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  • 1.
    Agnvall, Beatrix
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska fakulteten.
    Jensen, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska fakulteten.
    Effects of Divergent Selection for Fear of Humans on Behaviour in Red Junglefowl2016Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 11, 1-12 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Domestication has caused a range of similar phenotypic changes across taxa, relating to physiology, morphology and behaviour. It has been suggested that this recurring domesticated phenotype may be a result of correlated responses to a central trait, namely increased tameness. We selected Red Junglefowl, the ancestors of domesticated chickens, during five generations for reduced fear of humans. This caused a marked and significant response in tameness, and previous studies have found correlated effects on growth, metabolism, reproduction, and some behaviour not directly selected for. Here, we report the results from a series of behavioural tests carried out on the initial parental generation (P0) and the fifth selected generation (S5), focusing on behaviour not functionally related to tameness, in order to study any correlated effects. Birds were tested for fear of humans, social reinstatement tendency, open field behaviour at two different ages, foraging/exploration, response to a simulated aerial predator attack and tonic immobility. In S5, there were no effects of selection on foraging/exploration or tonic immobility, while in the social reinstatement and open field tests there were significant interactions between selection and sex. In the aerial predator test, there were significant main effects of selection, indicating that fear of humans may represent a general wariness towards predators. In conclusion, we found only small correlated effects on behaviours not related to the tameness trait selected for, in spite of them showing high genetic correlations to fear of humans in a previous study on the same population. This suggests that species-specific behaviour is generally resilient to changes during domestication.

  • 2.
    Aguilo, Francesca
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap. Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
    Zakirova, Zuchra
    Nolan, Katie
    Wagner, Ryan
    Sharma, Rajal
    Hogan, Megan
    Wei, Chengguo
    Sun, Yifei
    Walsh, Martin J.
    Kelley, Kevin
    Zhang, Weijia
    Ozelius, Laurie J.
    Gonzalez-Alegre, Pedro
    Zwaka, Thomas P.
    Ehrlich, Michelle E.
    THAP1: Role in Mouse Embryonic Stem Cell Survival and Differentiation2017Inngår i: Stem Cell Reports, ISSN 2213-6711, Vol. 9, nr 1, 92-107 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    THAP1 (THAP [Thanatos-associated protein] domain-containing, apoptosis-associated protein 1) is a ubiquitously expressed member of a family of transcription factors with highly conserved DNA-binding and protein-interacting regions. Mutations in THAP1 cause dystonia, DYT6, a neurologic movement disorder. THAP1 downstream targets and the mechanism via which it causes dystonia are largely unknown. Here, we show that wild-type THAP1 regulates embryonic stem cell (ESC) potential, survival, and proliferation. Our findings identify THAP1 as an essential factor underlying mouse ESC survival and to some extent, differentiation, particularly neuroectodermal. Loss of THAP1 or replacement with a disease-causing mutation results in an enhanced rate of cell death, prolongs Nanog, Prdm14, and/or Rex1 expression upon differentiation, and results in failure to upregulate ectodermal genes. ChIP-Seq reveals that these activities are likely due in part to indirect regulation of gene expression.

  • 3.
    Ahlberg, Per E.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Evolutionär organismbiologi.
    Blom, Henning
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Evolutionär organismbiologi.
    Brazeau, Martin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Evolutionär organismbiologi.
    Clément, Gaël
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Evolutionär organismbiologi.
    Snitting, Daniel
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Evolutionär organismbiologi.
    The virtual Eusthenopteron: inside the head of a Devonian lobe-fin with CT. In A. Ivanov and G. Young (eds.), Middle Palaeozoic Vertebrates from Laurussia: Relationships with Siberia, Kazakhstan, Asia and Gondwana. Ichthyolith Issues Special Publication 9:3–4.2005Annet (Annet vitenskapelig)
  • 4.
    Ahlberg, Per E.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Evolutionär organismbiologi.
    Clack, Jennifer A.
    Palaeontology: A firm step from water to land2006Inngår i: Nature, ISSN 0028-0836, Vol. 440, nr 7085, 747-749 s.Artikkel i tidsskrift (Fagfellevurdert)
  • 5.
    Ahlberg, Per Erik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Humeral homology and the origin of the tetrapod elbow: a reinterpretation of the enigmatic specimens ANSP 21350 and GSM 1045362011Inngår i: Studies on fossil tetrapods / [ed] P. M. Barrett, A. R. Milner, London: The Palaeontological Association , 2011, 17-29 s.Kapittel i bok, del av antologi (Fagfellevurdert)
    Abstract [en]

    Two putative tetrapod humeri of Devonian age, ANSP 21350 from the late Famennian of Pennsylvania and GSM 104536 from the late Frasnian of Scat Craig, Scotland, are reinterpreted in the light of more recent discoveries. The morphology of ANSP 21350 can be more fully homologized with those of elpistostegids and early tetrapods than previously recognized. Unique features include distally displaced dorsal muscle attachments and a ventrally rotated distal face of the bone. This suggests that a weight-bearing ventrally directed forearm was created, not by means of a flexed elbow as in other tetrapods, but by distorting the humerus. The olecranon process on the ulna was probably poorly developed or absent. Primitive characters that are absent in other tetrapods add support to the contention that ANSP 21350 is the least crownward of known tetrapod humeri. Contrary to previous claims, Acanthostega has a characteristic tetrapod ulnar morphology with an olecranon process; it does not resemble an elpistostegid ulna and is not uniquely primitive for tetrapods. This suggests that the flexed tetrapod elbow with ulnar extensor muscles attached to the olecranon evolved simultaneously with the large rectangular entepicondyle typical for early tetrapods, probably as part of a single functional complex. GSM 104536 is denfinitely not a primitive tetrapod humerus, nor a sarcopterygian branchial bone, but cannot be positively identified at present.    

  • 6.
    Al- Robeyi, Zainab
    Karlstads universitet, Fakulteten för samhälls- och livsvetenskaper.
    Att uppleva naturen med alla sina sinnen: Hur undersöker och upplever förskolebarnen naturen?2013Independent thesis Basic level (university diploma), 10 poäng / 15 hpOppgave
    Abstract [en]

    Abstract

    This project discusses various aspects of children's way to explore nature with their senses. Therefore I conducted a study in two preschools, one nature-oriented and another preschool. This study was carriedout usien the three metods, interviews, observations and surveys. Interview four children from each preschool, observations of each group outdoors during four different occasions and question forms to teachers.

     

    The result of the study showed that both teachers and children have a great interest in being outdoors in nature, but it is not always possible to take out all children's groups. The reason is large groups and inadequate staff. When you are out in the forest according to teachers, it is important to be attentive, present, and meet the children’s interests. They need to be stimulated with questions and inspire them about what is happening and what might happen in nature plus take natural materials as help in the creative activities of the preschool.

     

    Keywords: Biology, children's perceptions, exploring, outdoor environment

  • 7.
    Ali, Fuad
    Södertörns högskola, Institutionen för livsvetenskaper.
    Developing electroporation as a method to obtain Stable Transformation in Drosophila melanogaster2008Independent thesis Advanced level (degree of Master (Two Years)), 20 poäng / 30 hpOppgave
    Abstract [en]

    In this project I have tried to obtain stable transformants of Drosophila melanogaster flies using electroporation. I have completed approximately 200 tests using different DNA concentrations, voltages and cuvettes, including a novel Petri dish cuvette which I developed and manufactured myself. I also developed new and more efficient procedures of egg collection and egg dechorionation. Although I was not  successful in obtaining true stable transformants, control experiments indicate that electroporation of DNA into embryos could be accomplished under the conditions used. The lack of stable transformants was probably due to failure of the electroporated DNA to integrate into the host genome. The reasons for why the DNA did not integrate was not further investigated in this study.

  • 8.
    Allan, Douglas W
    et al.
    Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115 USA.
    St Pierre, Susan E
    Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115 USA.
    Miguel-Aliaga, Irene
    Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115 USA.
    Thor, Stefan
    Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115 USA.
    Specification of Neuropeptide Cell Identity by the Integration of Retrograde BMP Signaling and a Combinatorial Transcription Factor Code2003Inngår i: Cell, ISSN 0092-8674, E-ISSN 1097-4172, Vol. 113, nr 1, 73-86 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Individual neurons express only one or a few of the many identified neurotransmitters and neuropeptides, but the molecular mechanisms controlling their selection are poorly understood. In the Drosophila ventral nerve cord, the six Tv neurons express the neuropeptide gene FMRFamide. Each Tv neuron resides within a neuronal cell group specified by the LIM-homeodomain gene apterous. We find that the zinc-finger gene squeeze acts in Tv cells to promote their unique axon pathfinding to a peripheral target. There, the BMP ligand Glass bottom boat activates the Wishful thinking receptor, initiating a retrograde BMP signal in the Tv neuron. This signal acts together with apterous and squeeze to activate FMRFamide expression. Reconstituting this "code," by combined BMP activation and apterous/squeeze misexpression, triggers ectopic FMRFamide expression in peptidergic neurons. Thus, an intrinsic transcription factor code integrates with an extrinsic retrograde signal to select a specific neuropeptide identity within peptidergic cells.

  • 9. Allendorf, Fred
    et al.
    Ryman, Nils
    Stockholms universitet, Naturvetenskapliga fakulteten, Zoologiska institutionen.
    The role of genetics in population viability analysis2002Inngår i: Population Viability Analysis / [ed] Beissinger,S.R. and McCullough,D.R., Chicago: University of Chicago Press , 2002, 50-85 s.Kapittel i bok, del av antologi (Annet vitenskapelig)
  • 10.
    Alsmark, Cecilia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för evolutionsbiologi, Molekylär evolution.
    Comparative Genomics of Obligate and Facultative Intracellular Parasites2002Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The α-proteobacteria Rickettsia prowazekii and Bartonella henselae are the causative agents of epidemic typhus and cat scratch disease respectively. Whereas R. prowazekii is an obligate intracellular parasite, B. henselae can live and proliferate both outside and inside the eukaryotic host cell. Besides the obvious medical interest to identify the complete gene set of two human pathogens, their genome sequences are also important for the study of evolutionary processes. Both R. prowazekii and B. henselae have small genomes, but their last common ancestor of these two bacteria was most likely a free-living organism with a substantially larger genome.

