Logotyp: till Uppsala universitets webbplats

uu.sePublikationer från Uppsala universitet
Ändra sökning
Avgränsa sökresultatet
1234567 1 - 50 av 1054
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Träffar per sida
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
Markera
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 1.
    Abbott, Jessica K.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Zooekologi.
    Bedhomme, Stéphanie
    Evolutionary Systems Virology Group, University of Valencia.
    Chippindale, Adam K.
    Biology Department, Queen's University.
    Sexual conflict in wing size and shape in Drosophila melanogaster2010Ingår i: Journal of Evolutionary Biology, ISSN 1010-061X, E-ISSN 1420-9101, Vol. 23, nr 9, s. 1989-1997Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Intralocus sexual conflict occurs when opposing selection pressures operate on loci expressed in both sexes, constraining the evolution of sexual dimorphism and displacing one or both sexes from their optimum. We eliminated intralocus conflict in Drosophila melanogaster by limiting transmission of all major chromosomes to males, thereby allowing them to win the intersexual tug-of-war. Here, we show that this male-limited (ML) evolution treatment led to the evolution (in both sexes) of masculinized wing morphology, body size, growth rate, wing loading, and allometry. In addition to more male-like size and shape, ML evolution resulted in an increase in developmental stability for males. However, females expressing ML chromosomes were less developmentally stable, suggesting that being ontogenetically more male-like was disruptive to development. We suggest that sexual selection over size and shape of the imago may therefore explain the persistence of substantial genetic variation in these characters and the ontogenetic processes underlying them.

    Ladda ner fulltext (pdf)
    FULLTEXT03
  • 2.
    Abbott, Jessica K.
    et al.
    Queen's University.
    Gosden, Thomas P.
    Lund University.
    Correlated morphological and colour differences among females of the damselfly Ischnura elegans2009Ingår i: Ecological Entomology, ISSN 0307-6946, E-ISSN 1365-2311, Vol. 34, nr 3, s. 378-386Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    1. The female-limited colour polymorphic damselfly Ischnura elegans has proven to be an interesting study organism both as an example of female sexual polymorphism, and in the context of the evolution of colour polymorphism. The study of colour polymorphism can also have broader applications as a model of speciation processes.

    2. Previous research suggests that there exist correlations between colour morph and other phenotypic traits, and that the different female morphs in I. elegans may be pursuing alternative phenotypically integrated strategies. However, previous research on morphological differences in southern Swedish individuals of this species was only carried out on laboratory-raised offspring from a single population, leaving open the question of how widespread such differences are.

    3. We therefore analysed multi-generational data from 12 populations, investigating morphological differences between the female morphs in the field, differences in the pattern of phenotypic integration between morphs, and quantified selection on morphological traits.

    4. We found that consistent morphological differences did indeed exist between the morphs across all study populations, confirming that the previously observed differences were not simply a laboratory artefact.  We also found, somewhat surprisingly, that despite the existence of sexual dimorphism in body size and shape, patterns of phenotypic integration differed most between the morphs and not between the sexes. Finally, linear selection gradients showed that female morphology affected fecundity differently between the morphs.

    5. We discuss the relevance of these results to the male mimicry hypothesis and to the existence of potential ecological differences between the morphs.

    Ladda ner fulltext (pdf)
    FULLTEXT02
  • 3.
    Abbott, Jessica K.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och evolution, Zooekologi.
    Svensson, Erik I.
    Lund University.
    Morph-specific variation in intersexual genetic correlations in an intra-specific mimicry system2010Ingår i: Evolutionary Ecology Research, ISSN 1522-0613, E-ISSN 1937-3791, Vol. 12, nr 1, s. 105-118Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Positive intersexual genetic correlations are typically viewed as constraining the evolution of sexual dimorphism, when traits are subject to sexually antagonistic selection. Our study species, the damselfly Ischnura elegans, has a female-limited colour polymorphism with three female colour morphs (males are monomorphic), one of which is considered a male mimic.

    Question: Are there morph-specific differences in the magnitude of intersexual genetic correlations in I. elegans? Specifically, do male-mimic (Androchrome) females have higher intersexual genetic correlations for morphological traits than non-mimic (Infuscans) females?

    Methods: We collected copulating pairs in the field and raised offspring from these pairs in the laboratory. We measured five morphological traits in both parent and offspring generations and investigated their heritabilities and genetic correlations.

    Results: We found a negative overall relationship between the degree of sexual dimorphism for a trait and its intersexual genetic correlation. But the magnitude and direction of intersexual genetic correlations depended on the female morph. As expected, male mimic (Androchrome) females had higher intersexual genetic correlations. In addition, the genetic correlations between the morphs were in all cases significantly lower than unity. Male mimic (Androchrome) females had higher mother-son covariances than the non-mimic (Infuscans) morph, and this difference is the proximate explanation for the difference in intersexual genetic correlations between the morphs.

    Ladda ner fulltext (pdf)
    FULLTEXT02
  • 4.
    Abbott, Jessica K.
    et al.
    Lund University.
    Svensson, Erik I.
    Lund University.
    Ontogeny of sexual dimorphism and phenotypic integration in heritable morphs2008Ingår i: Evolutionary Ecology, ISSN 0269-7653, E-ISSN 1573-8477, Vol. 22, nr 1, s. 103-121Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In this study we investigated the developmental basis of adult phenotypes in a non-model organism, a polymorphic damselfly (Ischnura elegans) with three female colour morphs. This polymorphic species presents an ideal opportunity to study intraspecific variation in growth trajectories, morphological variation in size and shape during the course of ontogeny, and to relate these juvenile differences to the phenotypic differences of the discrete adult phenotypes; the two sexes and the three female morphs. We raised larvae of different families in individual enclosures in the laboratory, and traced morphological changes during the course of ontogeny. We used principal components analysis to examine the effects of Sex, Maternal morph, and Own morph on body size and body shape. We also investigated the larval fitness consequences of variation in size and shape by relating these factors to emergence success. Females grew faster than males and were larger as adults, and there was sexual dimorphism in body shape in both larval and adult stages. There were also significant effects of both maternal morph and own morph on growth rate and body shape in the larval stage. There were significant differences in body shape, but not body size, between the adult female morphs, indicating phenotypic integration between colour, melanin patterning, and body shape. Individuals that emerged successfully grew faster and had different body shape in the larval stage, indicating internal (non-ecological) selection on larval morphology. Overall, morphological differences between individuals at the larval stage carried over to the adult stage. Thus, selection in the larval stage can potentially result in correlated responses in adult phenotypes and vice versa.

    Ladda ner fulltext (pdf)
    FULLTEXT03
  • 5.
    Abbott, Jessica K.
    et al.
    Lund University.
    Svensson, Erik I.
    Lund University.
    Phenotypic and genetic variation in emergence and development time of a trimorphic damselfly2005Ingår i: Journal of Evolutionary Biology, ISSN 1010-061X, E-ISSN 1420-9101, Vol. 18, nr 6, s. 1464-1470Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Although colour polymorphisms in adult organisms of many taxa are often adaptive in the context of sexual selection or predation, genetic correlations between colour and other phenotypic traits expressed early in ontogeny could also play an important role in polymorphic systems. We studied phenotypic and genetic variation in development time among female colour morphs in the polymorphic damselfly Ischnura elegans in the field and by raising larvae in a common laboratory environment. In the field, the three different female morphs emerged at different times. Among laboratory-raised families, we found evidence of a significant correlation between maternal morph and larval development time in both sexes. This suggests that the phenotypic correlation between morph and emergence time in the field has a parallel in a genetic correlation between maternal colour and offspring development time. Maternal colour morph frequencies could thus potentially change as correlated responses to selection on larval emergence dates. The similar genetic correlation in male offspring suggests that sex-limitation in this system is incomplete, which may lead to an ontogenetic sexual conflict between selection for early male emergence (protandry) and emergence times associated with maternal morph.

    Ladda ner fulltext (pdf)
    FULLTEXT02
  • 6.
    Abdalaal, Hind
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Pundir, Shreya
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Ge, Xueliang
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylärbiologi.
    Sanyal, Suparna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylärbiologi.
    Näsvall, Joakim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Collateral toxicity limits the evolution of bacterial Release Factor 2 towards total omnipotence2020Ingår i: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 37, nr 10, s. 2918-2930Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    When new genes evolve through modification of existing genes, there are often trade-offs between the new and original functions, making gene duplication and amplification necessary to buffer deleterious effects on the original function. We have used experimental evolution of a bacterial strain lacking peptide release factor 1 (RF1) in order to study how peptide release factor 2 (RF2) evolves to compensate the loss of RF1. As expected, amplification of the RF2-encoding gene prfB to high copy number was a rapid initial response, followed by the appearance of mutations in RF2 and other components of the translation machinery. Characterization of the evolved RF2 variants by their effects on bacterial growth rate, reporter gene expression, and in vitro translation termination reveals a complex picture of reduced discrimination between the cognate and near cognate stop codons and highlight a functional trade-off that we term “collateral toxicity”. We suggest that this type of trade-off may be a more serious obstacle in new gene evolution than the more commonly discussed evolutionary trade-offs between “old” and “new” functions of a gene, as it cannot be overcome by gene copy number changes. Further, we suggest a model for how RF2 autoregulation responds not only to alterations in the demand for RF2 activity, but also for RF1 activity.

    Ladda ner fulltext (pdf)
    fulltext
  • 7.
    Abozeid, Hassanein H.
    et al.
    Cairo Univ, Fac Vet Med, Dept Poultry Dis, Giza 12211, Egypt..
    Naguib, Mahmoud
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Agr Res Ctr, Anim Hlth Res Inst, Reference Lab Vet Qual Control Poultry Prod, Giza 12618, Egypt..
    Infectious Bronchitis Virus in Egypt: Genetic Diversity and Vaccination Strategies2020Ingår i: Veterinary Sciences, E-ISSN 2306-7381, Vol. 7, nr 4, artikel-id 204Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Infectious bronchitis virus (IBV) is a highly evolving avian pathogen that has increasingly imposed a negative impact on poultry industry worldwide. In the last 20 years, IBV has been continuously circulating among chicken flocks in Egypt causing huge economic losses to poultry production. Multiple IBV genotypes, namely, GI-1, GI-13, GI-16, and GI-23 have been reported in Egypt possessing different genetic and pathogenic features. Different vaccine programs are being used to control the spread of the disease in Egypt. However, the virus continues to spread and evolve where multiple IBV variants and several recombination evidence have been described. In this review, we highlight the current knowledge concerning IBV circulation, genesis, and vaccination strategies in Egypt. In addition, we analyze representative Egyptian IBV strains from an evolutionary perspective based on available data of their S1 gene. We also provide insight into the importance of surveillance programs and share our perspectives for better control of IBV circulating in Egypt.

