationship of the individual to ancient individuals as well as modern-day groups. Additionally, a strontium isotope analysis was conducted to highlight the mobility of the individual.

    RESULTS: The genomic results revealed the lack of a Y-chromosome and thus a female biological sex, and the mtDNA analyses support a single-individual origin of sampled elements. The genetic affinity is close to present-day North Europeans, and within Sweden to the southern and south-central region. Nevertheless, the Sr values are not conclusive as to whether she was of local or nonlocal origin.

    DISCUSSION: The identification of a female Viking warrior provides a unique insight into the Viking society, social constructions, and exceptions to the norm in the Viking time-period. The results call for caution against generalizations regarding social orders in past societies.

  • 123.
    Herbin, Marc
    et al.
    Muséum National d'Histoire Naturelle, Paris, France.
    Dupret, Vincent
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Goussard, Florent
    Muséum National d'Histoire Naturelle, paris, France.
    Clément, Gaël
    Muséum National d'Histoire Naturelle, Paris, France.
    Les techniques d’imagerie 3D au service de la valorisation scientifique des collections anatomiques2010Ingår i: La Lettre de l'OCIM, ISSN 0994-1908, Vol. 131, s. 13-18Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The presentation of this virtual study of the anatomy of a Coelacanthe specimen produced using three dimensional x ray imaging and magnetic resonance notably brings light to the possibilities of application of these technologies – which avoid repetitive manipulations and preserve the morphological integrity of precious and scientifically important specimens – in the field of scenography or of preventive conservation.

  • 124.
    Hervella, M.
    et al.
    Univ Basque Country UPV EHU, Dept Genet Phys Anthropol & Anim Physiol, Barrio Sarriena S-N, Leioa 48940, Bizkaia, Spain..
    Svensson, Emma M.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Alberdi, A.
    Univ Copenhagen, Nat Hist Museum Denmark, Oster Voldgade 5-7, DK-1350 Copenhagen, Denmark..
    Günther, Torsten
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Izagirre, N.
    Univ Basque Country UPV EHU, Dept Genet Phys Anthropol & Anim Physiol, Barrio Sarriena S-N, Leioa 48940, Bizkaia, Spain..
    Munters, Arielle R.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Alonso, S.
    Univ Basque Country UPV EHU, Dept Genet Phys Anthropol & Anim Physiol, Barrio Sarriena S-N, Leioa 48940, Bizkaia, Spain..
    Ioana, M.
    Univ Med & Pharm Craiova, Human Genom Lab, Bvd 1 Mai 66, Craiova, Romania.;Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, NL-6525 ED Nijmegen, Netherlands.;Radboud Univ Nijmegen, Med Ctr, Radboud Ctr Infect Dis, NL-6525 ED Nijmegen, Netherlands..
    Ridiche, F.
    Museum Oltenia, Hist & Archaeol Dept, Madona Dudu Str 14, Craiova, Romania..
    Soficaru, A.
    Romanian Acad, Fr J Rainer Inst Anthropol, Eroii Sanitari 8,POB 35-13, Bucharest, Romania..
    Jakobsson, Mattias
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Netea, M. G.
    Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, NL-6525 ED Nijmegen, Netherlands.;Radboud Univ Nijmegen, Med Ctr, Radboud Ctr Infect Dis, NL-6525 ED Nijmegen, Netherlands..
    de-la-Rua, C.
    Univ Basque Country UPV EHU, Dept Genet Phys Anthropol & Anim Physiol, Barrio Sarriena S-N, Leioa 48940, Bizkaia, Spain..
    The mitogenome of a 35,000-year-old Homo sapiens from Europe supports a Palaeolithic back-migration to Africa2016Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, artikel-id 25501Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    After the dispersal of modern humans (Homo sapiens) Out of Africa, hominins with a similar morphology to that of present-day humans initiated the gradual demographic expansion into Eurasia. The mitogenome (33-fold coverage) of the Pestera Muierii 1 individual (PM1) from Romania (35 ky cal BP) we present in this article corresponds fully to Homo sapiens, whilst exhibiting a mosaic of morphological features related to both modern humans and Neandertals. We have identified the PM1 mitogenome as a basal haplogroup U6*, not previously found in any ancient or present-day humans. The derived U6 haplotypes are predominantly found in present-day North-Western African populations. Concomitantly, those found in Europe have been attributed to recent gene-flow from North Africa. The presence of the basal haplogroup U6* in South East Europe (Romania) at 35 ky BP confirms a Eurasian origin of the U6 mitochondrial lineage. Consequently, we propose that the PM1 lineage is an offshoot to South East Europe that can be traced to the Early Upper Paleolithic back migration from Western Asia to North Africa, during which the U6 lineage diversified, until the emergence of the present-day U6 African lineages.