    The aim of this thesis is to compare the complete genomes of R. prowazekii and B. henselae and to decipher the evolutionary processes leading to the adaptation to an intracellular lifestyle. The working hypothesis was that the facultative intracellular B. henselae is an intermediate between a free living bacteria and the obligate R. prowazekii, which is corroborated. B. henselae has a broader biosynthetic repertoire than R. prowazekii, including the presence of genes for glycolysis and de novo biosynthesis of purines and pyrimidines. However, both bacteria have reduced gene sets for biosynthesis of amino acids and cofactors compared to free-living bacteria.

    Comparisons of gene order in bacteria reveal that several operons are well conserved between distantly related species. The genome sequences of R. prowazekii and B. henselae show that many of the operons that are usually conserved, are broken and rearranged in these species. One of the mechanisms of reductive evolution include intra-chromosomal recombination between repeated loci. This process expels one of the repeats and cause rearrangements in the gene order of the flanking regions. While the R. prowazekii genome almost completely lack repeated sequences, the B. henselae genome is rich in repeats. These repeats are, however, most often located within regions associated with pathogenicity islands. The higher number of scrambled operons, and the lower number of repeats, in R. prowazekii compared to B. henselae imply that the reductive process has gone further in the former species.

  • 11.
    Alvarez-Rodriguez, Manuel
    University of Leon, Facultad de Ciencias Biologicas y Ambientales, Spain.
    Mejora y evolución de los protocolos de congelación de eyaculados de oso pardo (Ursus arctos)2012Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [es]

    La situación crítica del oso pardo (Ursus arctos) en España plantea la necesidad de aplicar diferentes estrategias de conservación, dentro de las cuales tiene especial relevancia la creación de un banco de recursos genéticos. La eficacia de esta herramienta depende, entre otros factores, de la adaptación específica de los protocolos de congelación espermática ya existentes y que permitan el almacenamiento eficaz de los espermatozoides del oso pardo en un banco de germoplasma. Este trabajo nos permite concluir la utilidad de la selección entre ciclos con el fin de mejorar la calidad de los espermatozoides sometidos a recongelación

  • 12.
    Alvarez-Rodriguez, Manuel
    et al.
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    Alvarez, Mercedes
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    Gomes-Alves, S
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    Borragan, Santiago
    Cabárceno Park, Cantabria, Spain.
    Martinez-Pastor, Felipe
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Molecular Biology (Cell Biology), University of León, León, Spain.
    de Paz, Paulino
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Molecular Biology (Cell Biology), University of León, León, Spain.
    Anel, Luis
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    Quality of frozen-thawed semen in brown bear is not affected by timing of glycerol addition.2011Inngår i: Theriogenology, ISSN 0093-691X, E-ISSN 1879-3231, Vol. 75, nr 8, 1561-1565 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We have tested several freezing protocols for brown bear semen, modifying the time when glycerol was added (before and after cooling to 5 °C). No differences were found among protocols, indicating a good tolerance of brown bear semen to glycerol. This finding indicates that freezing protocols for brown bear semen could be modified to fit practical solutions which would facilitate preparation of the seminal samples in the field with the addition of glycerol at ambient temperature.

  • 13.
    Alvarez-Rodríguez, Manuel
    et al.
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    Alvarez, Mercedes
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    Anel-López, Luis
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    Martínez-Rodríguez, Carmen
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Molecular Biology (Cell Biology), University of León, Campus de Vegazana, León Spain.
    Martínez-Pastor, Felipe
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Molecular Biology (Cell Biology), University of León, Campus de Vegazana, León Spain.
    Borragan, Santiago
    Cabárceno Park, Cantabria, Spain.
    Anel, Luis
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    de Paz, Paulino
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Molecular Biology (Cell Biology), University of León, Campus de Vegazana, León Spain.
    The antioxidant effects of soybean lecithin- or low-density lipoprotein-based extenders for the cryopreservation of brown-bear (Ursus arctos) spermatozoa.2013Inngår i: Reproduction, Fertility and Development, ISSN 1031-3613, E-ISSN 1448-5990, Vol. 25, nr 8, 1185-1193 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Egg yolk low-density lipoproteins (LDL) and soybean lecithin were evaluated as replacements for egg yolk in extenders used for the cryopreservation of brown-bear spermatozoa. The motility, viability and acrosomal status of post-thawed spermatozoa were analysed, and an egg-yolk extender was used as a control. The total antioxidant capacity of these extenders was tested. Soybean lecithin showed an effect that was dependent on the soybean concentration (2%, 3.5% and 5%) and source (Type A: 24% L-α-phosphatidylcholine, and Type B: 14-23% L-α-phosphatidylcholine). Only semen cryopreserved with 5% Type A soybean exhibited a sperm motility similar to that of semen cryopreserved in egg-yolk-based extender after thawing, although the sperm viability and acrosome status were not as high. Semen frozen in an extender containing LDL (10-15%) exhibited improved sperm viability in comparison with the control, but sperm motility was lower. The LDL-based extender exhibited a higher anti-oxidant activity than the egg-yolk extender and soy lecithin-based extenders. The extenders with higher anti-oxidant activity showed improvements in frozen sperm viability but lower semen motility. These results indicate that soybean lecithin did not have the same protective effect as egg yolk during the freezing of brown-bear spermatozoa but suggest that LDL (10-15%) could be a useful substitute for egg yolk in these extenders.

  • 14.
    Alvarez-Rodríguez, Manuel
    et al.
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain .
    Alvarez, Mercedes
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    Borragan, Santiago
    Cabárceno Park, Cantabria, Spain.
    Martinez-Pastor, Felipe
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Molecular Biology (Cell Biology), University of León, León, Spain .
    Holt, W V
    The Academic Unit of Reproductive and Developmental Medicine, University of Sheffield, Sheffield, UK.
    Fazeli, Alireza
    The Academic Unit of Reproductive and Developmental Medicine, University of Sheffield, Sheffield, UK.
    de Paz, Paulino
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Molecular Biology (Cell Biology), University of León, León, Spain .
    Anel, Luis
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    The addition of heat shock protein HSPA8 to cryoprotective media improves the survival of brown bear (Ursus arctos) spermatozoa during chilling and after cryopreservation.2013Inngår i: Theriogenology, ISSN 0093-691X, E-ISSN 1879-3231, Vol. 79, nr 3, 541-550 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The Cantabrian brown bear survives as a small remnant population in northern Spain and semen cryopreservation for future artificial insemination is one of the measures being implemented for conservation of this species. As part of this program we investigated the value of adding heat shock protein A8 (HSPA8) to media (N-[Tris(hydroxymethyl)methyl]-2-aminoethanesulfonic acid-TRIS-fructose with 20% egg yolk) used for chilling and cryopreserving the spermatozoa. Semen samples from eight brown bears were obtained by electroejaculation during the breeding season. In experiment 1, we tested three concentrations of HSPA8 (0.5, 1, and 5 μg/mL) to determine whether sperm motility (computer assisted sperm analysis system) and sperm survival could be improved during refrigeration (5 °C) up to 48 hours. Results showed that sperm viability (test with propidium iodide) was improved by the addition of 0.5 and 5 μg/mL HSPA8. In experiment 2, HSPA8 was added to the cryopreservation media (6% final glycerol concentration) before the freezing process. Though there were no differences in sperm viability immediately after thawing (analyses to 0 hours), plasma membrane permeability (test with YO-PRO-1) was significantly lower by the presence of HSPA8 (1 μg/mL) and acrosomal damage (test with peanut agglutinin-fluorescein isothiocyanate conjugate) was reduced by higher concentrations of HSPA8 (1 and 5 μg/mL) (analyses after thermal stress test incubating over 2 hours to 37 °C). In experiment 3, results of a simple progression test carried out through artificial mucus (hyaluronic acid 4 mg/mL) showed a significant decrease in the total number of sperm able to swim a distance of 0.5 to 2 cm through a capillary tube for all HSPA8-based extenders. Nevertheless, the distance traveled by the vanguard spermatozoa, which represent a highly motile subpopulation, was restored by the inclusion of 1 and 5 μg/mL HSPA8 in the cryopreservation media. Thus, the HSPA8 addition to extender improves the quality of brown bear (Ursus arctos) sperm during chilling (viability) and after cryopreservation (number of sperm with damaged acrosomes and "apoptotic-like" changes).

  • 15.
    Alvarez-Rodríguez, Manuel
    et al.
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    Alvarez, Mercedes
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    López-Urueña, Elena
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    Martínez-Rodriguez, Carmen
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Molecular Biology (Cell Biology), University of León, León, Spain.
    Borragan, Santiago
    Cabárceno Park, Cabárceno, Cantabria, Spain.
    Anel-López, Luis
    SaBio IREC (CSIC-UCLM-JCCM), Albacete, Spain.
    de Paz, Paulino
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Molecular Biology (Cell Biology), University of León, León, Spain.
    Anel, Luis
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    Brown bear sperm double freezing: Effect of elapsed time and use of PureSperm(®) gradient between freeze-thaw cycles.2013Inngår i: Cryobiology, ISSN 0011-2240, E-ISSN 1090-2392, Vol. 67, nr 3, 339-346 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The use of sexed spermatozoa has great potential to captive population management in endangered wildlife. The problem is that the sex-sorting facility is a long distance from the semen collection place and to overcome this difficulty two freeze-thaw cycles may be necessary. In this study, effects of refreezing on brown bear electroejaculated spermatozoa were analyzed. We carried out two experiments: (1) to assess the effects of the two freezing-thawing cycles on sperm quality and to analyze three different elapsed times between freezing-thawing cycles (30, 90 and 180 min), and (2) to analyze the use of PureSperm between freezing-thawing cycles to select a more motile and viable sperm subpopulation which better survived first freezing. The motility, viability and undamaged acrosomes were significantly reduced after the second thawing respect to first thawing into each elapsed time group, but the elapsed times did not significantly affect the viability and acrosome status although motility was damaged. Our results with the PureSperm gradient showed higher values of viability in freezability of select sample (pellet) respect to the rest of the groups and it also showed a significant decrease in the number of acrosome damaged. In summary, the double freezing of bear semen selected by gradient centrifugation is qualitatively efficient, and thus could be useful to carry out a sex-sorting of frozen-thawed bear spermatozoa before to send the cryopreserved sample to a biobank. Given the low recovery of spermatozoa after applying a selection gradient, further studies will be needed to increase the recovery rate without damaging of the cell quality.