    Ladda ner fulltext (pdf)
    FULLTEXT01
  • 8.
    Adel, Amany
    et al.
    Anim Hlth Res Inst, Agr Res Ctr, Reference Lab Vet Qual Control Poultry Prod, Giza 12618, Egypt..
    Abdelmagid, Marwa A.
    Anim Hlth Res Inst, Agr Res Ctr, Reference Lab Vet Qual Control Poultry Prod, Giza 12618, Egypt..
    Mohamed, Ahmed Abd-Elhalem
    Anim Hlth Res Inst, Agr Res Ctr, Reference Lab Vet Qual Control Poultry Prod, Giza 12618, Egypt..
    Wasberg, Anishia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Mosaad, Zienab
    Anim Hlth Res Inst, Agr Res Ctr, Reference Lab Vet Qual Control Poultry Prod, Giza 12618, Egypt..
    Selim, Karim
    Anim Hlth Res Inst, Agr Res Ctr, Reference Lab Vet Qual Control Poultry Prod, Giza 12618, Egypt..
    Shaaban, Asmaa
    Anim Hlth Res Inst, Agr Res Ctr, Reference Lab Vet Qual Control Poultry Prod, Giza 12618, Egypt..
    Tarek, Mohamed
    Anim Hlth Res Inst, Agr Res Ctr, Reference Lab Vet Qual Control Poultry Prod, Giza 12618, Egypt..
    Hagag, Naglaa M.
    Anim Hlth Res Inst, Agr Res Ctr, Reference Lab Vet Qual Control Poultry Prod, Giza 12618, Egypt..
    Lundkvist, Åke
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Ellström, Patrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Naguib, Mahmoud
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Anim Hlth Res Inst, Agr Res Ctr, Reference Lab Vet Qual Control Poultry Prod, Giza 12618, Egypt..
    Genetic Variations among Different Variants of G1-like Avian Influenza H9N2 Viruses and Their Pathogenicity in Chickens2022Ingår i: Viruses, E-ISSN 1999-4915, Vol. 14, nr 5, artikel-id 1030Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Since it was first discovered, the low pathogenic avian influenza (LPAI) H9N2 subtype has established linages infecting the poultry population globally and has become one of the most prevalent influenza subtypes in domestic poultry. Several different variants and genotypes of LPAI H9N2 viruses have been reported in Egypt, but little is known about their pathogenicity and how they have evolved. In this study, four different Egyptian LPAI H9N2 viruses were genetically and antigenically characterized and compared to representative H9N2 viruses from G1 lineage. Furthermore, the pathogenicity of three genetically distinct Egyptian LPAI H9N2 viruses was assessed by experimental infection in chickens. Whole-genome sequencing revealed that the H9N2 virus of the Egy-2 G1-B lineage (pigeon-like) has become the dominant circulating H9N2 genotype in Egypt since 2016. Considerable variation in virus shedding at day 7 post-infections was detected in infected chickens, but no significant difference in pathogenicity was found between the infected groups. The rapid spread and emergence of new genotypes of the influenza viruses pinpoint the importance of continuous surveillance for the detection of novel reassortant viruses, as well as monitoring the viral evolution.

    Ladda ner fulltext (pdf)
    FULLTEXT01
  • 9.
    Adel, Amany
    et al.
    Agr Res Ctr, Anim Hlth Res Inst, Reference Lab Vet Qual Control Poultry Prod, Giza 12618, Egypt..
    Mohamed, Ahmed Abd Elhalem
    Agr Res Ctr, Anim Hlth Res Inst, Reference Lab Vet Qual Control Poultry Prod, Giza 12618, Egypt..
    Samir, Mahmoud
    Agr Res Ctr, Anim Hlth Res Inst, Reference Lab Vet Qual Control Poultry Prod, Giza 12618, Egypt..
    Hagag, Naglaa M.
    Agr Res Ctr, Anim Hlth Res Inst, Reference Lab Vet Qual Control Poultry Prod, Giza 12618, Egypt..
    Erfan, Ahmed
    Agr Res Ctr, Anim Hlth Res Inst, Reference Lab Vet Qual Control Poultry Prod, Giza 12618, Egypt..
    Said, Mahmoud
    Agr Res Ctr, Anim Hlth Res Inst, Reference Lab Vet Qual Control Poultry Prod, Giza 12618, Egypt..
    Arafa, Abd El Satar
    Agr Res Ctr, Anim Hlth Res Inst, Reference Lab Vet Qual Control Poultry Prod, Giza 12618, Egypt..
    Hassan, Wafaa M. M.
    Agr Res Ctr, Anim Hlth Res Inst, Reference Lab Vet Qual Control Poultry Prod, Giza 12618, Egypt..
    El Zowalaty, Mohamed E.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Shahien, Momtaz A.
    Agr Res Ctr, Anim Hlth Res Inst, Reference Lab Vet Qual Control Poultry Prod, Giza 12618, Egypt..
    Epidemiological and molecular analysis of circulating fowl adenoviruses and emerging of serotypes 1, 3, and 8b in Egypt2021Ingår i: Heliyon, E-ISSN 2405-8440, Vol. 7, nr 12, artikel-id e08366Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Fowl adenoviruses (FAdVs) are a large group of viruses of different serotypes. They are responsible for inclusion body hepatitis, adenoviral gizzard erosion, and hepatitis hydropericardium syndrome. The present study presents a comprehensive overview of FAdVs in Egypt, with a focus on the epidemiological features of virus serotypes across the country. We conducted molecular investigation of multiple FAdV species based on the genetic signature of hypervariable regions 1-4 in the loop1 (L1) region of the hexon gene. Epidemiologically, the Nile Delta governorates showed high positivity of FAdVs, which were more commonly found in broilers than in layers. Genetically, species D and serotype 8a/E dominated, and the findings also revealed the emergence of new FAdV serotypes 1, 3, and 8b. The comparative analysis of hypervariable regions in the L1 region of the hexon gene revealed variables specific to each virus serotype. In silico predictions of L1 region revealed variations in the molecular structure and predicted the antigenic epitopes which may affect the cross-antigenicity between the different FAdV species and serotypes.

    Ladda ner fulltext (pdf)
    FULLTEXT01
  • 10.
    Adler, Marlen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Mechanisms and Dynamics of Carbapenem Resistance in Escherichia coli2014Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The emergence of extended spectrum β-lactamase (ESBL) producing Enterobacteriaceae worldwide has led to an increased use of carbapenems and may drive the development of carbapenem resistance. Existing mechanisms are mainly due to acquired carbapenemases or the combination of ESBL-production and reduced outer membrane permeability. The focus of this thesis was to study the development of carbapenem resistance in Escherichia coli in the presence and absence of acquired β-lactamases. To this end we used the resistance plasmid pUUH239.2 that caused the first major outbreak of ESBL-producing Enterobacteriaceae in Scandinavia.

    Spontaneous carbapenem resistance was strongly favoured by the presence of the ESBL-encoding plasmid and different mutational spectra and resistance levels arose for different carbapenems. Mainly, loss of function mutations in the regulators of porin expression caused reduced influx of antibiotic into the cell and in combination with amplification of β-lactamase genes on the plasmid this led to high resistance levels. We further used a pharmacokinetic model, mimicking antibiotic concentrations found in patients during treatment, to test whether ertapenem resistant populations could be selected even at these concentrations. We found that resistant mutants only arose for the ESBL-producing strain and that an increased dosage of ertapenem could not prevent selection of these resistant subpopulations. In another study we saw that carbapenem resistance can even develop in the absence of ESBL-production. We found mutants in export pumps and the antibiotic targets to give high level resistance albeit with high fitness costs in the absence of antibiotics. In the last study, we used selective amplification of β-lactamases on the pUUH239.2 plasmid by carbapenems to determine the cost and stability of gene amplifications. Using mathematical modelling we determined the likelihood of evolution of new gene functions in this region. The high cost and instability of the amplified state makes de novo evolution very improbable, but constant selection of the amplified state may balance these factors until rare mutations can establish a new function.

    In my studies I observed the influence of β-lactamases on carbapenem resistance and saw that amplification of these genes would further contribute to resistance. The rapid disappearance of amplified arrays of resistance genes in the absence of antibiotic selection may lead to the underestimation of gene amplification as clinical resistance mechanism. Amplification of β-lactamase genes is an important stepping-stone and might lead to the evolution of new resistance genes.

    Delarbeten
    1. Influence of acquired β-lactamases on the evolution of spontaneous carbapenem resistance in Escherichia coli
    Öppna denna publikation i ny flik eller fönster >>Influence of acquired β-lactamases on the evolution of spontaneous carbapenem resistance in Escherichia coli
    2013 (Engelska)Ingår i: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 68, nr 1, s. 51-59Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Objectives: To investigate the influence of plasmid-borne β-lactamases on the evolution of spontaneous carbapenem resistance in Escherichia coli and the fitness costs associated with resistance. Methods: Stepwise selection of carbapenem-resistant mutants with or without the extended-spectrum β-lactamase (ESBL)-encoding plasmid pUUH239.2 was performed. Mutation rates and mutational pathways to resistance were determined. In vitro-selected and constructed mutants were characterized regarding the MICs of the carbapenems, porin expression profiles, growth rates and the presence of mutations in the porins ompC/ompF and their regulatory genes. The influence of the plasmid-encoded β-lactamases TEM-1, OXA-1 and CTX-M-15 on resistance development was determined. Results: Results show that E. coli readily developed reduced carbapenem susceptibility and clinical resistance levels by a combination of porin loss and increased β-lactamase expression, especially towards ertapenem. All tested β-lactamases (CTX-M-15, TEM-1 and OXA-1) contributed to reduced carbapenem susceptibility in the absence of porin expression. However, complete loss of porin expression conferred a 20% fitness cost on the bacterial growth rate. Increased β-lactamase expression through spontaneous gene amplification on the plasmid was a major resistance factor. Conclusions: Plasmid-encoded β-lactamases, including non-ESBL enzymes, have a strong influence on the frequency and resistance level of spontaneous carbapenem-resistant mutants. The fitness cost associated with the loss of OmpC/OmpF in E. coli most likely reduces the survivability of porin mutants and could explain why they have not emerged as a clinical problem in this species.

    Nyckelord
    Fitness cost, Gene amplification, Mutations, Plasmids
    Nationell ämneskategori
    Naturvetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-192026 (URN)10.1093/jac/dks368 (DOI)000312646300010 ()
    Tillgänglig från: 2013-01-24 Skapad: 2013-01-15 Senast uppdaterad: 2017-12-06Bibliografiskt granskad
    2. Frequent emergence of porin-deficient subpopulations with reduced carbapenem susceptibility in ESBL-producing Escherichia coli during exposure to ertapenem in an in vitro pharmacokinetic model
    Öppna denna publikation i ny flik eller fönster >>Frequent emergence of porin-deficient subpopulations with reduced carbapenem susceptibility in ESBL-producing Escherichia coli during exposure to ertapenem in an in vitro pharmacokinetic model
    Visa övriga...
    2013 (Engelska)Ingår i: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 68, nr 6, s. 1319-1326Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    OBJECTIVES:

    Ertapenem resistance is increasing in Enterobacteriaceae. The production of extended-spectrum β-lactamases (ESBLs) and reduced expression of outer membrane porins are major mechanisms of resistance in ertapenem-resistant Klebsiella pneumoniae. Less is known of ertapenem resistance in Escherichia coli. The aim of this study was to explore the impact of ESBL production in E. coli on the antibacterial activity of ertapenem.

    METHODS:

    Two E. coli strains, with and without ESBL production, were exposed to ertapenem in vitro for 48 h at concentrations simulating human pharmacokinetics with conventional and higher dosages.

    RESULTS:

    Isolates with non-susceptibility to ertapenem (MICs 0.75-1.5 mg/L) were detected after five of nine time-kill experiments with the ESBL-producing strain. All of these isolates had ompR mutations, which reduce the expression of outer membrane porins OmpF and OmpC. Higher dosage did not prevent selection of porin-deficient subpopulations. No mutants were detected after experiments with the non-ESBL-producing strain. Compared with other experiments, experiments with ompR mutants detected in endpoint samples showed significantly less bacterial killing after the second dose of ertapenem. Impaired antibacterial activity against E. coli with ESBL production and ompR mutation was also demonstrated in time-kill experiments with static antibiotic concentrations.

    CONCLUSIONS:

    The combination of ESBL production and porin loss in E. coli can result in reduced susceptibility to ertapenem. Porin-deficient subpopulations frequently emerged in ESBL-producing E. coli during exposure to ertapenem at concentrations simulating human pharmacokinetics. Inappropriate use of ertapenem should be avoided to minimize the risk of selection of ESBL-producing bacteria with reduced susceptibility to carbapenems.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-197878 (URN)10.1093/jac/dkt044 (DOI)000319468900016 ()23478794 (PubMedID)
    Tillgänglig från: 2013-04-05 Skapad: 2013-04-05 Senast uppdaterad: 2017-12-06Bibliografiskt granskad
    3. Combinations of mutations in envZ, ftsI, mrdA, acrB and acrR can cause high-level carbapenem resistance in Escherichia coli
    Öppna denna publikation i ny flik eller fönster >>Combinations of mutations in envZ, ftsI, mrdA, acrB and acrR can cause high-level carbapenem resistance in Escherichia coli
    2016 (Engelska)Ingår i: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 71, nr 5, s. 1188-1198Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The worldwide spread of ESBL-producing Enterobacteriaceae has led to an increased use of carbapenems, the group of beta-lactams with the broadest spectrum of activity. Bacterial resistance to carbapenems is mainly due to acquired carbapenemases or a combination of ESBL production and reduced drug influx via loss of outer-membrane porins. Here, we have studied the development of carbapenem resistance in Escherichia coli in the absence of beta-lactamases. We selected mutants with high-level carbapenem resistance through repeated serial passage in the presence of increasing concentrations of meropenem or ertapenem for similar to 60 generations. Isolated clones were whole-genome sequenced, and the order in which the identified mutations arose was determined in the passaged populations. Key mutations were reconstructed, and bacterial growth rates of populations and isolated clones and resistance levels to 23 antibiotics were measured. High-level resistance to carbapenems resulted from a combination of downstream effects of envZ mutation and target mutations in AcrAB-TolC-mediated drug export, together with PBP genes [mrdA (PBP2) after meropenem exposure or ftsI (PBP3) after ertapenem exposure]. Our results show that antibiotic resistance evolution can occur via several parallel pathways and that new mechanisms may appear after the most common pathways (i.e. beta-lactamases and loss of porins) have been eliminated. These findings suggest that strategies to target the most commonly observed resistance mechanisms might be hampered by the appearance of previously unknown parallel pathways to resistance.