  • 125.
    Histon, Kathleen
    et al.
    University of Modena.
    Zigaite, Zivile
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Preface2015Ingår i: Estonian journal of earth sciences, ISSN 1736-4728, E-ISSN 1736-7557, Vol. 64, nr 1, s. 1-2Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Evolutionary palaeoecology and palaeobiogeography: year 4 of the IGCP-591 project 'The Early to Middle Palaeozoic Revolution - Bridging the Gap between the Great Ordovician Biodiversification Event and the Devonian Terrestrial Revolution

  • 126.
    Holland, Linda Z.
    et al.
    Univ Calif San Diego, Scripps Inst Oceanog, Marine Biol Res Div, La Jolla, CA 92093 USA.
    Ocampo Daza, Daniel
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi. Univ Calif Merced, Sch Nat Sci, Merced, CA 95343 USA.
    A new look at an old question: when did the second whole genome duplication occur in vertebrate evolution?2018Ingår i: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 19, artikel-id 209Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A recent study used 61 extant animal genomes to reconstruct the chromosomes of the hypothetical amniote ancestor. Comparison of this karyotype to the 17 chordate linkage groups previously inferred in the ancestral chordate indicated that two whole genome duplications probably occurred in the lineage preceding the ancestral vertebrate.

  • 127.
    Hollfelder, Nina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Population genetic history and patterns of admixture: Examples from northeastern and southern Africa2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The origin of humans lies in Africa, as has been shown by archaeology, paleontology and genetics. Here, we can find the largest genetic diversity and the deepest split among human populations. African genetic diversity has been shaped by a long and complex history. In this thesis, I applied population genomic methods to investigate different aspects of the demographic history of Africa, specifically northeast and southern Africa.

    Both of these regions are population melting-pots, with many historically known major migrations.

    In northeast African populations, Eurasian admixture in central, northern, and eastern Sudanese populations was identified to be of Middle Eastern origin and the admixture time coincides with the Arab expansion. In northeast Africa I also studied alleles associated with lactase persistence, the ability to digest milk at an adult age. A wide diversity of these alleles was detected in Sudan, most commonly among pastoralists. The presence of a Middle Eastern LP-allele and absence of a European LP-allele is consistent with the admixture pattern observed in the first paper.

    I deciphered the patterns of genetic admixture in the Afrikaner population of South Africa and compared admixture patterns of the X-chromosome and autosomes to disentangle sex-biased admixture in southern African populations.

    The Afrikaner were shown to carry on average 5% non-European admixture, mostly from Khoe-San, East and South Asian sources. The admixture was sex-biased, with larger contributions from European males and admixture with Africans can be dated to 9-10 generations ago – fitting previous genealogical estimates of the age and the history of the population.

    Bantu-speaker/Khoe-San contact shows a pattern of female Bantu-speaker bias, which is conflicting with previous mtDNA and Y-chromosome studies. A change in mate-choice over time could explain this discrepancy.

    This thesis contributes to a deeper understanding of African demographic history in general and of some previously understudied populations and geographic areas in particular.

    Delarbeten
    1. Northeast African genomic variation shaped by the continuity of indigenous groups and Eurasian migrations
    Öppna denna publikation i ny flik eller fönster >>Northeast African genomic variation shaped by the continuity of indigenous groups and Eurasian migrations
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    2017 (Engelska)Ingår i: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 13, nr 8, artikel-id e1006976Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Northeast Africa has a long history of human habitation, with fossil-finds from the earliest anatomically modern humans, and housing ancient civilizations. The region is also the gateway out of Africa, as well as a portal for migration into Africa from Eurasia via the Middle East and the Arabian Peninsula. We investigate the population history of northeast Africa by genotyping similar to 3.9 million SNPs in 221 individuals from 18 populations sampled in Sudan and South Sudan and combine this data with published genome-wide data from surrounding areas. We find a strong genetic divide between the populations from the northeastern parts of the region (Nubians, central Arab populations, and the Beja) and populations towards the west and south (Nilotes, Darfur and Kordofan populations). This differentiation is mainly caused by a large Eurasian ancestry component of the northeast populations likely driven by migration of Middle Eastern groups followed by admixture that affected the local populations in a north-to-south succession of events. Genetic evidence points to an early admixture event in the Nubians, concurrent with historical contact between North Sudanese and Arab groups. We estimate the admixture in current-day Sudanese Arab populations to about 700 years ago, coinciding with the fall of Dongola in 1315/1316 AD, a wave of admixture that reached the Darfurian/Kordofanian populations some 400-200 years ago. In contrast to the northeastern populations, the current-day Nilotic populations from the south of the region display little or no admixture from Eurasian groups indicating long-term isolation and population continuity in these areas of northeast Africa.

    Ort, förlag, år, upplaga, sidor
    PUBLIC LIBRARY SCIENCE, 2017
    Nationell ämneskategori
    Genetik Evolutionsbiologi
    Identifikatorer
    urn:nbn:se:uu:diva-333162 (URN)10.1371/journal.pgen.1006976 (DOI)000408763800042 ()28837655 (PubMedID)
    Tillgänglig från: 2017-11-07 Skapad: 2017-11-07 Senast uppdaterad: 2017-12-13Bibliografiskt granskad
    2. The genetic variation of lactase persistence alleles in northeast Africa
    Öppna denna publikation i ny flik eller fönster >>The genetic variation of lactase persistence alleles in northeast Africa
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    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Evolutionsbiologi Genetik
    Identifikatorer
    urn:nbn:se:uu:diva-336177 (URN)
    Tillgänglig från: 2017-12-12 Skapad: 2017-12-12 Senast uppdaterad: 2017-12-13
    3. Patterns of African and Asian admixture in the Afrikaner population of South Africa
    Öppna denna publikation i ny flik eller fönster >>Patterns of African and Asian admixture in the Afrikaner population of South Africa
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