  • 16.
    Amiri, Haleh
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för evolutionsbiologi, Molekylär evolution.
    Patterns and Processes of Molecular Evolution in Rickettsia2002Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Species of the genus Rickettsia are obligate intracellular parasites of the a-proteobacterial subdivision. It has been suggested that obligate intracellular bacteria have evolved from free-living bacteria with much larger genome sizes. Transitions to intracellular growth habitats are normally associated with radical genomic alterations, particularly genome rearrangements and gene losses.

    This thesis presents a comparative study of evolutionary processes such as gene rearrangements, deletions and duplications in a variety of Rickettsia species. The results show that early intrachromosomal recombination events mediated by duplicated genes and short repeats have resulted in deletions as well as rearrangements. For example, an exceptional organization of the elongation factor genes was found in all species examined, suggesting that this rearrangement event occurred at the early stage of the evolution of Rickettsia. Likewise, it was found that a repetitive element, the so-called Rickettsia Palindromic Element (RPE) flourished prior to species divergence in Rickettsia. Finally, a phylogenetic analysis shows that the duplication events that gave rise to the five genes encoding ATP/ADP transporters occurred long before the divergence of the two major groups of Rickettsia. Taken together, this suggests that Rickettsia have been intracellular parasites for an extensive period of time.

    A detailed analysis of the patterns of nucleotide changes in genes and intergenic regions among the different species provides evidence for a gradual accumulation of short deletions. This suggests that different distributions of genes and repeated sequences in modern Rickettsia species reflect species-specific differences in rates of deterioration rather than variation in rates of intra-genomic sequence proliferation.

  • 17.
    Andersson, Hans Ola
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för evolutionsbiologi.
    Structure-aided design of antiviral drugs: Application of the method on HIV-1 protease and SIV reverse transcriptase1999Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Many efforts have been made to control the AIDS epidemic. Extensive studies have been done on the biology, biochemistry, and structural biology of HIV in the search for antiviral drugs. The viral-encoded enzymes reverse transcriptase and protease have been main targets for drug design.

    Our study on the HIV-1 protease involves the X-ray structure determination of ten complexes with C-terminally duplicated linear inhibitors and two complexes with C2-symmetric cyclic inhibitors. The structural study of the HIV-1 protease/linear inhibitors revealed several interesting properties of the protease, such as the flexibility of S2/S2' subsites, and the presence of coupled and symmetry restricted adaptation of the inhibitor binding subsites. We also found that the inhibitors adopted specific asymmetric conformation of their central parts, where only one of the gemdiol-hydroxyls is pointing toward the catalytic aspartates. The study of the C2-symmetric cyclic inhibitors showed that despite our efforts to promote a symmetric binding of the sulfamide compound, it seems prone to bind non-symmetrically. Our research has resulted in several highly competent inhibitor compounds.

    The work on sooty mangabey SIV reverse transcriptase (SIVsm RT) involves the expression,purification, characterization and studies of inhibition. A simple and efficient large-scalepreparation method was developed for SIVsm RT, in which processing of the p65/p65homodimer to the p65/p51 heterodimer was done with HIV-1 protease. The catalyticproperties of SIVsm RT were characterized. The sensitivity toward non-nucleoside inhibitorsNNI's) of SIVsm RT was distinct from HIV-1. By screening an inhibitor-library, two leadcompounds, MSK-046 and MSK-076 (IC50-values of ~10 µ), belonging to the PETT-serieswere identified.

  • 18.
    Andersson, Jan O.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för evolutionsbiologi.
    Molecular evolutionary studies of genome degradation in bacteria1999Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The genus Rickettsia belongs to the α-proteobacteria and consists of obligate intracellular bacteria, which often are pathogenic for humans. All Rickettsia have small genomes, highly adapted to an intracellular lifestyle. However, the ancestors of Rickettsia were most likely free-living organisms with substantially larger genomes, This thesis is a study of the reductive evolutionary processes by which Rickettsia has adapted to a life inside eukaryotic cells.

    The Rickettsia prowazekii genome sequence confirmed the close phylogenetic relationship between the genus Rickettsia and the mitochondria. In addition, 12 putative pseudogenes and an unusually large fraction of non-coding DNA (24%) were identified. Analysis of the metK genomic region in different Rickettsia species identified metK as a pseudogene in all but two lineages. The pattern of mutations indicated that the pseudogenes are no longer under purfying selection, and that metK was inactivated several times independently in different lineages. Similar patterns were found in many other Rickettsia pseudogenes, revealing an ongoing genome degradation process in the Rickettsia.

    Analysis of neutrally evolving pseudogenes showed that deletions dominate over insertions, and that there is a mutational bias towards A+T nucleotides, in the Rickettsia genomes. In agreement, the long intergenic regions in the R. prowazekii genome have a decreased G+C content. Several of these regions showed sequence homology to genes in orthologous positions in other Rickettsia genomes, which indicated that the long intergenic regions represent old genes that are disappearing from the genome.

    The ancestor of the two major Rickettsia groups may have encoded 200-300 additional genes compared to R. prowazekii. Differential loss of mostly genus specific genes during the evolution resulted in the present-day Rickettsia genomes. Currently, Rickettsia inactivates genes at a higher than they are eliminated from the genome by fixation of deletions.

  • 19.
    Andersson, Marie
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Cellular transport and secretion of the cyanobacterial neurotoxin BMAA into milk and egg: Implications for developmental neurotoxicity2015Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The cyanobacterial amino acid β-N-methylamino-L-alanine (BMAA) is a neurotoxin implicated in the etiology of neurodegenerative diseases. Cyanobacteria are cosmopolitan organisms present in various environments. BMAA can cause long-term neurodegenerative alterations in rats exposed during the neonatal period, a period that corresponds to the last trimester and the first few years of life in humans. As BMAA has been reported to be bioaccumulated in the aquatic food chain and detected in mussels, crayfish and fish used for human consumption, the main aim of this thesis has been to investigate the final step in the mammalian food-chain, i.e. the transfer of BMAA into breast milk.

    Autoradiographic imaging and mass spectrometry analysis showed an enantiomer-selective uptake of BMAA and that the neurotoxin was transferred from lactating mice and rat, via the milk, to the brain of the nursed pups. The results show that transport of BMAA may be disproportional to dose. In addition, BMAA was found present both as free amino acid and tightly associated to proteins in rat brains. Surprisingly, however, no association to milk proteins was found. In vitro studies of murine (HC11) and human (MCF7) mammary epithelial cells suggest that BMAA can pass the human mammary epithelium into milk. Additional transport studies on human intestinal, glioblastoma and neuroblastoma cells showed that L-BMAA was consistently favored over D-BMAA and that the transport was mediated by several amino acid transporters. We also demonstrated that egg-laying quail transfer BMAA to its offspring by deposition in the eggs, particularly in the yolk but also in the albumen. Furthermore, comparative analysis of carboxyl- and methyl-labeled [14C]-BMAA suggested that BMAA was not metabolized to a large degree.

    Altogether, the results indicate that BMAA can be transferred from mothers, via the milk, to the brain of nursed human infants. Determinations of BMAA in mothers’ milk and cows’ milk are therefore warranted. We also propose that birds’ eggs could be an additional source of BMAA exposure in humans. It might therefore be of concern that mussels are increasingly used as feed in commercial egg production.

  • 20.
    Andersson, Marie
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Ersson, Lisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Brandt, Ingvar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Bergström, Ulrika
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Potential transfer of neurotoxic amino acid beta-N-methylamino-L-alanine (BMAA) from mother to infant during breast-feeding: Predictions from human cell lines2017Inngår i: Toxicology and Applied Pharmacology, ISSN 0041-008X, E-ISSN 1096-0333, Vol. 320, 40-50 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    β-N-methylamino-alanine (BMAA) is a non-protein amino acid produced by cyanobacteria, diatoms and dinoflagellates. BMAA has potential to biomagnify in a terrestrial food chain, and to bioaccumulate in fish and shellfish. We have reported that administration of [14C]l-BMAA to lactating mice and rats results in a mother to off-spring transfer via the milk. A preferential enantiomer-specific uptake of [14C]l-BMAA has also been demonstrated in differentiated murine mammary epithelium HC11 cells. These findings, together with neurotoxic effects of BMAA demonstrated both in vitro and in vivo, highlight the need to determine whether such transfer could also occur in humans. Here, we used four cell lines of human origin to examine and compare the transport of the two BMAA enantiomers in vitro. The uptake patterns of [14C]l- and [14C]d-BMAA in the human mammary MCF7 cell line were in agreement with the results in murine HC11 cells, suggesting a potential secretion of BMAA into human breast milk. The permeability coefficients for both [14C]l- and [14C]d-BMAA over monolayers of human intestinal Caco2 cells supported an efficient absorption from the human intestine. As a final step, transport experiments confirmed that [14C]l-and [14C]d-BMAA can be taken up by human SHSY5Y neuroblastoma cells and even more efficiently by human U343 glioblastoma cells. In competition experiments with various amino acids, the ASCT2 specific inhibitor benzylserine was the most effective inhibitor of [14C]l-BMAA uptake tested here. Altogether, our results suggest that BMAA can be transferred from an exposed mother, via the milk, to the brain of the nursed infant.