    Nationell ämneskategori
    Biokemi och molekylärbiologi Mikrobiologi
    Identifikatorer
    urn:nbn:se:uu:diva-221428 (URN)10.1093/jac/dkv475 (DOI)000376291300008 ()26869688 (PubMedID)
    Forskningsfinansiär
    Forskningsrådet Formas, 2013-5476-25194-9EU, Europeiska forskningsrådet, 282004
    Tillgänglig från: 2014-03-31 Skapad: 2014-03-31 Senast uppdaterad: 2017-12-05Bibliografiskt granskad
    4. High Fitness Costs and Instability of Gene Duplications Reduce Rates of Evolution of New Genes by Duplication-Divergence Mechanisms
    Öppna denna publikation i ny flik eller fönster >>High Fitness Costs and Instability of Gene Duplications Reduce Rates of Evolution of New Genes by Duplication-Divergence Mechanisms
    Visa övriga...
    2014 (Engelska)Ingår i: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 31, nr 6, s. 1526-1535Artikel i tidskrift (Refereegranskat) Published
    Abstract [sv]

    An important mechanism for generation of new genes is by duplication-divergence of existing genes. Duplication-divergence includes several different sub-models, such as subfunctionalization where after accumulation of neutral mutations the original function is distributed between two partially functional and complementary genes, and neofunctionalization where a new function evolves in one of the duplicated copies while the old function is maintained in another copy. The likelihood of these mechanisms depends on the longevity of the duplicated state, which in turn depends on the fitness cost and genetic stability of the duplications. Here, we determined the fitness cost and stability of defined gene duplications/amplifications on a low copy number plasmid. Our experimental results show that the costs of carrying extra gene copies are substantial and that each additional kbp of DNA reduces fitness by approximately 0.15%. Furthermore, gene amplifications are highly unstable and rapidly segregate to lower copy numbers in absence of selection. Mathematical modelling shows that the fitness costs and instability strongly reduces the likelihood of both sub- and neofunctionalization, but that these effects can be off-set by positive selection for novel beneficial functions.

    Nationell ämneskategori
    Mikrobiologi Biokemi och molekylärbiologi Genetik
    Identifikatorer
    urn:nbn:se:uu:diva-221431 (URN)10.1093/molbev/msu111 (DOI)000337067400019 ()
    Tillgänglig från: 2014-03-31 Skapad: 2014-03-31 Senast uppdaterad: 2017-12-05Bibliografiskt granskad
    Ladda ner fulltext (pdf)
    fulltext
    Ladda ner (jpg)
    presentationsbild
  • 11.
    Adler, Marlen
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Anjum, Mehreen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Andersson, Dan I.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Sandegren, Linus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Combinations of mutations in envZ, ftsI, mrdA, acrB and acrR can cause high-level carbapenem resistance in Escherichia coli2016Ingår i: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 71, nr 5, s. 1188-1198Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The worldwide spread of ESBL-producing Enterobacteriaceae has led to an increased use of carbapenems, the group of beta-lactams with the broadest spectrum of activity. Bacterial resistance to carbapenems is mainly due to acquired carbapenemases or a combination of ESBL production and reduced drug influx via loss of outer-membrane porins. Here, we have studied the development of carbapenem resistance in Escherichia coli in the absence of beta-lactamases. We selected mutants with high-level carbapenem resistance through repeated serial passage in the presence of increasing concentrations of meropenem or ertapenem for similar to 60 generations. Isolated clones were whole-genome sequenced, and the order in which the identified mutations arose was determined in the passaged populations. Key mutations were reconstructed, and bacterial growth rates of populations and isolated clones and resistance levels to 23 antibiotics were measured. High-level resistance to carbapenems resulted from a combination of downstream effects of envZ mutation and target mutations in AcrAB-TolC-mediated drug export, together with PBP genes [mrdA (PBP2) after meropenem exposure or ftsI (PBP3) after ertapenem exposure]. Our results show that antibiotic resistance evolution can occur via several parallel pathways and that new mechanisms may appear after the most common pathways (i.e. beta-lactamases and loss of porins) have been eliminated. These findings suggest that strategies to target the most commonly observed resistance mechanisms might be hampered by the appearance of previously unknown parallel pathways to resistance.

  • 12.
    Adler, Marlen
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Anjum, Mehreen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Berg, Otto, G.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräknings- och systembiologi.
    Andersson, Dan I.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Sandegren, Linus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    High Fitness Costs and Instability of Gene Duplications Reduce Rates of Evolution of New Genes by Duplication-Divergence Mechanisms2014Ingår i: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 31, nr 6, s. 1526-1535Artikel i tidskrift (Refereegranskat)
    Abstract [sv]

    An important mechanism for generation of new genes is by duplication-divergence of existing genes. Duplication-divergence includes several different sub-models, such as subfunctionalization where after accumulation of neutral mutations the original function is distributed between two partially functional and complementary genes, and neofunctionalization where a new function evolves in one of the duplicated copies while the old function is maintained in another copy. The likelihood of these mechanisms depends on the longevity of the duplicated state, which in turn depends on the fitness cost and genetic stability of the duplications. Here, we determined the fitness cost and stability of defined gene duplications/amplifications on a low copy number plasmid. Our experimental results show that the costs of carrying extra gene copies are substantial and that each additional kbp of DNA reduces fitness by approximately 0.15%. Furthermore, gene amplifications are highly unstable and rapidly segregate to lower copy numbers in absence of selection. Mathematical modelling shows that the fitness costs and instability strongly reduces the likelihood of both sub- and neofunctionalization, but that these effects can be off-set by positive selection for novel beneficial functions.

  • 13.
    af Klercker, Anna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för biologisk grundutbildning.
    The impact of the ribosomal 16S rRNA modifications on the antibiotic susceptibility and fitness in Escherichia coli  2024Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
    Abstract [en]

    The rRNA molecules which make up the two subunits of the Escherichia coli ribosome are extensively post-transcriptionally modified. The specific purpose of each modification is still unknown. It is proposed that they provide a structure for the ribosomal assembly, which would indicate that they are essential. However, previous literature in this area using E. coli shows that when the modification enzymes are removed individually the effects on growth fitness and antibiotic sensitivity are limited. This makes their role in ribosomal assembly unclear. The effect of removing multiple ribosomal modification enzymes is largely unexplored. The position of many of the modifications are found in clusters, usually in the catalytic domains of the ribosome, which are often targeted by antibiotics, indicating that removing the modification enzymes could affect antibiotic sensitivity. Most of the previous studies on strains with these modification enzymes removed were performed with traditional lambda-red that leaves behind FRT scars, which can cause unwanted spontaneous excisions via recombination between the FRT scars. Here, DIRex lambda-red was used to create clean deletions, which does not produce FRT scars and therefore, allows for more reliable analysis of the ribosomal modification enzymes’ role. The results show that there is a fitness cost and change in antibiotic sensitivity due to multiple of the deletions of the ribosomal modification enzymes. For some of the modifications, this is true when that particular site alone is left unmodified, while for other positions, these effects are only observed when multiple sites are modified simultaneously. For example, the methyltransferase RsmG knockout has a big effect on streptomycin resistance but no fitness cost, while the methyltransferase RsmA and RsmF knockouts causes a fitness cost in combination and causes tetracycline and gentamycin resistance respectively. This indicates that the ribosomal modifications significantly affect the interaction with antibiotics and fitness, and therefore, have a significant part in ribosomal function. 

    Publikationen är tillgänglig i fulltext från 2025-06-12 00:00
  • 14.
    Agongo, Hassanat
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för biologisk grundutbildning.
    Characterization of DNA Methylation in Giardia intestinalis2021Självständigt arbete på avancerad nivå (masterexamen), 40 poäng / 60 hpStudentuppsats (Examensarbete)
    Abstract [en]

    Abstract

    G. intestinalis is an intestinal protozoan parasite that causes 180 million symptomatic diarrheacases (giardiasis) and more than 0.5 billion asymptomatic infections per year. Symptomaticinfections are usually treated with metronidazole (Flagyl). However, resistance is emerging, andan alternative treatment is required. The mechanism to which the parasite causes the disease is notunderstood and, neither is the regulation of encystation (a process where trophozoites differentiateto cyst) However, preliminary data suggest that an epigenetic mechanism is involved. DNAmethylation is an important epigenetic regulator in many organisms, but it is not known if theDNA is methylated in Giardia. The main goal of this project was to characterize DNA methylationin G. intestinalis and, if it exists, study if it is linked to cell differentiation and use it as a target fordrug treatment. We found out using the dot blot technique complemented withimmunofluorescence assays, that 6mA and 5mC DNA methylation exists on the genomic DNA ofthe assemblage A G. intestinalis isolate WB. 6mA methylation was also found on RNA. However,no major differences were detected between trophozoites and cysts. Assemblage B Giardia isolates(GS and H3) also have methylated genomic DNA, but we detected lower levels of methylation. Abioinformatic search was performed in the G. intestinalis WB genome in an attempt to identifyDNA methylases. Expression levels through-out the life cycle, sequence similarities and structuralmodelling using iTASSER identified six putative DNA methylases in the WB genome. The sixDNA methylases were over-expressed in Giardia, three were lethal and three localized to thenucleus. 5-azacytidine and 5-aza-2’-deoxycytidine nucleoside analog drugs prevent methylationand are incorporated into RNA and DNA, respectively. We tested these two drugs on Giardiatrophozoites, and both have effects on the trophozoite stage (IC50 1.46±0.46 μM for 5-aza-2’-deoxycytidine and 111±24 μM for 5-Azacytidine). The 5-aza-2’-deoxycytidine drug is actuallymore effective than metronidazole, showing that nucleoside analogs affecting DNA methylationcould be alternative drugs for treatment of giardiasis.

    Ladda ner fulltext (pdf)
    fulltext
  • 15.
    Ah-King, Malin
    et al.
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Historisk-filosofiska fakulteten, Centrum för genusvetenskap.
    Barron, Andrew B.
    Herberstein, Marie E.
    Genital Evolution: Why Are Females Still Understudied?2014Ingår i: PLoS biology, ISSN 1544-9173, E-ISSN 1545-7885, Vol. 12, nr 5, s. e1001851-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The diversity, variability, and apparent rapid evolution of animal genitalia are a vivid focus of research in evolutionary biology, and studies exploring genitalia have dramatically increased over the past decade. These studies, however, exhibit a strong male bias, which has worsened since 2000, despite the fact that this bias has been explicitly pointed out in the past. Early critics argued that previous investigators too often considered only males and their genitalia, while overlooking female genitalia or physiology. Our analysis of the literature shows that overall this male bias has worsened with time. The degree of bias is not consistent between subdisciplines: studies of the lock-and-key hypothesis have been the most male focused, while studies of cryptic female choice usually consider both sexes. The degree of bias also differed across taxonomic groups, but did not associate with the ease of study of male and female genital characteristics. We argue that the persisting male bias in this field cannot solely be explained by anatomical sex differences influencing accessibility. Rather the bias reflects enduring assumptions about the dominant role of males in sex, and invariant female genitalia. New research highlights how rapidly female genital traits can evolve, and how complex coevolutionary dynamics between males and females can shape genital structures. We argue that understanding genital evolution is hampered by an outdated single-sex bias.

    Ladda ner fulltext (pdf)
    fulltext
  • 16.
    Ahlberg, Per
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Evolutionär organismbiologi.
    Can fossils illuminate the evolution of gnathostome head development?2006Ingår i: European Society for Evolutionary Developmental Biology: The First and Founding Meeting, August 2006, Prague, 2006, s. 363-Konferensbidrag (Övrig (populärvetenskap, debatt, mm))
  • 17.
    Ahlberg, Per
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Evolutionär organismbiologi. Evolutionär organismbiologi.
    CT scanning the nose of Eusthenopteron.2006Ingår i: Journal of Vertebrate Paleontology, ISSN 0272-4634, Vol. 26, nr 3(supplement), s. 35A-Artikel i tidskrift (Övrigt vetenskapligt)
  • 18.
    Ahlberg, Per
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Evolutionär organismbiologi. Evolutionär organismbiologi.
    Fossils, developmental patterning and the origin of tetrapods.2003Ingår i: The new panorama of animal evolution, Pensoft Publishers, Sofia, Bulgaria , 2003, s. 45-54Kapitel i bok, del av antologi (Refereegranskat)
  • 19.
    Ahlberg, Per
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Evolutionär organismbiologi. Evolutionär organismbiologi.
    Clack, Jennifer
    Blom, Henning
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Evolutionär organismbiologi.
    The axial skeleton of the Devonian tetrapod Ichthyostega.2005Ingår i: Nature, ISSN 0028-0836, Vol. 437, nr 7055, s. 137-140Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Ichthyostega was the first Devonian tetrapod to be subject to a whole-body reconstruction and remains, together with Acanthostega one of only two Devonian tetrapods for which near-complete postcranial material is available. It is thus crucially important for our understanding of the earliest stages of tetrapod evolution and terrestrialization. Based on extensive re-examination of original material, augmented by recently collected specimens, we present a new reconstruction of Ichthyostega that differs substantially from those previously published and reveals hitherto unrecognised regionalization in the vertebral column. Ichthyostega is the earliest vertebrate to show obvious adaptations for non-swimming locomotion. Uniquely among early tetrapods, the presacral vertebral column shows pronounced regionalization of neural arch morphology, suggesting that it was adapted for dorsoventral rather than lateral flexion.

  • 20.
    Ahlberg, Per E.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Evolutionär organismbiologi.
    Fossils, developmental patterning and the origin of tetrapods2003Ingår i: The new panorama of animal evolution: Proceedings of the 18th international congress of zoology, Sofia and Moscow: Pensoft Publishers , 2003, s. 44-54Kapitel i bok, del av antologi (Övrigt vetenskapligt)
  • 21.
    Ahlberg, Per
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Evolutionär organismbiologi. Evolutionär organismbiologi.
    Friedman, Matt
    Blom, Henning
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Evolutionär organismbiologi.
    New light on the earliest known tetrapod jaw.2005Ingår i: Journal of Vertebrate Paleontology, ISSN 0272-4634, Vol. 25, nr 3, s. 720-724Artikel i tidskrift (Refereegranskat)
  • 22.
    Ahlberg, Per
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Evolutionär organismbiologi. Evolutionär organismbiologi.
    Köntges, Georgy
    Homologies and cell populations: a response to Sánchez-Villagra and Maier.2006Ingår i: Evolution and Development, ISSN 1520-541X, Vol. 8, s. 116-118Artikel i tidskrift (Övrig (populärvetenskap, debatt, mm))
  • 23.
    Ahlberg, Per
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Evolutionär organismbiologi.
    Smith, Moya
    MRC Centre for Developmental Neurobiology, King's College London, London SE1 1UL, UK.
    Johanson, Zerina
    Department of Biological Sciences and MUCEP, Department of Earth and Planetary Sciences, Macquarie University, Sydney 2010, Australia.
    Developmental plasticity and disparity in early dipnoan (lungfish) dentitions.2006Ingår i: Evolution & Development, ISSN 1520-541X, E-ISSN 1525-142X, Vol. 8, nr 4, s. 331-349Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Although the lungfish (Dipnoi) belong within the Osteichthyes, their dentitions are radically different from other osteichthyans. Lungfish dentitions also show a uniquely high structural disparity during the early evolution of the group, partly owing to the independent variation of odontogenic and odontoclastic processes that are tightly and stereotypically coordinated in other osteichthyans. We present a phylogenetic analysis of early lungfishes incorporating a novel approach to coding these process characters in preference to the resultant adult dental morphology. The results only partially resolve the interrelationships of Devonian dipnoans, but show that the widely discussed hypothesis of separate tooth-plated, dentine-plated, and denticulated lineages is unlikely to be true. The dipnoan status of Diabolepis is corroborated. Lungfish dentitions seem to have undergone extensive and nonparsimonious evolution during the early history of the group, but much of the resulting disparity can be explained by a modest number of evolutionary steps in the underlying developmental processes, those for dental formation (odontogenic) and those for the remodeling of dentine tissue (odontoclastic). Later in lungfish evolution, this disparity was lost as the group settled to a pattern of dental development that is just as stereotypic as, but completely different from, that of other osteichthyans.

  • 24.
    Ahlstrom, Christina A. A.
    et al.
    US Geol Survey, Alaska Sci Ctr, Anchorage, AK 99508 USA..
    Woksepp, Hanna
    Kalmar Cty Reg, Dept Res, Kalmar, Sweden.;Linnaeus Univ, Dept Chem & Biomed Sci, Kalmar, Sweden..
    Sandegren, Linus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Ramey, Andrew M. M.
    US Geol Survey, Alaska Sci Ctr, Anchorage, AK 99508 USA..
    Bonnedahl, Jonas
    Linköping Univ, Dept Biomed & Clin Sci, Linköping, Sweden.;Kalmar Cty Reg, Dept Infect Dis, Kalmar, Sweden..
    Exchange of Carbapenem-Resistant Escherichia coli Sequence Type 38 Intercontinentally and among Wild Bird, Human, and Environmental Niches2023Ingår i: Applied and Environmental Microbiology, ISSN 0099-2240, E-ISSN 1098-5336, Vol. 89, nr 6Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Carbapenem-resistant Enterobacteriaceae (CRE) are a global threat to human health and are increasingly being isolated from nonclinical settings. OXA-48-producing Escherichia coli sequence type 38 (ST38) is the most frequently reported CRE type in wild birds and has been detected in gulls or storks in North America, Europe, Asia, and Africa. The epidemiology and evolution of CRE in wildlife and human niches, however, remains unclear. We compared wild bird origin E. coli ST38 genome sequences generated by our research group and publicly available genomic data derived from other hosts and environments to (i) understand the frequency of intercontinental dispersal of E. coli ST38 clones isolated from wild birds, (ii) more thoroughly measure the genomic relatedness of carbapenem-resistant isolates from gulls sampled in Turkey and Alaska, USA, using long-read whole-genome sequencing and assess the spatial dissemination of this clone among different hosts, and (iii) determine whether ST38 isolates from humans, environmental water, and wild birds have different core or accessory genomes (e.g., antimicrobial resistance genes, virulence genes, plasmids) which might elucidate bacterial or gene exchange among niches. Our results suggest that E. coli ST38 strains, including those resistant to carbapenems, are exchanged between humans and wild birds, rather than separately maintained populations within each niche. Furthermore, despite close genetic similarity among OXA-48-producing E. coli ST38 clones from gulls in Alaska and Turkey, intercontinental dispersal of ST38 clones among wild birds is uncommon. Interventions to mitigate the dissemination of antimicrobial resistance throughout the environment (e.g., as exemplified by the acquisition of carbapenem resistance by birds) may be warranted.

    IMPORTANCE Carbapenem-resistant bacteria are a threat to public health globally and have been found in the environment as well as the clinic. Some bacterial clones are associated with carbapenem resistance genes, such as Escherichia coli sequence type 38 (ST38) and the carbapenemase gene blaOXA-48. This is the most frequently reported carbapenem-resistant clone in wild birds, though it was unclear if it circulated within wild bird populations or was exchanged among other niches. The results from this study suggest that E. coli ST38 strains, including those resistant to carbapenems, are frequently exchanged among wild birds, humans, and the environment. Carbapenem-resistant E. coli ST38 clones in wild birds are likely acquired from the local environment and do not constitute an independent dissemination pathway within wild bird populations. Management actions aimed at preventing the environmental dissemination and acquisition of antimicrobial resistance by wild birds may be warranted.

  • 25.
    Ahlstrom, Christina A.
    et al.
    US Geol Survey, Alaska Sci Ctr, Anchorage, AK 99508 USA.
    Bonnedahl, Jonas
    Linkoping Univ, Dept Clin & Expt Med, SE-58183 Linkoping, Sweden;Kalmar Cty Hosp, Dept Infect Dis, SE-39185 Kalmar, Sweden.
    Woksepp, Hanna
    Kalmar Cty Hosp, Dept Clin Microbiol, SE-39185 Kalmar, Sweden.
    Hernandez, Jorge
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Olsen, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Ramey, Andrew M.
    US Geol Survey, Alaska Sci Ctr, Anchorage, AK 99508 USA.
    Acquisition and dissemination of cephalosporin-resistant E.coli in migratory birds sampled at an Alaska landfill as inferred through genomic analysis2018Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 8, artikel-id 7361Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Antimicrobial resistance (AMR) in bacterial pathogens threatens global health, though the spread of AMR bacteria and AMR genes between humans, animals, and the environment is still largely unknown. Here, we investigated the role of wild birds in the epidemiology of AMR Escherichia coli. Using next-generation sequencing, we characterized cephalosporin-resistant E. coli cultured from sympatric gulls and bald eagles inhabiting a landfill habitat in Alaska to identify genetic determinants conferring AMR, explore potential transmission pathways of AMR bacteria and genes at this site, and investigate how their genetic diversity compares to isolates reported in other taxa. We found genetically diverse E. coli isolates with sequence types previously associated with human infections and resistance genes of clinical importance, including blaCTX-M and blaCMY. Identical resistance profiles were observed in genetically unrelated E. coli isolates from both gulls and bald eagles. Conversely, isolates with indistinguishable core-genomes were found to have different resistance profiles. Our findings support complex epidemiological interactions including bacterial strain sharing between gulls and bald eagles and horizontal gene transfer among E. coli harboured by birds. Results suggest that landfills may serve as a source for AMR acquisition and/or maintenance, including bacterial sequence types and AMR genes relevant to human health.