  • 21.
    Andersson, Marie
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Karlsson, Oskar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap. Karolinska Inst, Dept Clin Neurosci, Ctr Mol Med, SE-17176 Stockholm, Sweden.
    Banack, Sandra
    Inst Ethnomed, POB 3464, Jackson, WY 83001 USA.
    Brandt, Ingvar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Transfer of developmental neurotoxin beta-N-methylamino-L-alanine (BMAA) via milk to nursed offspring: Studies by mass spectrometry and image analysis2016Inngår i: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 258, 108-114 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The cyanobacterial non-proteinogenic amino acid beta-N-methylamino-L-alanine (BMAA) is proposed to be involved in the etiology of amyotrophic lateral sclerosis/parkinsonism dementia complex. When administered as single doses to neonatal rats, BMAA gives rise to cognitive and neurodegenerative impairments in the adult animal. Here, we employed mass spectrometry (LC-MS/MS) and autoradiographic imaging to examine the mother-to-pup transfer of BMAA in rats. The results show that unchanged BMAA was secreted into the milk and distributed to the suckling pups. The concentration of BMAA in pup stomach milk and the neonatal liver peaked after 8 h, while the concentration in the pup brain increased throughout the study period. About 1 and 6% of the BMAA recovered from adult liver and brain were released following hydrolysis, suggesting that this fraction was associated with protein. No association to milk protein was observed. Injection of rat pups with [methyl-C-14]-L-BMAA or [carboxyl-C-14]-L-BMAA resulted in highly similar distribution patterns, indicating no or low metabolic elimination of the methylamino- or carboxyl groups. In conclusion, BMAA is transported as a free amino acid to rat milk and suckling pups. The results strengthen the proposal that mothers' milk could be a source of exposure for BMAA in human infants. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

  • 22.
    Andersson, Marie
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Karlsson, Oskar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Bergström, Ulrika
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Brittebo, Eva B.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Brandt, Ingvar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Correction: Maternal Transfer of the Cyanobacterial Neurotoxin β-N-Methylamino-L-Alanine (BMAA) via Milk to Suckling Offspring2015Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 10, e78133Artikkel i tidsskrift (Fagfellevurdert)
  • 23.
    Andersson, Marie
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Karlsson, Oskar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Brandt, Ingvar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Deposition of cyanobacterial neurotoxin beta-N-methylamino-L-alanine (L-BMAA) in birds' egg: A potential source of BMAA exposure in humansManuskript (preprint) (Annet vitenskapelig)
  • 24.
    Andersson, Måns S.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för evolutionsbiologi.
    Physiological trade-offs in reproduction and condition dependence of a secondary sexual trait2001Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    This thesis examines parental condition, how it is traded off against reproduction and how it is displayed in a secondary sexual trait. The studies were performed on nest-box breeding collared flycatchers Ficedula albicollis on the island of Gotland, in the Baltic Sea. Early breeding and high fitness were found to be associated with high levels of glycosylated haemoglobin possibly governed by migratory exertion and infectious disease. In order to test if immune function is expressed in secondary sexual traits and how it is traded off against reproductive effort a series of experiments were performed, in which birds were challenged with an antigen, via a vaccine containing neutralised paramyxovirus. The forehead patch of the male collared flycatcher serves as a badge of status and is under sexual selection. Good condition, as reflected in strong immune response and low levels of blood parasites was found to be associated with bigger patch size. Patch size was also found to vary in size within the same breeding season in a pattern predictable from immune response data. Immune response, in itself, was found to be costly in terms of reduced survival, confirming that trade-offs involving suppression of immune response may increase fitness. Mating effort was found to be traded off against immune function and moult. Experimental brood size manipulations revealed a trade-off females between number of offspring and immune function. Thus I suggest a set of parameters useful for condition estimation. I also show that immune response is costly and, second, that pathogen resistance probably plays an important role in the shaping of secondary sexual traits and life-history decisions.

  • 25.
    Andrae, Johanna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Vaskulärbiologi.
    Betsholtz, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Vaskulärbiologi.
    Gouveia, Maria Leonor Seguardo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Vaskulärbiologi.
    PDGFR alpha signaling is required for alveolar development in the mouse lung2017Inngår i: Mechanisms of Development, ISSN 0925-4773, E-ISSN 1872-6356, Vol. 145, S147-S147 s.Artikkel i tidsskrift (Annet vitenskapelig)
  • 26. Andreae, Laura C
    et al.
    Peukert, Daniela
    Lumsden, Andrew
    Gilthorpe, Jonathan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Analysis of Lrrn1 expression and its relationship to neuromeric boundaries during chick neural development2007Inngår i: Neural Development, ISSN 1749-8104, Vol. 2, nr 22, 1-16 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: The Drosophila leucine-rich repeat proteins Tartan (TRN) and Capricious (CAPS) mediate cell affinity differences during compartition of the wing imaginal disc. This study aims to identify and characterize the expression of a chick orthologue of TRN/CAPS and examine its potential function in relation to compartment boundaries in the vertebrate central nervous system.

    RESULTS: We identified a complementary DNA clone encoding Leucine-rich repeat neuronal 1 (Lrrn1), a single-pass transmembrane protein with 12 extracellular leucine-rich repeats most closely related to TRN/CAPS. Lrrn1 is dynamically expressed during chick development, being initially localized to the neural plate and tube, where it is restricted to the ventricular layer. It becomes downregulated in boundaries following their formation. In the mid-diencephalon, Lrrn1 expression prefigures the position of the anterior boundary of the zona limitans intrathalamica (ZLI). It becomes progressively downregulated from the presumptive ZLI just before the onset of expression of the signalling molecule Sonic hedgehog (Shh) within the ZLI. In the hindbrain, downregulation at rhombomere boundaries correlates with the emergence of specialized boundary cell populations, in which it is subsequently reactivated. Immunocolocalization studies confirm that Lrrn1 protein is endocytosed from the plasma membrane and is a component of the endosomal system, being concentrated within the early endosomal compartment.

    CONCLUSION: Chick Lrrn1 is expressed in ventricular layer neuroepithelial cells and is downregulated at boundary regions, where neurogenesis is known to be delayed, or inhibited. The timing of Lrrn1 downregulation correlates closely with the activation of signaling molecule expression at these boundaries. This expression is consistent with the emergence of secondary organizer properties at boundaries and its endosomal localisation suggests that Lrrn1 may regulate the subcellular localisation of specific components of signalling or cell-cell recognition pathways in neuroepithelial cells.

  • 27. Andriamihajarivo, Tefy H.
    et al.
    Razafimandimbison, Sylvain G.
    Stockholms universitet, Naturvetenskapliga fakulteten, Botaniska institutionen.
    Karehed, Jesper
    Phyllopentas flava (Rubiaceae), a New Morphologically Heterodistylous and Functionally Dioecious Species from Madagascar2011Inngår i: Systematic Botany, ISSN 0363-6445, E-ISSN 1548-2324, Vol. 36, nr 4, 1024-1027 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A new species of the Afro-Malagasy genus Phyllopentas Karehed & B. Bremer, Phyllopentas flava Razafim., T. Andriam. et Karehed, is described and illustrated. This plant is restricted to the Itremo region in southeastern Madagascar and is distinct morphologically from the other species of the genus by its pubescent, narrowly ovate to narrowly elliptic leaves, grey-whitish and thickly hairy midribs and secondary veins on the lower surfaces of leaves, and functionally dioecious and heterodistylous flowers. Summaries of distribution, phenology, habitat, and ecology are given and a conservation assessment is also provided.

  • 28. André, Carl
    et al.
    Larsson, Lena C
    Stockholms universitet, Naturvetenskapliga fakulteten, Zoologiska institutionen.
    Laikre, Linda
    Stockholms universitet, Naturvetenskapliga fakulteten, Zoologiska institutionen.
    Bekkevold, D
    Brigham, J
    Carvalho, GR
    Dahlgren, TG
    Hutchinson, WF
    Mariani, S
    Mudde, K
    Ruzzante, DE
    Ryman, Nils
    Stockholms universitet, Naturvetenskapliga fakulteten, Zoologiska institutionen.
    Detecting population structure in a high gene-flow species, Atlantic herring (Clupea harengus): direct, simultaneous evaluation of neutral vs putatively selected loci2011Inngår i: Heredity, ISSN 0018-067X, E-ISSN 1365-2540, Vol. 106, nr 2, 270-280 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In many marine fish species, genetic population structure is typically weak because populations are large, evolutionarily young and have a high potential for gene flow. We tested whether genetic markers influenced by natural selection are more efficient than the presumed neutral genetic markers to detect population structure in Atlantic herring (Clupea harengus), a migratory pelagic species with large effective population sizes. We compared the spatial and temporal patterns of divergence and statistical power of three traditional genetic marker types, microsatellites, allozymes and mitochondrial DNA, with one microsatellite locus, Cpa112, previously shown to be influenced by divergent selection associated with salinity, and one locus located in the major histocompatibility complex class IIA (MHC-IIA) gene, using the same individuals across analyses. Samples were collected in 2002 and 2003 at two locations in the North Sea, one location in the Skagerrak and one location in the low-saline Baltic Sea. Levels of divergence for putatively neutral markers were generally low, with the exception of single outlier locus/sample combinations; microsatellites were the most statistically powerful markers under neutral expectations. We found no evidence of selection acting on the MHC locus. Cpa112, however, was highly divergent in the Baltic samples. Simulations addressing the statistical power for detecting population divergence showed that when using Cpa112 alone, compared with using eight presumed neutral microsatellite loci, sample sizes could be reduced by up to a tenth while still retaining high statistical power. Our results show that the loci influenced by selection can serve as powerful markers for detecting population structure in high gene-flow marine fish species.

  • 29.
    Anel-López, Luis
    et al.
    Biology of Reproduction Group. National Wildlife Research Institute (IREC) (UCLM-CSIC-JCCM), Albacete, Spain.
    Alvarez-Rodríguez, Manuel
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    García-Álvarez, Olga
    Biology of Reproduction Group. National Wildlife Research Institute (IREC) (UCLM-CSIC-JCCM), Albacete, Spain.
    Alvarez, Mercedes
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    Maroto-Morales, Alejandro
    Biology of Reproduction Group. National Wildlife Research Institute (IREC) (UCLM-CSIC-JCCM), Albacete, Spain.
    Anel, Luis
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Animal Reproduction and Obstetrics, University of León, León, Spain.
    de Paz, Paulino
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Molecular Biology (Cell Biology), University of León, León, Spain.
    Garde, J Julián
    Biology of Reproduction Group. National Wildlife Research Institute (IREC) (UCLM-CSIC-JCCM), Albacete, Spain.
    Martínez-Pastor, Felipe
    ITRA-ULE, INDEGSAL, University of León, León, Spain; Molecular Biology (Cell Biology), University of León, León, Spain.
    Reduced glutathione and Trolox (vitamin E) as extender supplements in cryopreservation of red deer epididymal spermatozoa2012Inngår i: Animal Reproduction Science, ISSN 0378-4320, E-ISSN 1873-2232, Vol. 135, nr 1-4, 37-46 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The use of assisted reproductive techniques in cervids is increasing as the commercial use of these species increase. We have tested the suitability of the antioxidants Trolox and reduced glutathione (GSH) for freezing red deer epididymal spermatozoa, aiming at improving post-thawing quality. Samples from 19 stags were frozen in a TES-Tris-fructose extender (20% egg yolk, 8% glycerol), with 1 or 5 mM of antioxidant. Motility (CASA), lipoperoxidation (malondialdehyde -MDA- production), membrane status, mitochondrial activity, acrosomal status (flow cytometry) and chromatin status (SCSA: %DFI and %HDS; flow cytometry) were assessed after thawing and after 6 h at 39°C. There were few differences between treatments after thawing, with Trolox reducing MDA production in a dose-response manner. After the incubation, sperm quality decreased and %DFI increased moderately, with no change for MDA. GSH improved motility, kinematic parameters and mitochondrial status, with a slight increase in %HDS. GSH 5 mM also increased moderately MDA production and %DFI, possibly due to enhanced metabolic activity and reducing power. Trolox maintained MDA low, but was detrimental to sperm quality. Trolox might not be appropriate for the cryopreservation of red deer epididymal spermatozoa, at least at the millimolar range. GSH results are promising, especially regarding motility improvement after the post-thawing incubation, and should be selected for future fertility trials.

  • 30.
    Archer, Amena
    et al.
    Karolinska Institutet.
    Kitambi, Satish Srinivas
    Karolinska Institutet.
    Hallgren, Stefan
    Södertörns Universitet.
    Pedrelli, Mateo
    Karolinska Institutet.
    Olsén, Håkan
    Södertörns Högskola.
    Agneta, Mode
    Karolinska Institutet.
    Gustafsson, Jan-Åke
    Karolinska Institutet.
    The liver X receptor (lxr) governs lipid homeostasis in zebrafish during development2012Inngår i: Open Journal of Endocrine and Metabolic Diseases, ISSN 2165-7432, Vol. 2, 74-81 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The liver X-receptors (LXRs) act as cholesterol sensors and participate in the regulation of lipid and cholesterol metabolism. The objective of this study was to determine the role of LXR during development using the zebrafish model. By in situ hybridization we showed distinct expression of lxr in the brain and the retina in the developing and adult zebrafish. Lxr ligand activation affected the expression of genes involved in lipid metabolism in zebrafish adult brain and eye as well as in zebrafish embryos. Morpholino knock down of lxr resulted in an overall impaired lipid deposition as determined by oil red O staining particularly in the head and around the eyes, and to significantly elevated levels of both total and free cholesterol in the yolk of lxr morphant embryos. The expression of genes involved in lipid and cholesterol metabolism was also changed in the lxr morphants. Furthermore, alcian blue staining revealed malformation of the pharyngeal skeleton in the lxr morphant. Our data show that lxr is an important component of the regulatory network governing the lipid homeostasis during zebrafish development, which in turn may support a role of lxr for normal development of the central nervous sytem, including the retina.

  • 31. Archer, Amena
    et al.
    Lauter, Gilbert
    Södertörns högskola, Institutionen för livsvetenskaper.
    Hauptmann, Giselbert
    Södertörns högskola, Institutionen för livsvetenskaper.
    Mode, Agneta
    Gustafsson, Jan-Ake
    Transcriptional activity and developmental expression of liver X receptor (lxr) in zebrafish2008Inngår i: Developmental Dynamics, ISSN 1058-8388, E-ISSN 1097-0177, Vol. 237, nr 4, 1090-1098 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Mammalian liver-X-receptors (LXRs) are transcription factors activated by oxysterols. They play an essential role in lipid and glucose metabolism. We have cloned the open reading frame of zebrafish lxr and describe its genomic organization. Zebrafish lxr encodes a 50-kDa protein with high sequence similarity to mammalian LXR alpha. In transfection assays, the encoded protein showed transcriptional activity in response to LXR-ligands. Treatment of adult zebrafish with the synthetic LXR ligand, GW3965, induced expression of genes involved in hepatic cholesterol and lipid pathways. Using qPCR and in situ hybridization, we found ubiquitous expression of lxr mRNA during the first 24 hr of development, followed by more restricted expression, particularly to the liver at 3dpf and the liver and intestine at 4dpf. In adult fish, all examined organs expressed lxr. In addition to a metabolic role of lxr, the temporal expression pattern suggests a developmental role in, e.g., the liver and CNS.

  • 32.
    Arcot Jayaram, Satish
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    New roles for apical secretion and extracellular matrix assembly in Drosophila epithelial morphogenesis2010Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Branched tubular organs, such as the lung and vascular system fulfill the respiratory needs of most animals. Optimal tissue function relies on the uniform sizes and shapes of the constituting branches in each organ. The Drosophila tracheal airways provide a recognized genetic model system for identification and characterization of tube size regulators. We found that the programmed secretion and assembly of the apical extracellular matrix (ECM) is required for the expansion of the trachea and salivary glands (SG) tubes. We have characterized Vermiform (Verm) and Serpentine (Serp), two chitin-binding proteins with predicted polysaccharide deacetylase domains (ChLDs). Verm and Serp mutants show overelongated tubes, suggesting that luminal ECM modification restricts tracheal tube elongation. The luminal deposition of ChLDs, but not other secreted components, depends on paracellular septate junction integrity (SJs) in the tracheal epithelium. Deletion of the deacetylase domain renders Serp-GFP intracellular, arguing that the deacetylase domain harbors uncharacterized secretion signals. To explore this possibility we transferred the deacetylase domain from Serp to Gasp, another tracheal luminal protein, which requires the Emp24 adaptor for ER exit. The Gasp-Deac-GFP chimera was normally secreted in emp24 mutants indicating that the deacetylase domain contains potential ER-exit signals. To identify such signals we characterized conserved sequence motifs in the Serp deacetylase domain. Mutations of the N-glycosylation sites gradually reduced Serp-GFP luminal deposition suggesting that increased glycosylation enhances apical Serp secretion. By contrast, substitutions in three conserved amino acid stretches completely blocked the ER-exit of Serp-GFP. The mutated proteins were N-glycosylated suggesting that the motifs may be involved in a subsequent protein-folding step or facilitate ER exit through interactions with unidentified specific adaptors.

  • 33.
    Aresh, Bejan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Genetisk utvecklingsbiologi.
    Peuckert, Christiane
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Dissection and Culture of Mouse Embryonic Kidney2017Inngår i: Journal of Visualized Experiments, ISSN 1940-087X, E-ISSN 1940-087X, nr 123, e55715Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The goal of this protocol is to describe a method for the dissection, isolation, and culture of mouse metanephric rudiments. During mammalian kidney development, the two progenitor tissues, the ureteric bud and the metanephric mesenchyme, communicate and reciprocally induce cellular mechanisms to eventually form the collecting system and the nephrons of the kidney. As mammalian embryos grow intrauterine and therefore are inaccessible to the observer, an organ culture has been developed. With this method, it is possible to study epithelial-mesenchymal interactions and cellular behavior during kidney organogenesis. Furthermore, the origin of congenital kidney and urogenital tract malformations can be investigated. After careful dissection, the metanephric rudiments are transferred onto a filter that floats on culture medium and can be kept in a cell culture incubator for several days. However, one must be aware that the conditions are artificial and could influence the metabolism in the tissue. Also, the penetration of test substances could be limited due to the extracellular matrix and basal membrane present in the explant. One main advantage of organ culture is that the experimenter can gain direct access to the organ. This technology is cheap, simple, and allows a large number of modifications, such as the addition of biologically active substances, the study of genetic variants, and the application of advanced imaging techniques.

  • 34.
    Arvola, Marie
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för evolutionsbiologi.
    Immunological aspects of maternal-foetal interactions in mice2001Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Mammalian pregnancy is an immunological paradox. The foetus, which expresses both paternal and maternal cell-surface molecules, has to be protected from rejection by the maternal immune system. At the same time, the mother has to have an efficient immune defence and must provide her offspring with antibodies.

    The first part of this thesis investigates some of the mechanisms involved in the foetal avoidance of maternal rejection reactions. Placental absence of MHC class II expression, as well as a bias for Th2-cytokines at the maternal-foetal interface are suggested to be important for foetal survival. The results showed that placental MHC class II expression cannot be induced in vivo. Transfections of trophoblast cells with MHC class II genes, however, resulted in detectable MHC class II cell-surface expression, indicating that a post-transcriptional block does not exist in these cells.

    By using IL-4- and IL-10-double deficient mice, it was shown that neither maternal nor foetal expression of these cytokines were crucial for completion of allogeneic pregnancy.

    In the second part of the thesis, the effect of transmission of immunoglobulin G (IgG) from the mother to the offspring was studied. It was observed that viable maternal Ig-secreting cells occasionally infiltrated the B cell-deficient offspring and remained functional for long periods. In this study "green fluorescent mice" were used as a tool. Furthermore, neonatal ingestion of wild type milk increased the survival of adoptively transferred B-lineage cells in B cell-deficient mice, suggesting that suckling of IgG-containing milk could be used to facilitate B cell-reconstitution in B cell-deficient mice. Finally, results from studies on normal mice showed that absence of maternal IgG-transmission during their neonatal development resulted in elevated serum-IgG production, as well as enhanced immune reactions upon immunisations in adult life. This showed that maternal IgG can have long-term immunoregulatory effects in the offspring.