    Ladda ner fulltext (pdf)
    fulltext
  • 26.
    Ahlstrom, Christina A.
    et al.
    US Geol Survey, Alaska Sci Ctr, 4210 Univ Dr, Anchorage, AK 99508 USA..
    Woksepp, Hanna
    Kalmar Cty Hosp, Dept Dev & Publ Hlth, S-39185 Kalmar, Sweden.;Linnaeus Univ, Dept Med & Optometry, S-39185 Kalmar, Sweden..
    Sandegren, Linus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Mohsin, Mashkoor
    Univ Agr Faisalabad, Inst Microbiol, Faisalabad 38040, Pakistan..
    Hasan, Badrul
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Anim Bacteriol Sect, Anim Bacteriol Sect Microbial Sci Pests & Dis, Bundoora, Vic, Australia..
    Muzyka, Denys
    Inst Expt & Clin Vet Med, Natl Sci Ctr, UA-61023 Kharkiv, Ukraine..
    Hernandez, Jorge
    Kalmar Cty Hosp, Dept Clin Microbiol, SE-39185 Kalmar, Sweden..
    Aguirre, Filip
    Kalmar Cty Hosp, Dept Clin Microbiol, SE-39185 Kalmar, Sweden..
    Tok, Atalay
    Uppsala Univ, Dept Med Sci, Zoonosis Sci Ctr, SE-75185 Uppsala, Sweden..
    Soderman, Jan
    Linköping Univ, Dept Clin & Expt Med, Lab Med, Linköping, Sweden..
    Olsen, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ramey, Andrew M.
    US Geol Survey, Alaska Sci Ctr, 4210 Univ Dr, Anchorage, AK 99508 USA..
    Bonnedahl, Jonas
    Linköping Univ, Dept Biomed & Clin Sci, S-58183 Linköping, Sweden.;Region Kalmar Cty, Dept Infect Dis, S-39185 Kalmar, Sweden..
    Genomically diverse carbapenem resistant Enterobacteriaceae fromwild birds provide insight into global patterns of spatiotemporal dissemination2022Ingår i: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 824, artikel-id 153632Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Carbapenem resistant Enterobacteriaceae (CRE) are a threat to public health globally, yet the role of the environment in the epidemiology of CRE remains elusive. Given that wild birds can acquire CRE, likely from foraging in anthropogenically impacted areas, and may aid in the maintenance and dissemination of CRE in the environment, a spatiotemporal comparison of isolates from different regions and timepoints may be useful for elucidating epidemiological information. Thus, we characterized the genomic diversity of CRE from fecal samples opportunistically collected from gulls (Larus spp.) inhabiting Alaska (USA), Chile, Spain, Turkey, and Ukraine and from black kites (Milvus migrans) sampled in Pakistan and assessed evidence for spatiotemporal patterns of dissemination. Within and among sampling locations, a high diversity of carbapenemases was found, including Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-beta-lactamase (NDM), oxacillinase (OXA), and Verona integron Metallo beta-lactamase (VIM). Although the majority of genomic comparisons among samples did not provide evidence for spatial dissemination, we did find strong evidence for dissemination among Alaska, Spain, and Turkey. We also found strong evidence for temporal dissemination among samples collected in Alaska and Pakistan, though the majority of CRE clones were transitory and were not repeatedly detected among locations where samples were collected longitudinally. Carbapenemase-producing hypervirulent K. pneumoniae was isolated from gulls in Spain and Ukraine and some isolates harbored antimicrobial resistance genes conferring resistance to up to 10 different antibiotic classes, including colistin. Our results are consistent with local acquisition of CRE by wild birds with spatial dissemination influenced by intermediary transmission routes, likely involving humans. Furthermore, our results support the premise that anthropogenicallyassociated wild birds may be good sentinels for understanding the burden of clinically-relevant antimicrobial resistance in the local human population.

    Ladda ner fulltext (pdf)
    fulltext
  • 27.
    Ahlström, Anna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för biologisk grundutbildning.
    Testing the specificity of the pBAD arabinose reporter2017Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
    Abstract [en]

    The project highlights Salmonella enterica subspecies enterica serovar Typhimurium (S. Tm)'s ability to metabolize simple sugars released from dead commensal bacteria, by using the pBAD (araBAD promoter) system as a reporter of L-arabinose availability. Using bioinformatics and homology of conserved L-arabinose transporter genes shared in Escherichia coli K12 (E. coli) and S. Tm, we aimed to create a S. Tm mutant strain unable to obtain L-arabinose from it environment. During the projects course of time it was discovered that L-arabinose transporters are not a shared gene trait between E. coli and S. Tm, and that putative L-arabinose transporter orthologues may exists in the S. Tm genome.

    Ladda ner fulltext (pdf)
    fulltext
  • 28.
    Ahmed Osman, Omneya
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Limnologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Beier, Sara
    Leibniz Inst Balt Sea Res, Warnemunde, Germany..
    Grabherr, Manfred
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Bertilsson, Stefan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Limnologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Interactions of Freshwater Cyanobacteria with Bacterial Antagonists2017Ingår i: Applied and Environmental Microbiology, ISSN 0099-2240, E-ISSN 1098-5336, Vol. 83, nr 7, artikel-id UNSP e02634Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cyanobacterial and algal mass development, or blooms, have severe effects on freshwater and marine systems around the world. Many of these phototrophs produce a variety of potent toxins, contribute to oxygen depletion, and affect water quality in several ways. Coexisting antagonists, such as cyanolytic bacteria, hold the potential to suppress, or even terminate, such blooms, yet the nature of this interaction is not well studied. We isolated 31 cyanolytic bacteria affiliated with the genera Pseudomonas, Stenotrophomonas, Acinetobacter, and Delftia from three eutrophic freshwater lakes in Sweden and selected four phylogenetically diverse bacterial strains with strong-to-moderate lytic activity. To characterize their functional responses to the presence of cyanobacteria, we performed RNA sequencing (RNA-Seq) experiments on coculture incubations, with an initial predator-prey ratio of 1: 1. Genes involved in central cellular pathways, stress-related heat or cold shock proteins, and antitoxin genes were highly expressed in both heterotrophs and cyanobacteria. Heterotrophs in coculture expressed genes involved in cell motility, signal transduction, and putative lytic activity. L, D-Transpeptidase was the only significantly upregulated lytic gene in Stenotrophomonas rhizophila EK20. Heterotrophs also shifted their central metabolism from the tricarboxylic acid cycle to the glyoxylate shunt. Concurrently, cyanobacteria clearly show contrasting antagonistic interactions with the four tested heterotrophic strains, which is also reflected in the physical attachment to their cells. In conclusion, antagonistic interactions with cyanobacteria were initiated within 24 h, and expression profiles suggest varied responses for the different cyanobacteria and studied cyanolytes. IMPORTANCE Here, we present how gene expression profiles can be used to reveal interactions between bloom-forming freshwater cyanobacteria and antagonistic heterotrophic bacteria. Species-specific responses in both heterotrophs and cyanobacteria were identified. The study contributes to a better understanding of the interspecies cellular interactions underpinning the persistence and collapse of cyanobacterial blooms.

    Ladda ner fulltext (pdf)
    fulltext
  • 29.
    Ainhoa, Moliner Morro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Microbiology, Tumour and Cell Biology Department, Karolinska Institutet.
    Depicting the role of CD2AP during Old World alphavirus infection2017Självständigt arbete på avancerad nivå (masterexamen), 30 poäng / 45 hpStudentuppsats (Examensarbete)
    Ladda ner fulltext (pdf)
    fulltext
  • 30.
    Akaberi, Dario
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Identification of protease inhibitors against Flaviviruses and Coronaviruses2023Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Vector-borne flaviviruses and coronaviruses of zoonotic origins are important human pathogens and represent a serious threat to public health worldwide. Flaviviruses can be found on all continents, apart from Antarctica, where they are transmitted by arthropod vectors causing millions of infections every year. While most of the infections are mild or asymptomatic, flaviviruses like dengue and yellow fever viruses can cause potentially lethal hemorrhagic fever and shock syndrome. Neurotropic flaviviruses like West Nile, Japanese encephalitis, and Tick-borne encephalitis (TBEV) can cause meningoencephalitis with long-term symptoms.  Coronaviruses, and in particular betacoronaviruses of zoonotic origin like SARS (2003) and MERS (2012), have been periodically emerging since the early 2000s causing outbreaks of severe respiratory syndrome. The latest example is SARS-CoV-2 that after causing a cluster of infection in the Chinese city of Wuhan, spread all over the world causing at present over 6.9 million deaths. Although vaccines are essential in preventing infections or severe disease and hospitalization in the case of SARS-CoV-2, antivirals represent an extremely valuable tool for treatment and prevention of current and future flavivirus and coronavirus infections. In the work presented in this thesis we have used a combination of in silico and in vitro techniques to identify and test the activity of potential inhibitors of viral proteases. 

    In our first study (paper 1) we unexpectedly identified an HIV protease inhibitor with in vitro activity against ZIKV NS2B-NS3 protease. The inhibitor was identified by virtual screening of a library of known protease inhibitors, evaluated by molecular dynamics simulation and finally tested against recombinant ZIKV protease using a FRET-based enzymatic assay. The same combination of molecular docking and molecular dynamics simulations were also used to correctly predict the activity of a known pan-Flavivirus protease inhibitor against TBEV protease (paper 2). As a result, we were the first to report peptide-based compounds with in vitro activity against TBEV. 

    After the outbreak of the COVID-19 we switched our attention to SARS-CoV-2. We first tested the inhibitory effect of the broad-spectrum antiviral nitric oxide (NO) and found that the NO-releasing compound SNAP had a dose dependent inhibitory effect on SARS-CoV-2 replication in cell-based assays (paper 3). We speculated that SNAP could inhibit SARS-COV-2 protease by trans-nitration of the catalytic Cys145 of SARS-CoV-2 main protease and found that SNAP had a dose dependent inhibitory effect on recombinant SARS-CoV-2 Mpro protease activity in an in vitro enzymatic assay. In our last study (paper 4) we identified a new class of potent SARS-CoV-2 protease inhibitors through the affinity screening of DNA-encoded-chemical libraries containing 4.2 billion compounds. The identified compounds inhibited recombinant SARS-CoV-2 protease with IC50 as low as 25 nM and had a dose dependent antiviral effect in the low micromolar range in infected Calu-3 and Caco-2 cell lines. 

    Delarbeten
    1. Targeting the NS2B-NS3 protease of tick-borne encephalitis virus with pan-flaviviral protease inhibitors
    Öppna denna publikation i ny flik eller fönster >>Targeting the NS2B-NS3 protease of tick-borne encephalitis virus with pan-flaviviral protease inhibitors
    Visa övriga...
    2021 (Engelska)Ingår i: Antiviral Research, ISSN 0166-3542, E-ISSN 1872-9096, Vol. 190, artikel-id 105074Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Tick-borne encephalitis (TBE) is a severe neurological disorder caused by tick-borne encephalitis virus (TBEV), a member of the Flavivirus genus. Currently, two vaccines are available in Europe against TBEV. However, TBE cases have been rising in Sweden for the past twenty years, and thousands of cases are reported in Europe, emphasizing the need for antiviral treatments against this virus. The NS2B-NS3 protease is essential for flaviviral life cycle and has been studied as a target for the design of inhibitors against several well-known flaviviruses, but not TBEV. In the present study, Compound 86, a known tripeptidic inhibitor of dengue (DENV), West Nile (WNV) and Zika (ZIKV) proteases, was predicted to be active against TBEV protease using a combination of in silico techniques. Further, Compound 86 was found to inhibit recombinant TBEV protease with an IC50 = 0.92 mu M in the in vitro enzymatic assay. Additionally, two more peptidic analogues were synthetized and they displayed inhibitory activities against both TBEV and ZIKV proteases. In particular, Compound 104 inhibited ZIKV protease with an IC50 = 0.25 mu M. These compounds represent the first reported inhibitors of TBEV protease to date and provides valuable information for the further development of TBEV as well as pan-flavivirus protease inhibitors.

    Ort, förlag, år, upplaga, sidor
    ElsevierELSEVIER, 2021
    Nyckelord
    Tick-borne encephalitis virus, Zika virus, NS2B-NS3 serine protease, Docking, MD simulations, Peptide hybrids
    Nationell ämneskategori
    Infektionsmedicin
    Identifikatorer
    urn:nbn:se:uu:diva-447918 (URN)10.1016/j.antiviral.2021.105074 (DOI)000657783600004 ()33872674 (PubMedID)
    Forskningsfinansiär
    Swedish National Infrastructure for Computing (SNIC), SNIC 2017/1-213Swedish National Infrastructure for Computing (SNIC), SNIC 2018/3-252Swedish National Infrastructure for Computing (SNIC), SNIC 2019/3-312
    Tillgänglig från: 2021-09-02 Skapad: 2021-09-02 Senast uppdaterad: 2024-01-15Bibliografiskt granskad
    2. Identification of a C2-symmetric diol based human immunodeficiency virus protease inhibitor targeting Zika virus NS2B-NS3 protease
    Öppna denna publikation i ny flik eller fönster >>Identification of a C2-symmetric diol based human immunodeficiency virus protease inhibitor targeting Zika virus NS2B-NS3 protease
    Visa övriga...
    2020 (Engelska)Ingår i: Journal of Biomolecular Structure and Dynamics, ISSN 0739-1102, E-ISSN 1538-0254, Vol. 38, nr 18, s. 5526-5536Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Zika virus (ZIKV) is an emerging mosquito-borne flavivirus and infection by ZIKV Asian lineage is known to cause fetal brain anomalies and Guillain-Barrés syndrome. The WHO declared ZIKV a global public health emergency in 2016. However, currently neither vaccines nor antiviral prophylaxis/treatments are available. In this study, we report the identification of a C2-symmetric diol-based Human immunodeficiency virus type-1 (HIV) protease inhibitor active against ZIKV NS2B-NS3 protease. The compound, referred to as 9b, was identified by in silico screening of a library of 6265 protease inhibitors. Molecular dynamics (MD) simulation studies revealed that compound 9b formed a stable complex with ZIKV protease. Interaction analysis of compound 9b's binding pose from the cluster analysis of MD simulations trajectories predicted that 9b mostly interacted with ZIKV NS3. Although designed as an aspartyl protease inhibitor, compound 9b was found to inhibit ZIKV serine protease in vitro with IC50 = 143.25 ± 5.45 µM, in line with the in silico results. Additionally, linear interaction energy method (LIE) was used to estimate binding affinities of compounds 9b and 86 (a known panflavivirus peptide hybrid with IC50 = 1.64 ± 0.015 µM against ZIKV protease). The LIE method correctly predicted the binding affinity of compound 86 to be lower than that of 9b, proving to be superior to the molecular docking methods in scoring and ranking compounds. Since most of the reported ZIKV protease inhibitors are positively charged peptide-hybrids, with our without electrophilic warheads, compound 9b represents a less polar and more drug-like non-peptide hit compound useful for further optimization.Communicated by Ramaswamy Sarma.

    Nyckelord
    In silico screening, NS2B-NS3 protease, Zika virus (ZIKV), protease inhibitors, structure-based drug discovery
    Nationell ämneskategori
    Läkemedelskemi
    Identifikatorer
    urn:nbn:se:uu:diva-430553 (URN)10.1080/07391102.2019.1704882 (DOI)000504558200001 ()31880199 (PubMedID)
    Forskningsfinansiär
    Kjell och Märta Beijers Stiftelse
    Tillgänglig från: 2021-01-11 Skapad: 2021-01-11 Senast uppdaterad: 2023-08-10Bibliografiskt granskad
    3. Mitigation of the replication of SARS-CoV-2 by nitric oxide in vitro
    Öppna denna publikation i ny flik eller fönster >>Mitigation of the replication of SARS-CoV-2 by nitric oxide in vitro
    Visa övriga...
    2020 (Engelska)Ingår i: Redox Biology, E-ISSN 2213-2317, Vol. 37, artikel-id 101734Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The ongoing SARS-CoV-2 pandemic is a global public health emergency posing a high burden on nations' health care systems and economies. Despite the great effort put in the development of vaccines and specific treatments, no prophylaxis or effective therapeutics are currently available. Nitric oxide (NO) is a broad-spectrum antimicrobial and a potent vasodilator that has proved to be effective in reducing SARS-CoV replication and hypoxia in patients with severe acute respiratory syndrome. Given the potential of NO as treatment for SARS-CoV-2 infection, we have evaluated the in vitro antiviral effect of NO on SARS-CoV-2 replication. The NO-donor S-nitroso-N-acetylpenicillamine (SNAP) had a dose dependent inhibitory effect on SARS-CoV-2 replication, while the non S-nitrosated NAP was not active, as expected. Although the viral replication was not completely abolished (at 200 μM and 400 μM), SNAP delayed or completely prevented the development of viral cytopathic effect in treated cells, and the observed protective effect correlated with the level of inhibition of the viral replication. The capacity of the NO released from SNAP to covalently bind and inhibit SARS-CoV-2 3CL recombinant protease in vitro was also tested. The observed reduction in SARS-CoV-2 protease activity was consistent with S-nitrosation of the enzyme active site cysteine.

    Ort, förlag, år, upplaga, sidor
    Elsevier, 2020
    Nyckelord
    3CL protease, COVID-19, FRET, Nitric oxide, SARS-CoV-2
    Nationell ämneskategori
    Infektionsmedicin
    Identifikatorer
    urn:nbn:se:uu:diva-430554 (URN)10.1016/j.redox.2020.101734 (DOI)000605007700001 ()33007504 (PubMedID)
    Forskningsfinansiär
    Vetenskapsrådet, 2017-05807Vetenskapsrådet, 2018-02569Knut och Alice Wallenbergs StiftelseScience for Life Laboratory, SciLifeLab
    Tillgänglig från: 2021-01-11 Skapad: 2021-01-11 Senast uppdaterad: 2024-01-04Bibliografiskt granskad
    4. Identification of unique and potent inhibitors of SARS-CoV-2 main protease from DNA-encoded chemical libraries
    Öppna denna publikation i ny flik eller fönster >>Identification of unique and potent inhibitors of SARS-CoV-2 main protease from DNA-encoded chemical libraries
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nyckelord
    SARS-CoV-2, antivirals, protease inhibitors
    Nationell ämneskategori
    Infektionsmedicin Läkemedelskemi
    Forskningsämne
    Biologi med inriktning mot mikrobiologi
    Identifikatorer
    urn:nbn:se:uu:diva-508906 (URN)
    Tillgänglig från: 2023-08-10 Skapad: 2023-08-10 Senast uppdaterad: 2023-08-14Bibliografiskt granskad
    Ladda ner fulltext (pdf)
    UUThesis_D-Akaberi-2023
    Ladda ner (jpg)
    preview image
  • 31.
    Akula, Srinivas
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Hellman, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    The Appearance and Diversification of Receptors for IgM During Vertebrate Evolution2017Ingår i: IGM AND ITS RECEPTORS AND BINDING PROTEINS / [ed] Kubagawa, H Burrows, PD, SPRINGER-VERLAG BERLIN , 2017, s. 1-23Kapitel i bok, del av antologi (Refereegranskat)
    Abstract [en]

    Three different receptors that interact with the constant domains of IgM have been identified: the polymeric immunoglobulin (Ig) receptor (PIGR), the dual receptor for IgA/IgM (Fc alpha mu R) and the IgM receptor (Fc mu R). All of them are related in structure and located in the same chromosomal region in mammals. The functions of the PIGRs are to transport IgM and IgA into the intestinal lumen and to saliva and tears, whereas the Fc alpha mu Rs enhance uptake of immune complexes and antibody coated bacteria and viruses by B220+ B cells and phagocytes, as well as dampening the Ig response to thymus-independent antigens. The Fc mu Rs have broad-spectrum effects on B-cell development including effects on IgM homeostasis, B-cell survival, humoral immune responses and also in autoantibody formation. The PIGR is the first of these receptors to appear during vertebrate evolution and is found in bony fish and all tetrapods but not in cartilaginous fish. The Fc mu R is present in all extant mammalian lineages and also in the Chinese and American alligators, suggesting its appearance with early reptiles. Currently the Fc alpha mu R has only been found in mammals and is most likely the evolutionary youngest of the three receptors. In bony fish, the PIGR has either 2, 3, 4, 5 or 6 extracellular Ig-like domains, whereas in amphibians, reptiles and birds it has 4 domains, and 5 in all mammals. The increase in domain number from 4 to 5 in mammals has been proposed to enhance the interaction with IgA. Both the Fc alpha mu Rs and the Fc mu Rs contain only one Ig domain; the domain that confers Ig binding. In both of these receptors this domain shows the highest degree of sequence similarity to domain 1 of the PIGR. All Ig domains of these three receptors are V type domains, indicating they all have the same origin although they have diversified extensively in function during vertebrate evolution by changing expression patterns and cytoplasmic signaling motifs.

  • 32.
    Alam, Shanzida Binte
    et al.
    Bangladesh Agr Univ, Dept Microbiol & Hyg, Mymensingh 2202, Bangladesh.
    Mahmud, Muket
    Bangladesh Agr Univ, Dept Microbiol & Hyg, Mymensingh 2202, Bangladesh.
    Akter, Rafiya
    Bangladesh Agr Univ, Dept Microbiol & Hyg, Mymensingh 2202, Bangladesh.
    Hasan, Mahadi
    Bangladesh Agr Univ, Dept Microbiol & Hyg, Mymensingh 2202, Bangladesh.
    Sobur, Abdus
    Bangladesh Agr Univ, Dept Microbiol & Hyg, Mymensingh 2202, Bangladesh.
    Nazir, K. H. M. Nazmul Hussain
    Bangladesh Agr Univ, Dept Microbiol & Hyg, Mymensingh 2202, Bangladesh.
    Noreddin, Ayman
    Univ Calif Irvine, Irvine, CA 92697 USA;Univ Sharjah, Sharjah Med Res Inst, Infect Dis & Antiinfect Therapy Res Grp, Sharjah 27272, U Arab Emirates;Univ Sharjah, Coll Pharm, Sharjah 27272, U Arab Emirates.
    Rahman, Tanvir
    Bangladesh Agr Univ, Dept Microbiol & Hyg, Mymensingh 2202, Bangladesh.
    El Zowalaty, Mohamed E.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Univ Sharjah, Sharjah Med Res Inst, Infect Dis & Antiinfect Therapy Res Grp, Sharjah 27272, U Arab Emirates;Univ Sharjah, Coll Pharm, Sharjah 27272, U Arab Emirates.
    Rahman, Marzia
    Bangladesh Agr Univ, Dept Microbiol & Hyg, Mymensingh 2202, Bangladesh.
    Molecular Detection of Multidrug Resistant Salmonella Species Isolated from Broiler Farm in Bangladesh2020Ingår i: Pathogens, E-ISSN 2076-0817, Vol. 9, nr 3, artikel-id 201Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Multidrug resistant (MDR) Salmonella are a leading cause of foodborne diseases and serious human health concerns worldwide. In this study we detected MDR Salmonella in broiler chicken along with the resistance genes and class 1 integron gene intl1. A total of 100 samples were collected from broiler farms comprising 50 cloacal swabs, 35 litter and 15 feed samples. Overall prevalence of Salmonella was 35% with the highest detected in cloacal swabs. Among the Salmonella, 30 isolates were confirmed as S. enterica serovar Typhimurium using molecular methods of PCR. Disk diffusion susceptibility test revealed that all the Salmonella were classified as MDR with the highest resistance to tetracycline (97.14%), chloramphenicol (94.28%), ampicillin (82.85%) and streptomycin (77.14%). The most prevalent resistance genotypes were tetA (97.14%), floR (94.28%), blaTEM-1 (82.85%) and aadA1 (77.14%). In addition, among the MDR Salmonella, 20% were positive for class 1 integron gene (intl1). As far as we know, this is the first study describing the molecular basis of antibiotic resistance in MDR Salmonella from broiler farms in Bangladesh. In addition to tetA, floR, blaTEM-1, aadA1 and intl1 were also detected in the isolated MDR Salmonella. The detection of MDR Salmonella in broiler chicken carrying intl1 is of serious public health concern because of their zoonotic nature and possibilities to enter into the food chain.

    Ladda ner fulltext (pdf)
    FULLTEXT01
  • 33.
    Albrecht, Lisa M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Antibiotic Resistance: Selection in the Presence of Metals and Antimicrobials2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The external environment is complex: Antibiotics, metals and antimicrobials do not exist in isolation but in mixtures. Human activities such as animal husbandry, fertilization of agricultural fields and human medicine release high amounts these compounds into the environment. The work in this thesis contributes to our understanding of how the selection of bacterial antibiotic resistance can be facilitated by the pollution by metals and antimicrobials. We show that low levels of antibiotics, metals and combinations thereof can lead to the selection of chromosomally encoded antibiotic resistance genes as well as a multidrug resistance plasmid. The underlying genetic and cellular mechanisms of selection identified relate to mutational changes in a plasmid-encoded metal resistance operon, and metal-associated increases in cellular membrane permeability. We further show that exposure to quaternary ammonium compounds can result in cross-resistance to antibiotics following genetic changes in genes related to efflux, membrane synthesis and transcription/translation. Taken together, the work in this thesis suggests that the stewardship of antibiotics should include prudent use of metals and antimicrobials. 