  • 35.
    Bahrami, Fariba
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för evolutionsbiologi.
    Methylsulphonyl-chlorobenzenes and the olfactory system: Comparative toxicity of the 2,5- and 2,6-dichlorinated isomers in mice2000Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Methyl sulphone metabolites of chlorinated aryl hydrocarbons are persistentenvironmental pollutants that can bioaccumulate in animals and humans. Little is known about the toxicological effects of these metabolites and this thesis is an attempt to increase this limited knowledge. Tissue-binding, toxicity and neuro-behavioural effects of methylsulphonyl-2,6dichlorobenzene [2,6-(diCl-MeSO2-B)] and methylsulphonyl-2,5-dichlorobenzene [2,5-(diCl-MeSO2-B)] were examined on mice.

    Both substances resulted in a strong uptake in the olfactory mucosa (OM). Only 2,6-(diCl-MeSO2-B) induced toxicity in the OM, originating from a primary lesion in the Bowman's glands (BG). An in situ CYP-catalysed activation of 2,6-(diCl-MeSO2-B) seems to occur in the BG giving rise to reactive intermediates which either conjugate with glutathione or induce local toxicity. Subsequent secondary lesions in the OM include: severe degenerationof the neuroepithelium, fibrosis, ossification and polyposis. These effects resulted from a single ip dose and were permanent. Long lasting induction of GFAP in the olfactory bulb (OB) and behavioural deficits were also observed and considered to be caused by damaged olfactory neurons and/or metabolites translocated to the OB. Although the OM was more damaged in male mice, acquisition deficits occurred only in female mice.

    2,5-(diCl-MeSO2-B) did not induce OM toxicity, GFAP or learning deficits in either sex. However, observed motor activity responses indicate that, although 2,5-(diCl-MeSO2-B) is not olfacto-toxic, it is neuro-toxic.

    1,3-Dichloro-, 1,4-dichloro- or 1,2,3-trichloro-benzene did not induce damage in the OM indicating that an electron withdrawing substituent in the primary position and 2,6-positioned chlorine atoms is a structural requirement for OM toxicity. Persistent, dose-, time-, tissue- and sex-dependent effects on the olfactory system induced by 2,6-(diCl-MeS2-B) together with the lack of lesions in the OM or brain by 2,5-(diCl-MeSO2-B), makes this chemical pair a reliable and versatile tool for olfactory research.

  • 36.
    Bahrampour, Shahrzad
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Genetic mechanisms regulating proliferation and cell specification in the Drosophila embryonic CNS2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The central nervous system (CNS) consists of an enormous number of cells, and large cellular variance, integrated into an elaborate network. The CNS is the most complex animal organ, and therefore its establishment must be controlled by many different genetic programs. Considering the high level of complexity in the human CNS, addressing issues related to human neurodevelopment represents a major challenge. Since comparative studies have revealed that neurodevelopmental programs are well conserved through evolution, on both the genetic and functional levels, studies on invertebrate neurodevelopmental programs are often translatable to vertebrates. Indeed, the basis of our current knowledge about vertebrate CNS development has been greatly aided by studies on invertebrates, and in particular on the Drosophila melanogaster (fruit fly) model system.

    This thesis attempted to identify novel genes regulating neural cell specification and proliferation in the CNS, using the Drosophila model system. Moreover, I aimed to address how those genes govern neural progenitor cells (neuroblasts; NBs) to obtain/maintain their stemness identity and proliferation capacity, and how they drive NBs through temporal windows and series of programmed asymmetric division, which gradually reduces their stemness identity in favor of neural differentiation, resulting in appropriate lineage progression. In the first project, we conducted a forward genetic screen in Drosophila embryos, aimed at isolating genes involved in regulation of neural proliferation and specification, at the single cell resolution. By taking advantage of the restricted expression of the neuropeptide FMRFa in the last-born cell of the NB lineage 5-6T, the Ap4 neuron, we could monitor the entire lineage progression. This screen succeeded in identifying 43 novel genes controlling different aspects of CNS development. One of the genes isolated, Ctr9, displayed extra Ap4/FMRFa neurons. Ctr9 encodes a component of the RNA polymerase II complex Paf1, which is involved in a number of transcriptional processes. The Paf1C, including Ctr9, is highly conserved from yeast to human, and in the past couple of years, its importance for transcription has become increasingly appreciated. However, studies in the Drosophila system have been limited. In the screen, we isolated the first mutant of Drosophila Ctr9 and conducted the first detailed phenotypic study on its function in the Drosophila embryonic CNS. Loss of function of Ctr9 leads to extra NB numbers, higher proliferation ratio and lower expression of neuropeptides. Gene expression analysis identified several other genes regulated by Ctr9, which may explain the Ctr9 mutant phenotypes. In summary, we identified Ctr9 as an essential gene for proper CNS development in Drosophila, and this provides a platform for future study on the Drosophila Paf1C. Another interesting gene isolated in the screen was worniou (wor), a member of the Snail family of transcription factors. In contrast to Ctr9, whichdisplayed additional Ap4/FMRFa neurons, wor mutants displayed a loss of these neurons. Previous studies in our group have identified many genes acting to stop NB lineage progression, but how NBs are pushed to proliferate and generate their lineages was not well known. Since wor may constitute a “driver” of proliferation, we decided to study it further. Also, we identified five other transcription factors acting together with Wor as pro-proliferative in both NBs and their daughter cells. These “drivers” are gradually replaced by the previously identified late-acting “stoppers.” Early and late factors regulate each other and the cell cycle, and thereby orchestrate proper neural lineage progression.

  • 37.
    Bahrampour, Shahrzad
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Gunnar, Erika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Jönsson, Carolin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Ekman, Helen
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Thor, Stefan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Neural Lineage Progression Controlled by a Temporal Proliferation Program.2017Inngår i: Developmental Cell, ISSN 1534-5807, E-ISSN 1878-1551, Vol. 43, nr 3, 332-348 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Great progress has been made in identifying transcriptional programs that establish stem cell identity. In contrast, we have limited insight into how these programs are down-graded in a timely manner to halt proliferation and allow for cellular differentiation. Drosophila embryonic neuroblasts undergo such a temporal progression, initially dividing to bud off daughters that divide once (type I), then switching to generating non-dividing daughters (type 0), and finally exiting the cell cycle. We identify six early transcription factors that drive neuroblast and type I daughter proliferation. Early factors are gradually replaced by three late factors, acting to trigger the type I→0 daughter proliferation switch and eventually to stop neuroblasts. Early and late factors regulate each other and four key cell-cycle genes, providing a logical genetic pathway for these transitions. The identification of this extensive driver-stopper temporal program controlling neuroblast lineage progression may have implications for studies in many other systems.less thanbr /greater than (Copyright © 2017 Elsevier Inc. All rights reserved.)

  • 38.
    Barsoum, Emad
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Mating type switching and transcriptional silencing in Kluyveromyces lactis2010Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    To explore the similarities and differences of regulatory circuits among budding yeasts, we characterized the role of unscheduled meiotic gene expression 6 (UME6) and a novel mating type switching pathway in Kluyveromyces lactis. We found that Ume6 was required for transcriptional silencing of the cryptic mating-type loci HMLα and HMRa. Ume6 acted directly at these loci by binding to the cis-regulatory silencers. Ume6 also served as a block to polyploidy and was required for repression of three meiotic genes, independently of the Rpd3 and Sin3 corepressors.

    Mating type switching from MATα to MATa required the α3 protein. The α3 protein was similar to transposases of the mutator like elements (MULEs). Mutational analysis showed that the DDE-motif in α3, which is conserved in MULEs was necessary for switching. During switching α3 mobilizes from the genome in the form of a DNA circle. The sequences encompassing the α3 gene circle junctions in the MATα locus were essential for switching from MATα to MATa. Switching also required a DNA binding protein, Mating type switch 1 (Mts1), whose binding sites in MATα were important. Expression of Mts1 was repressed in MATa/MATα diploids and by nutrients, limiting switching to haploids in low nutrient conditions.

    In a genetic selection for strains with increased switching rates we found a mutation in the RAS1 gene. By measuring the levels of the MTS1 mRNA and switching rates in ras1, pde2 and msn2 mutant strains we show that mating type switching in K. lactis was regulated by the RAS/cAMP pathway and the transcription factor Msn2. ras1 mutants contained 20-fold higher levels of MTS1 mRNA compared to wild type whereas pde2 and msn2 expressed less MTS1 mRNA and had decreased switching rates. Furthermore we found that MTS1 contained several potential Msn2 binding sites upstream of its ORF. We suggest that these observations explain the nutrient regulation of switching.

  • 39.
    Barsoum, Emad
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för utvecklingsbiologi.
    Martinez, Paula
    Åström, Stefan U.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för utvecklingsbiologi.
    {alpha}3, a transposable element that promotes host sexual reproduction2010Inngår i: Genes & Development, ISSN 0890-9369, E-ISSN 1549-5477, Vol. 24, nr 15, 33-44 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Theoretical models predict that selfish DNA elements require host sex to persist in a population. Therefore, a transposon that induces sex would strongly favor its own spread. We demonstrate that a protein homologous to transposases, called alpha3, was essential for mating type switch in Kluyveromyces lactis. Mutational analysis showed that amino acids conserved among transposases were essential for its function. During switching, sequences in the 5' and 3' flanking regions of the alpha3 gene were joined, forming a DNA circle, showing that alpha3 mobilized from the genome. The sequences encompassing the alpha3 gene circle junctions in the mating type alpha (MATalpha) locus were essential for switching from MATalpha to MATa, suggesting that alpha3 mobilization was a coupled event. Switching also required a DNA-binding protein, Mating type switch 1 (Mts1), whose binding sites in MATalpha were important. Expression of Mts1 was repressed in MATa/MATalpha diploids and by nutrients, limiting switching to haploids in low-nutrient conditions. A hairpin-capped DNA double-strand break (DSB) was observed in the MATa locus in mre11 mutant strains, indicating that mating type switch was induced by MAT-specific DSBs. This study provides empirical evidence for selfish DNA promoting host sexual reproduction by mediating mating type switch.