    Delarbeten
    1. Selection of a multidrug resistance plasmid by sublethal levels of antibiotics and heavy metals
    Öppna denna publikation i ny flik eller fönster >>Selection of a multidrug resistance plasmid by sublethal levels of antibiotics and heavy metals
    Visa övriga...
    2014 (Engelska)Ingår i: mBio, ISSN 2161-2129, E-ISSN 2150-7511, Vol. 5, nr 5, s. e01918-14-Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    How sublethal levels of antibiotics and heavy metals select for clinically important multidrug resistance plasmids is largely unknown. Carriage of plasmids generally confers substantial fitness costs, implying that for the plasmid-carrying bacteria to be maintained in the population, the plasmid cost needs to be balanced by a selective pressure conferred by, for example, antibiotics or heavy metals. We studied the effects of low levels of antibiotics and heavy metals on the selective maintenance of a 220-kbp extended-spectrum β-lactamase (ESBL) plasmid identified in a hospital outbreak of Klebsiella pneumoniae and Escherichia coli. The concentrations of antibiotics and heavy metals required to maintain plasmid-carrying bacteria, the minimal selective concentrations (MSCs), were in all cases below (almost up to 140-fold) the MIC of the plasmid-free susceptible bacteria. This finding indicates that the very low antibiotic and heavy metal levels found in polluted environments and in treated humans and animals might be sufficiently high to maintain multiresistance plasmids. When resistance genes were moved from the plasmid to the chromosome, the MSC decreased, showing that MSC for a specific resistance conditionally depends on genetic context. This finding suggests that a cost-free resistance could be maintained in a population by an infinitesimally low concentration of antibiotic. By studying the effect of combinations of several compounds, it was observed that for certain combinations of drugs each new compound added lowered the minimal selective concentration of the others. This combination effect could be a significant factor in the selection of multidrug resistance plasmids/bacterial clones in complex multidrug environments.

    IMPORTANCE: Antibiotic resistance is in many pathogenic bacteria caused by genes that are carried on large conjugative plasmids. These plasmids typically contain multiple antibiotic resistance genes as well as genes that confer resistance to biocides and heavy metals. In this report, we show that very low concentrations of single antibiotics and heavy metals or combinations of compounds can select for a large plasmid that carries resistance to aminoglycosides, β-lactams, tetracycline, macrolides, trimethoprim, sulfonamide, silver, copper, and arsenic. Our findings suggest that the low levels of antibiotics and heavy metals present in polluted external environments and in treated animals and humans could allow for selection and enrichment of bacteria with multiresistance plasmids and thereby contribute to the emergence, maintenance, and transmission of antibiotic-resistant disease-causing bacteria.

    Nationell ämneskategori
    Mikrobiologi inom det medicinska området
    Forskningsämne
    Mikrobiologi; Molekylär genetik
    Identifikatorer
    urn:nbn:se:uu:diva-235222 (URN)10.1128/mBio.01918-14 (DOI)000345459000067 ()25293762 (PubMedID)
    Tillgänglig från: 2014-10-29 Skapad: 2014-10-29 Senast uppdaterad: 2018-08-10Bibliografiskt granskad
    2. Mutation in the Copper-Induced sil Operon Enables High-Level Silver Resistance and Silver Facilitated Co-Selection of Multidrug Resistance Plasmid
    Öppna denna publikation i ny flik eller fönster >>Mutation in the Copper-Induced sil Operon Enables High-Level Silver Resistance and Silver Facilitated Co-Selection of Multidrug Resistance Plasmid
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Human activities are responsible for an accumulation of metals in health care and agricultural environments, and plasmid-encoded metal tolerance operons enable bacteria to rapidly adapt to metal exposure under such conditions. While the mechanisms of action of many metal resistance systems have been described, there is still limited understanding of their role in co-selection of antibiotic resistance in metal-containing environments. Whether plasmid-encoded metal resistance genes confer significant selective advantages is of interest as it has implications for plasmid enrichment and the spread of plasmid-borne antibiotic resistance genes. To increase our understanding of plasmid-mediated metal resistance, we studied the sil operon and its phenotypes in E. coli during growth in the absence and presence of silver and copper. We found that the sil operon provides resistance to both silver and copper. However, it is induced by copper only, and constitutive expression due to point mutations in the two-component silS gene provides high-level silver resistance. Furthermore, we showed that a high-level silver resistant mutant could be enriched in the presence of silver. This enrichment entailed co-selection of the multidrug resistance plasmid pUUH239.2. Our results show that a copper resistance operon can provide high-level silver resistance following a single point mutation, and that the silver resistance phenotype subsequently can co-select for antibiotic resistance in the presence of silver. 

    Nationell ämneskategori
    Övrig annan medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-356961 (URN)
    Tillgänglig från: 2018-08-09 Skapad: 2018-08-09 Senast uppdaterad: 2018-08-10
    3. Potentiation of the Selective Effect of Antibiotics by Metal Ions
    Öppna denna publikation i ny flik eller fönster >>Potentiation of the Selective Effect of Antibiotics by Metal Ions
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Complex mixtures of antibiotics and metals are present in many environments ranging from municipal sewage to irrigation water and manure used as agricultural fertilizer. Such mixtures of drugs and metals exert unique selection pressures on local bacterial communities and could function as hotspots for enrichment of antibiotic resistance genes. The presence of metals in the environment has previously been linked to increases in tolerance to antibiotics. In this study, we investigated metal-potentiated selection of antibiotic resistant Salmonella enterica strains. Six environmentally relevant metals were examined in combinations with three different antibiotics. By performing competitions between an antibiotic resistant mutant and the isogenic wild type in each metal-antibiotic combination, we assessed the minimal selective concentration (MSC) of the antibiotic for the resistant strain. The metals silver, cadmium and mercury all exhibited potentiating effects, reducing the MSC of the antibiotic up to 5-fold as compared to in the absence of the metal. We further show that the potentiating metals increased permeability of the cellular outer membrane. These results demonstrate that the presence of a metal can decrease the concentration of an antibiotic required to select for an antibiotic resistant strain, and they indicate that this process involves metal-facilitated uptake of the antibiotic following damage to the outer membrane.

    Nyckelord
    Antibiotic resistance, Selection
    Nationell ämneskategori
    Övrig annan medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-356966 (URN)
    Tillgänglig från: 2018-08-09 Skapad: 2018-08-09 Senast uppdaterad: 2018-08-10
    4. Cross-Resistance to Antibiotics After Exposure to Qaternary Ammonium Compounds
    Öppna denna publikation i ny flik eller fönster >>Cross-Resistance to Antibiotics After Exposure to Qaternary Ammonium Compounds
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Quaternary ammonium compounds (QACs) are common antimicrobials that are used in a variety of consumer products, such as lotions, sunscreen, hair conditioners and hand sanitizers, to inhibit bacterial growth. However, it has been noted that bacteria exposed to QACs can develop resistance, and additionally, resistance to QACs has been observed to provide cross-resistance to antibiotics. In order to identify genetic adaptations for this resistance pattern, we exposed E. coli to three different QACs at sub-MIC and above-MIC concentrations, and identified genetic changes by whole genome sequencing. We found that initial adaptation, at sub-MIC levels, happened through efflux mechanisms, and that subsequent genetic changes, during above-MIC exposure, involved genes associated with the cell membranes and with transcription/translation. We also found that these genetic changes provided cross-resistance to other QACs as well as to several antibiotics.

    Nyckelord
    Antibiotic resistance, Antimicrobials, Cross-resistance
    Nationell ämneskategori
    Övrig annan medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-356967 (URN)
    Tillgänglig från: 2018-08-09 Skapad: 2018-08-09 Senast uppdaterad: 2018-08-10
    Ladda ner fulltext (pdf)
    fulltext
    Ladda ner (jpg)
    presentationsbild
  • 34. Ali El Hadi Mohamed, Rania
    et al.
    Abdelgadir, Deena M.
    Bashab, Hind M.
    Al-Shuraym, Laila A.
    Sfouq Aleanizy, Fadilah
    Alqahtani, Fulwah Y.
    Ahmed Al-Keridis, Lamya
    Mohamed, Nahla
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Limnologi. Princess Nourah Bint Abdurrahman University.
    First record of West Nile Virus detection inside wild mosquitoes in Khartoum capital of Sudan using PCR2020Ingår i: Saudi Journal of Biological Sciences, ISSN 1319-562X, Vol. 27, nr 12, s. 3359-3364Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study aimed to explore the presence of West Nile Virus (WNV) inside four species of mosquitoes: Culex univittatus (Theobald), Culex quinquefasciatus (Say) Aedes vittatus (Bigot) and Aedes vexans (Meigen). Adult wild mosquitoes were collected from different sites: Soba West, Hellat Kuku, Shambat, and Khartoum North Central Live Stock Market (KCLM). Surveys were carried out at Khartoum State during two phases: pre to the rainy season and post to the rainy season. Mosquito specimens were identified using classical keys then preserved at −80 °C freezer for two weeks till the virus examination using polymerase chain reaction (PCR) were carried out. WNV has been detected inside the three species of mosquitoes: A. vexans, C. univittatus, and C. quinquefasciatus. The species were collected from Hellat Kuku, (Shambat and Hellat Kuku), and (Shambat and KCLM) respectively. Two species of mosquitoes were positive for the virus: C. quinquefasciatus and C. univittatus. Positive results for the virus during the first phase of the study; males of C. quinquefasciatus and C. univittatus collected during the second phase of the study were also tested for the existence of the virus and they were positive. For our knowledge this study represents first record of WNV inside wild mosquitoes in Sudan. PCR technique provided reliable information because specific primer-probe sets were used for the detection of the virus. Extra studies are required to incriminate these species of mosquitoes as potential vectors of WNV.

    Ladda ner fulltext (pdf)
    fulltext
  • 35.
    Ali, M. Z.
    et al.
    BLRI, Anim Hlth Res Div, Dhaka 1341, Bangladesh.
    Hasan, Badrul
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Follow Up of Maternally Derived Antibodies Titer against Economically Important Viral Diseases of Chicken2018Ingår i: POULTRY SCIENCE JOURNAL, ISSN 2345-6604, Vol. 6, nr 2, s. 149-154Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The study was conducted to know the rate of maternally derived antibodies (MDAs) transfer from parents to their offspring and declining the MDAs in their chicks at 0, 7, 14, and 21 days of age against four major poultry viruses like Newcastle disease virus (NDV), Infectious bronchitis virus (IBV), Infectious bursal diseases virus (IBDV), and Avian Reo virus (ARV). The MDAs was studied on Grandparent (GP) to Parent stock (PS), and Parent stock (PS) to broiler at 30 weeks and 50 weeks of age in Cobb-500 broiler strain chicken. The MDAs was measured from serum antibody titer by indirect ELISA test. The MDAs transfer rate against NDV from GP to PS at 50 weeks of age was higher (68.82%) than at 30 weeks of age but in case of PS to broiler it was higher (66.01%) at 30 weeks of age and its persistent rate also higher (7.96%) up to 21th days of age. Against IBV, MDAs transfer rates were higher in PS to broiler than GP to PS of both ages and highest rates were revealed in PS to broiler at 30 weeks of age as 70.72%. On the other hand, among all lines MDAs transfer rates against IBDV was higher (86.94%) in GP to PS at 30 weeks of age. For ARV, the MDAs transfer rates were highest in GP to PS in both ages than PS to broiler and within GP to PS at 50 weeks of age, it was highest (94.87%) than 30 weeks of age. Accordingly, the poultry producer may help to develop an effective vaccination schedule by considering the MDAs from above experiment.

  • 36.
    Al-Kass, Z.
    et al.
    Swedish Univ Agr Sci SLU, Clin Sci, SE-75007 Uppsala, Sweden.;Univ Mosul, Coll Vet Med, Dept Surg & Theriogenol, Mosul, Iraq..
    Guo, Y.
    Swedish Univ Agr Sci SLU, Clin Sci, SE-75007 Uppsala, Sweden..
    Vinnere, Olga
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Niazi, A.
    Swedish Univ Agr Sci, SLU Global Bioinformat Ctr, Dept Anim Breeding & Genet, SE-75007 Uppsala, Sweden..
    Morrell, J. M.
    Swedish Univ Agr Sci SLU, Clin Sci, SE-75007 Uppsala, Sweden..
    Metagenomic analysis of bacteria in stallion semen2020Ingår i: Animal Reproduction Science, ISSN 0378-4320, E-ISSN 1873-2232, Vol. 221, artikel-id 106568Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Bacteria colonize stallion semen during collection and processing which may cause disease in inseminated females or negatively affect sperm quality during storage prior to insemination. Antibiotics are added to semen extenders to control the growth of these bacteria but may induce antimicrobial resistance. Research into alternatives to antibiotics for this purpose requires knowledge of which bacteria are present in semen. Not all bacteria in semen, however, can be identified by conventional microbiological techniques. The objectives of the study were to: i) determine which bacteria are present in stallion semen using metagenomics; and ii) investigate individual differences in bacterial content in semen from all stallions on one premises. Bacterial DNA was extracted from ejaculates from seven stallions (one ejaculate per stallion) and bacteria were identified using 16S sequencing. In total, 83 bacterial genera were identified, varying from 25 to 52 among different individuals. There was a negative correlation (r = -0.81212; P < 0.05) between the presence of Treponema spp. and Advenella spp. In conclusion, most of the bacteria present in stallion semen could be identified to genus level by 16S sequencing even when present at a low frequency. This method of identification may help to clarify individual variation in bacterial content and its potential effects on fertility.