  • 40.
    Barsoum, Emad
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för utvecklingsbiologi.
    Sjöstrand, Jimmy O. O.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för utvecklingsbiologi.
    Åström, Stefan U.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för utvecklingsbiologi.
    Ume6 is required for the MATa/MATα cellular identity and transcriptional silencing in Kluyveromyces lactis2010Inngår i: Genetics, ISSN 0016-6731, E-ISSN 1943-2631, Vol. 184, nr 4, 999-1011 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To explore the similarities and differences of regulatory circuits among budding yeasts, we characterized the role of the unscheduled meiotic gene expression 6 (UME6) gene in Kluyveromyces lactis. We found that Ume6 was required for transcriptional silencing of the cryptic mating-type loci HMLα and HMRa. Chromatin immunoprecipitation (ChIP) suggested that Ume6 acted directly by binding the cis-regulatory silencers of these loci. Unexpectedly, a MATa ume6 strain was mating proficient, whereas a MATα ume6 strain was sterile. This observation was explained by the fact that ume6 derepressed HMLα2 only weakly, but derepressed HMRa1 strongly. Consistently, two a/α-repressed genes (MTS1 and STE4) were repressed in the MATα ume6 strain, but were expressed in the MATa ume6 strain. Surprisingly, ume6 partially suppressed the mating defect of a MATa sir2 strain. MTS1 and STE4 were repressed in the MATa sir2 ume6 double-mutant strain, indicating that the suppression acted downstream of the a1/α2-repressor. We show that both STE12 and the MATa2/HMRa2 genes were overexpressed in the MATa sir2 ume6 strain. Consistent with the idea that this deregulation suppressed the mating defect, ectopic overexpression of Ste12 and a2 in a MATa sir2 strain resulted in efficient mating. In addition, Ume6 served as a block to polyploidy, since ume6/ume6 diploids mated as pseudo a-strains. Finally, Ume6 was required for repression of three meiotic genes, independently of the Rpd3 and Sin3 corepressors.

  • 41.
    Barsoum, Emad
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för utvecklingsbiologi.
    Åström, Stefan
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för utvecklingsbiologi.
    Regulation of mating type switching in Kluyveromyces lactis by the RAS/cAMP pathway and the transcription factor Msn2Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    We explored the regulation of mating type switching in Kluyveromyces lactis. Using an assay dependent on loss of a URA3 gene inserted into the MATa locus, we determined that the switching rate of a wild type strain grown in rich media was ~6X10-4 events/generation. In a genetic selection for identifying strains with increased switching rates, we found a strain with an insertion in the K. lactis RAS1 gene, encoding a small GTPase with a central role in growth regulation. Compromised Ras1 function leads to a lower cAMP level suggesting a role for cAMP in promoting switching. Consistent with this idea, a strain lacking the PDE2 gene, which encodes an enzyme that degrades cAMP, resulted in decreased switching rates. To explore how cAMP regulated switching, we investigated the transcription of the MTS1 gene, encoding an inducer of switching. The ras1 mutant strain contained 20-fold higher levels of the MTS1 mRNA compared to wild type, but in the pde2 mutant strain MTS1 transcription was repressed 5-fold. In addition, strains lacking the MSN2 gene, which encodes a transcription factor that binds the stress response element (STRE), expressed less MTS1 mRNA and had decreased switching rates. We suggest a model in which nutrient limitation induces switching through cAMP and Msn2-dependent transcriptional induction of the MTS1 gene.

  • 42. Barton, S C
    et al.
    Arney, K L
    Shi, Wei
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Zoologisk utvecklingsbiologi.
    Niveleau, A
    Fundele, Reinald
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Zoologisk utvecklingsbiologi.
    Surani, M A
    Haaf, T
    Genome-wide methylation patterns in normal and uniparental early mouse embryos2001Inngår i: Human Molecular Genetics, ISSN 0964-6906, Vol. 10, nr 26, 2983-7 s.Artikkel i tidsskrift (Fagfellevurdert)
  • 43.
    Baumgardt, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Utvecklingsbiologi, IKE. Linköpings universitet, Hälsouniversitetet.
    Genetic mechanisms behind cell specification in the Drosophila CNS2009Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The human central nervous system (CNS) contains a daunting number of cells and tremendous cellular diversity. A fundamental challenge of developmental neurobiology is to address the questions of how so many different types of neurons and glia can be generated at the precise time and place, making precisely the right connections. Resolving this issue involves dissecting the elaborate genetic networks that act within neurons and glia, as well as in the neural progenitor cells that generates them, to specify their identities.

    My PhD project has involved addressing a number of unresolved issues pertaining to how neural progenitor cells are specified to generate different types of neurons and glial cells in different temporal and spatial domains, and also how these early temporal and spatial cues are integrated to activate late cell fate determinants, which act in post-mitotic neural cells to activate distinct batteries of terminal differentiation genes.

    Analyzing the development of a specific Drosophila melanogaster (Drosophila) CNS stem cell – the neuroblast 5-6 (NB5-6) – we have identified several novel mechanisms of cell fate specification in the Drosophila CNS. We find that, within this lineage, the differential specification of a group of sequentially generated neurons – the Ap cluster neurons – is critically dependent upon the simultaneous triggering of two opposing feed-forward loops (FFLs) within the neuroblast. The first FFL involves cell fate determinants and progresses within the post-mitotic neurons to establish a highly specific combinatorial code of regulators, which activates a distinct battery of terminal differentiation genes. The second loop, which progresses in the neuroblast, involves temporal and sub-temporal genes that together oppose the progression of the first FFL. This leads to the establishment of an alternative code of regulators in late-born Ap cluster neurons, whereby alternative cell fates are specified. Furthermore, we find that the generation and specification of the Ap cluster neurons is modulated along the neuraxis by two different mechanisms. In abdominal segments, Hox genes of the Bithorax cluster integrates with Pbx/Meis factors to instruct NB5-6 to leave the cell cycle before the Ap cluster neurons are generated. In brain segments, Ap cluster neuron equivalents are generated, but improperly specified due to the absence of the proper Hox and temporal code. Additionally, in thoracic segments we find that the specification of the Ap cluster neurons is critically dependent upon the integration of the Hox, Pbx/Meis, and the temporal genes, in the activation of the critical cell fate determinant FFL.

    We speculate that the developmental principles of (i) feed-forward combinatorial coding; (ii) simultaneously triggered yet opposing feed-forward loops; and (iii) integration of different Hox, Pbx/Meis, and temporal factors, at different axial levels to control inter-segmental differences in lineage progression and specification; might be used widely throughout the animal kingdom to generate cell type diversity in the CNS.

  • 44.
    Baumgardt, Magnus
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Utvecklingsbiologi. Linköpings universitet, Hälsouniversitetet.
    Karlsson, Daniel
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Utvecklingsbiologi. Linköpings universitet, Hälsouniversitetet.
    Terriente, Javier
    Division of Developmental Neuroscience, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom.
    Díaz-Benjumea, Fernando J.
    Centro de Biología Molecular-Severo Ochoa/C.S.I.C., Universidad Autónoma-Cantoblanco, Madrid 28049, Spain.
    Thor, Stefan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Utvecklingsbiologi. Linköpings universitet, Hälsouniversitetet.
    Neuronal Subtype Specification within a Lineage by Opposing Temporal Feed-Forward Loops2009Inngår i: Cell, ISSN 0092-8674, E-ISSN 1097-4172, Vol. 139, nr 5, 969-982 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Neural progenitors generate distinct cell types at different stages, but the mechanisms controlling these temporal transitions are poorly understood. In the Drosophila CNS, a cascade of transcription factors, the ‘temporal gene cascade’, has been identified, that acts to alter progenitor competence over time. However, many CNS lineages display broad temporal windows, and it is unclear how broad windows progress into sub-windows that generate unique cell types. We have addressed this issue in an identifiable Drosophila CNS lineage, and find that a broad castor temporal window is sub-divided by two different feed-forward loops, both of which are triggered by castor itself. The first loop acts to specify a unique cell fate, while the second loop suppresses the first loop, thereby allowing for the generation of alternate cell fates. This mechanism of temporal and ‘sub-temporal’ genes acting in opposing feed-forward loops may be used by many stem cell lineages to generate diversity.

  • 45.
    Bekele, Tesfaye
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolutionsbiologi.
    Plant Population Dynamics of Dodonaea angustifolia and Olea europaea ssp. cuspidata in Dry Afromontane Forests of Ethiopia2000Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Human disturbance has led to excessive deforestation and to a very limited forest cover in the Afromontane zone of Ethiopia, which forms a large part of the country. Thus urgent conservation measures are required to ameliorate the situation. Understanding the natural regeneration processes and the dynamics of plant populations of tree and shrub species has a practical application in the restoration of these habitats.

    The present study focuses on the population dynamics and regeneration of an early successional shrub Dodonaea angustifolia and a late successional tree Olea europaea ssp. cuspidata in southern Wello, Ethiopia. Population structure and dynamics, regeneration and seed banks in dry Afromontane habitats were considered.

    For both species, three population structure patterns were identified: 1) high density, reversed J-shape structure with many seedlings and few large individuals, 2) lower density, unimodal structure with higher proportions of plants of intermidiate size, 3) high density with higher proportions of large plants , in some cases bimodal with small and large individuals. Vegetation type and protection time were found to have a significant effect on the population structure of both species. Dodonaea can establish itself on degraded land, once the disturbance has ceased

    Projection matrix analysis on observations from permanent plots in Dodonaea populations in protected and unprotected sites resulted in one declining population, and one increasing in the protected site and declining populations at the unprotected site. The overall projected growth rate in Dodonaea calculated from a pooled matrix indicated positive population growth. The factors influencing the population growth, recruitment and survival are discussed.

    The persistence of Olea populations seems to depend on the more stable environmental conditions in later successional stages of forest vegetation. There are possibilities of natural regeneration of Olea if regenerating individuals still occur in the area. Rainfall seasonality is a dominant factor in regulating establishment, recruitment, survival and growth, particularly during the seedling stage. Moreover, shade and herbivory are factors that need consideration. Since Olea grows better under shade than in the open sun, successful regeneration for this species relies on shade from other plants and on protection from grazing, at least during the seedling stage.

    Most of the species that germinated from the seed banks were herbs and grasses with very few shrub and tree species. There was low correspondence between species composition of the seed banks and that of the standing vegetation.

    Spatial and temporal variation in demographic parameters among populations of Dodonaea and Olea can be attributed to human and environmental influence. Under protection, both Dodonaea and Olea seem to have a possibility to regenerate naturally. Further research should consider factors mentioned in detailed investigations of other dominant Afromontane forest species.

  • 46.
    Beltran-Pardo, Eliana
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Jonsson, K. Ingemar
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. Kristianstad University, Sweden.
    Harms-Ringdahl, Mats
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Haghdoost, Siamak
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Tolerance to Gamma Radiation in the Tardigrade Hypsibius dujardini from Embryo to Adult Correlate Inversely with Cellular Proliferation2015Inngår i: PLoS ONE, ISSN 1932-6203, Vol. 10, nr 7, e0133658Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Tardigrades are highly tolerant to desiccation and ionizing radiation but the mechanisms of this tolerance are not well understood. In this paper, we report studies on dose responses of adults and eggs of the tardigrade Hypsibius dujardini exposed to gamma radiation. In adults the LD50/48h for survival was estimated at similar to 4200 Gy, and doses higher than 100 Gy reduced both fertility and hatchability of laid eggs drastically. We also evaluated the effect of radiation (doses 50 Gy, 200 Gy, 500 Gy) on eggs in the early and late embryonic stage of development, and observed a reduced hatchability in the early stage, while no effect was found in the late stage of development. Survival of juveniles from irradiated eggs was highly affected by a 500 Gy dose, both in the early and the late stage. Juveniles hatched from eggs irradiated at 50 Gy and 200 Gy developed into adults and produced offspring, but their fertility was reduced compared to the controls. Finally we measured the effect of low temperature during irradiation at 4000 Gy and 4500 Gy on survival in adult tardigrades, and observed a slight delay in the expressed mortality when tardigrades were irradiated on ice. Since H. dujardini is a freshwater tardigrade with lower tolerance to desiccation compared to limno-terrestrial tardigrades, the high radiation tolerance in adults, similar to limno-terrestrial tardigrades, is unexpected and seems to challenge the idea that desiccation and radiation tolerance rely on the same molecular mechanisms. We suggest that the higher radiation tolerance in adults and late stage embryos of H. dujardini (and in other studied tardigrades) compared to early stage embryos may partly be due to limited mitotic activity, since tardigrades have a low degree of somatic cell division (eutely), and dividing cells are known to be more sensitive to radiation.

  • 47.
    Benito-Sipos, Jonathan
    et al.
    Centro de Biología Molecular-Severo Ochoa, Universidad Autónoma de Madrid-C.S.I.C., Madrid, Spain.
    Estacio-Gómez, Alicia
    Centro de Biología Molecular-Severo Ochoa, Universidad Autónoma de Madrid-C.S.I.C., Madrid, Spain.
    Moris-Sanz, Marta
    Centro de Biología Molecular-Severo Ochoa, Universidad Autónoma de Madrid-C.S.I.C., Madrid, Spain.
    Baumgardt, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Utvecklingsbiologi, IKE. Linköpings universitet, Hälsouniversitetet.
    Thor, Stefan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Utvecklingsbiologi, IKE. Linköpings universitet, Hälsouniversitetet.
    Díaz-Benjumea, Fernando J.
    Centro de Biología Molecular-Severo Ochoa, Universidad Autónoma de Madrid-C.S.I.C., Madrid, Spain.
    A genetic cascade involving the genes klumfuss, nab and castor specifies the abdominal leucokinergic neurons in the Drosophila CNSManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    The genetic mechanisms underlying the specification of a large number of different cell fates starting from a limited group of progenitor cells are a major focus of investigations of central nervous system development. In Drosophila the identities of the different neuronal progenitor cells, the neuroblasts, are specified by a combination of spatial and temporal factors. But how each neuroblast gives rise to a specific repertoire of cell types via a precise programme is poorly understood. In this report we analyse the specification of a small set of peptidergic cells, the abdominal leucokinergic neurons. We identify the progenitors of these neurons, the temporal window in which they are specified, and the influence of the Notch signalling pathway on their specification. We also show that the products of the genes klumfuss, nab and castor play important roles in their specification via a genetic cascade.

  • 48.
    Bentley, Katie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Vaskulärbiologi. Harvard Med Sch, Beth Israel Deaconess Med Ctr, Computat Biol Lab, Boston, MA USA..
    Chakravartula, Shilpa
    Harvard Med Sch, Beth Israel Deaconess Med Ctr, Computat Biol Lab, Boston, MA USA..
    The temporal basis of angiogenesis2017Inngår i: Philosophical Transactions of the Royal Society of London. Biological Sciences, ISSN 0962-8436, E-ISSN 1471-2970, Vol. 372, nr 1720, 1-11 s., 20150522Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The process of new blood vessel growth (angiogenesis) is highly dynamic, involving complex coordination of multiple cell types. Though the process must carefully unfold over time to generate functional, well-adapted branching networks, we seldom hear about the time-based properties of angiogenesis, despite timing being central to other areas of biology. Here, we present a novel, time-based formulation of endothelial cell behaviour during angiogenesis and discuss a flurry of our recent, integrated in silico/in vivo studies, put in context to the wider literature, which demonstrate that tissue conditions can locally adapt the timing of collective cell behaviours/decisions to grow different vascular network architectures. A growing array of seemingly unrelated 'temporal regulators' have recently been uncovered, including tissue derived factors (e.g. semaphorins or the high levels of VEGF found in cancer) and cellular processes (e.g. asymmetric cell division or filopodia extension) that act to alter the speed of cellular decisions to migrate. We will argue that 'temporal adaptation' provides a novel account of organ/disease-specific vascular morphology and reveals 'timing' as a new target for therapeutics. We therefore propose and explain a conceptual shift towards a 'temporal adaptation' perspective in vascular biology, and indeed other areas of biology where timing remains elusive. This article is part of the themed issue 'Systems morphodynamics: understanding the development of tissue hardware'.

  • 49. Benton, Jeanne
    et al.
    Kery, Rachel
    Li, Jingjing
    Noonin, Chadanat
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Jämförande fysiologi.
    Söderhäll, Irene
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Jämförande fysiologi.
    Beltz, Barbara
    Cells from the Immune System Generate Adult-Born Neurons in Crayfish2014Inngår i: Developmental Cell, ISSN 1534-5807, E-ISSN 1878-1551, Vol. 30, nr 3, 322-333 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Neurogenesis is an ongoing process in the brains of adult decapod crustaceans. However, the first-generation precursors that produce adult-born neurons, which reside in a neurogenic niche, are not self-renewing in crayfish and must be replenished. The source of these neuronal precursors is unknown. Here, we report that adult-born neurons in crayfish can be derived from hemocytes. Following adoptive transfer of 5-ethynyl-2′-deoxyuridine (EdU)-labeled hemocytes, labeled cells populate the neurogenic niche containing the first-generation neuronal precursors. Seven weeks after adoptive transfer, EdU-labeled cells are located in brain clusters 9 and 10 (where adult-born neurons differentiate) and express appropriate neurotransmitters. Moreover, the number of cells composing the neurogenic niche in crayfish is tightly correlated with total hemocyte counts (THCs) and can be manipulated by raising or lowering THC. These studies identify hemocytes as a source of adult-born neurons in crayfish and demonstrate that the immune system is a key contributor to adult neurogenesis.

  • 50.
    Benton, JL
    et al.
    Wellesley Coll, Neurosci. Program, Wellesley.
    Zhang, Y
    Wellesley Coll, Neurosci. Program, Wellesley.
    Söderhäll, Irene
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Jämförande fysiologi.
    Beltz, BS
    Wellesley Coll, Neurosci. Program, Wellesley, MA 02181 USA .
    The crustacean cytokine astakine-1: a link between adult neurogenesis and hematopoiesis?2012Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Adult neurogenesis occurs in the brains of vertebrate and invertebrate species. In the crayfish Procambarus clarkii, neurogenic niches located on the ventral surface of the brain contain the 1st-generation precursors that produce adult-born neurons. These cells divide symmetrically and both daughter cells migrate in streams to proliferation zones in interneuronal cell clusters, where they divide at least one more time. Double-nucleoside labeling has confirmed that the 1st-generation neuronal precursors are not self-renewing. However, previous studies have shown that the niche is not depleted and, further, that niche cell numbers increase throughout the animal’s lifetime (Zhang et al., 2009). Our goal, therefore, is to identify the source of niche cells and in particular the 1st-generation neuronal precursors. Experiments have revealed that hemocytes, and in particular semi-granular cells, are attracted to and incorporated into the niches of dissected intact brains in culture; cell types from other tissues show no affinity for the niche (Benton et al., 2011). Lin et al. (2010) demonstrated that a prokineticin family cytokine, astakine-1, promotes the differentiation and release of semi-granular cells from hematopoietic tissue. In the present studies, we have injected astakine-1 into crayfish and examined subsequent changes in niche cell numbers, as well as BrdU incorporation into cells in the niche, streams and proliferation zones. By 48 hrs following astakine-1 injection, three alterations in the neurogenic system have been demonstrated: (1) increased total numbers of cells in the neurogenic niche compared to saline-injected shams; (2) increased BrdU-incorporation into cells in the niche, streams and proliferation zone in cell cluster 10; (3) increased probability of observing cells within the vascular cavity in the niche, implying that the numbers of cells interacting with the niche is upregulated. These experiments exploring the relationship between the hematopoietic system and adult neurogenesis suggest that cells released from hematopoietic tissues following astakine-1 injection influence the cellular composition of the niche and the rate of BrdU-incorporation into niche cells.

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