  • 37.
    Allkja, Jontana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    The influence of copper on mast cell during bacterial infections2017Självständigt arbete på avancerad nivå (masterexamen), 30 poäng / 45 hpStudentuppsats (Examensarbete)
    Abstract [en]

    Mast cells are innate immune cells generally known for their harmful effects, particularly their role in asthma and autoimmune diseases. However, they can also recognize pathogens and mount a response to them. Copper is essential for proper cell function and homeostasis. Research has shown that changes in copper levels can affect mast cell morphology and gene expression of many of its immune mediators. It has also been shown that the copper transporter Ctr2 plays an important role in mast cell physiology. In this project, we investigated whether the same effects can be seen when mast cells are stimulated with bacteria, namely Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). For this purpose, wild type and Ctr2 knockout mast cells were treated with different concentrations of copper for 72 hours and later co-cultured with either S. aureus or E. coli. Wild type cells were also treated with a copper chelator to investigate the effect of copper starvation. Release of IL-6 and CCL2, two common mediators released in response to bacteria, were measured by ELISA, while their gene expression was measured by qPCR. Results showed that either copper starvation or, 10 μM copper cause an increase in IL-6 and CCL2 protein levels, but have no effect on gene expression. The 10 μM copper effect was not observed in the Ctr2 knockout cells. In conclusion, not much is known about the mechanisms involved in the mast cell response to bacteria. However, it appears that copper can affect either different stages of the same pathway, or different pathways in a similar manner.

  • 38.
    Almeida, Rafael M.
    et al.
    Univ Fed Juiz de Fora, Inst Ciencias Biol, Dept Biol, Aquat Ecol Lab, Juiz De Fora, Brazil..
    Nobrega, Gabriel N.
    Univ Sao Paulo, Escola Super Agr Luiz de Queiroz, Dept Ciencia Solo, Piracicaba, Brazil..
    Junger, Pedro C.
    Univ Fed Rio de Janeiro, Lab Limnol, Rio De Janeiro, Brazil..
    Figueiredo, Aline V.
    Univ Fed Rio Grande do Norte, Lab Water Resources & Environm Sanitat, BR-59072970 Natal, RN, Brazil..
    Andrade, Anizio S.
    Univ Fed Rio Grande do Norte, Lab Limnol, BR-59072970 Natal, RN, Brazil..
    de Moura, Caroline G. B.
    Univ Fed Rio Grande do Norte, Lab Limnol, BR-59072970 Natal, RN, Brazil..
    Tonetta, Denise
    Univ Fed Santa Catarina, Lab Freshwater Ecol, Florianopolis, SC, Brazil..
    Oliveira, Ernandes S., Jr.
    Radboud Univ Nijmegen, Dept Aquat Ecol & Environm Biol, Inst Water & Wetland Res, NL-6525 ED Nijmegen, Netherlands..
    Araujo, Fabiana
    Univ Fed Rio Grande do Norte, Lab Water Resources & Environm Sanitat, BR-59072970 Natal, RN, Brazil..
    Rust, Felipe
    Univ Fed Juiz de Fora, Inst Ciencias Biol, Dept Biol, Aquat Ecol Lab, Juiz De Fora, Brazil..
    Pineiro-Guerra, Juan M.
    Univ Republica, Dept Ecol Teor & Aplicada, Ctr Univ Reg Este, Montevideo, Uruguay.;Univ Republica, Fac Ciencias, Montevideo, Uruguay..
    Mendonca, Jurandir R., Jr.
    Univ Fed Rio Grande do Norte, Lab Water Resources & Environm Sanitat, BR-59072970 Natal, RN, Brazil..
    Medeiros, Leonardo R.
    Univ Fed Rio Grande do Norte, Lab Limnol, BR-59072970 Natal, RN, Brazil..
    Pinheiro, Lorena
    Univ Fed Estado Rio de Janeiro, Dept Ciencias Nat, Rio De Janeiro, Brazil..
    Miranda, Marcela
    Univ Fed Juiz de Fora, Inst Ciencias Biol, Dept Biol, Aquat Ecol Lab, Juiz De Fora, Brazil..
    Costa, Mariana R. A.
    Univ Fed Rio Grande do Norte, Lab Water Resources & Environm Sanitat, BR-59072970 Natal, RN, Brazil..
    Melo, Michaela L.
    Univ Fed Sao Carlos, Lab Microbial Proc & Biodivers, BR-13560 Sao Carlos, SP, Brazil..
    Nobre, Regina L. G.
    Univ Fed Rio Grande do Norte, Lab Limnol, BR-59072970 Natal, RN, Brazil..
    Benevides, Thiago
    Univ Fed Rio de Janeiro, Lab Limnol, Rio De Janeiro, Brazil..
    Roland, Fabio
    Univ Fed Juiz de Fora, Inst Ciencias Biol, Dept Biol, Aquat Ecol Lab, Juiz De Fora, Brazil..
    de Klein, Jeroen
    Wageningen Univ, Aquat Ecol & Environm Sci, NL-6700 AP Wageningen, Netherlands..
    Barros, Nathan O.
    Univ Fed Juiz de Fora, Inst Ciencias Biol, Dept Biol, Aquat Ecol Lab, Juiz De Fora, Brazil..
    Mendonca, Raquel
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Limnologi. Univ Fed Juiz de Fora, Inst Ciencias Biol, Dept Biol, Aquat Ecol Lab, Juiz De Fora, Brazil.
    Becker, Vanessa
    Univ Fed Rio Grande do Norte, Lab Water Resources & Environm Sanitat, BR-59072970 Natal, RN, Brazil..
    Huszar, Veral. M.
    Univ Fed Rio de Janeiro, Museu Nacl, Lab Ficol, Rio De Janeiro, Brazil..
    Kosten, Sarian
    Radboud Univ Nijmegen, Dept Aquat Ecol & Environm Biol, Inst Water & Wetland Res, NL-6525 ED Nijmegen, Netherlands..
    High Primary Production Contrasts with Intense Carbon Emission in a Eutrophic Tropical Reservoir2016Ingår i: Frontiers in Microbiology, E-ISSN 1664-302X, Vol. 7, artikel-id 717Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Recent studies from temperate lakes indicate that eutrophic systems tend to emit less carbon dioxide (Co-2) and bury more organic carbon (OC) than oligotrophic ones, rendering them CO2 sinks in some cases. However, the scarcity of data from tropical systems is critical for a complete understanding of the interplay between eutrophication and aquatic carbon (C) fluxes in warm waters. We test the hypothesis that a warm eutrophic system is a source of both CO2 and CH4 to the atmosphere, and that atmospheric emissions are larger than the burial of OC in sediments. This hypothesis was based on the following assumptions: (i) OC mineralization rates are high in warm water systems, so that water column CO2 production overrides the high C uptake by primary producers, and (ii) increasing trophic status creates favorable conditions for CH4 production. We measured water-air and sediment-water CO2 fluxes, CH4 diffusion, ebullition and oxidation, net ecosystem production (NEP) and sediment OC burial during the dry season in a eutrophic reservoir in the semiarid northeastern Brazil. The reservoir was stratified during daytime and mixed during nighttime. In spite of the high rates of primary production (4858 +/- 934 mg C m(-2) d(-1)), net heterotrophy was prevalent due to high ecosystem respiration (5209 +/- 992 mg C m(-2) d(-1)). Consequently, the reservoir was a source of atmospheric CO2 (518 +/- 182 mg C m(-2) d(-1)). In addition, the reservoir was a source of ebullitive (17 +/- 10 mg C m(-2) d(-1)) and diffusive CH4 (11 +/- 6 mg C m(-2) d(-1)). OC sedimentation was high (1162 mg C m(-2) d(-1)), but our results suggest that the majority of it is mineralized to CO2 (722 +/- 182 mg C m(-2) d(-1)) rather than buried as OC (440 mg C m(-2) d(-1)). Although temporally resolved data would render our findings more conclusive, our results suggest that despite being a primary production and OC burial hotspot, the tropical eutrophic system studied here was a stronger CO2 and CH4 source than a C sink, mainly because of high rates of OC mineralization in the water column and sediments.

    Ladda ner fulltext (pdf)
    fulltext
  • 39.
    Alström, Per
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för evolutionsbiologi, Systematisk zoologi.
    Species Limits and Systematics in Some Passerine Birds2002Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    I use morphological, vocal, molecular, behavioural, ecological and distributional data to re-evaluate the systematics of three passerine bird groups, the Mirafraassamica complex (bush-larks), the genus Seicercus ("spectacled-warblers"; with emphasis on the the S. burkii complex) and the genus Motacilla (wagtails). Two new species are described: Seicercus soror and Motacilla samveasnae. I propose that the polytypic species M. assamica should be treated as four separate species: M. assamica, M. affinis, M. microptera and M. marionae (it is also remarked that the proper name of the latter is M. erythrocephala). That is primarily supported by vocalisations and mitochondrial DNA. The latter data set also suggests that M. assamica sensu lato is paraphyletic, since M. erythroptera, which is always treated as a separate species, is nested within the M. assamica complex. I propose that the polytypic species S. burkii comprises six sibling species. Some of these are found to breed sympatrically, although mainly or entirely segregated altitudinally. Mitochondrial DNA suggests that the S. burkii complex is non-monophyletic, and also that the divergence of the different taxa is much older than indicated by morphological and vocal data. According to the molecular phylogeny, both the genera Seicercus and its assumed sister genus Phylloscopus are paraphyletic. That is corroborated by independent data. The phylogenetic study of the genus Motacilla reveals incongruence between mitochondrial DNA, nuclear DNA and non-molecular data. I conclude that the nuclear gene tree reflects the organismal phylogeny more faithfully than the mitochondrial gene tree. The latter is likely to have been affected by introgressive hybridisation, possibly also stochastic lineage sorting. The most remarkable result that is strongly supported by both mitochondrial and nuclear DNA is that M. flava is non-monophyletic.

    Ladda ner fulltext (pdf)
    FULLTEXT01
  • 40.
    Altgård, Sofia
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för biologisk grundutbildning.
    Berggren, Sofia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för biologisk grundutbildning.
    Björklund, Viktor
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för biologisk grundutbildning.
    Lundsten, Sara
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för biologisk grundutbildning.
    Olafsson, Thorsteinn
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för biologisk grundutbildning.
    Pettersson, Lovisa
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för biologisk grundutbildning.
    Ett nytt multiplext PCR-protokoll för identifiering och detektion av Shigella och enteroinvasiv E. coli (EIEC) från livsmedel2014Självständigt arbete på grundnivå (kandidatexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
    Abstract [en]

    This report is the result of a project in the course Independent Projekt in Molecular Biotechnology at Uppsala University during the spring of 2014. The foremost purpose of the course is to give students the opportunity to carry through exstensive work in a project environment. This project was formed based on a comission from the biotechnology company SweTree Technologies, and the goal has been to compose a summary of the different techniques and methods that exist in the field of mass propagation of trees through the method of somatic embryogenesis.

    The project group has obtained information about the area mainly throgh reading patents, trying to find key components and bottlenecks in other companies’ somatic embryogenesis technologies. This paper is divided into different sections, containing the patents of the automation of different steps in the process. This is to make it easier for readers to find information about the area they are interested in, as well as to illustrate the main parts of the process as percieved by the project group.

    Currently, there are several automated solutions for almost every step in the process, some of which are already in use. All the information obtained shows that the cost and labour has decreased with the development of this technology. While there is still room for significant devolopment in order to produce a complete automated process, there is no doubt that this method is becoming an ever more important asset in the area of forestry. Our hope is that this report may be a useful tool for companies or laymen to geta grasp of the field of automated mass production of trees.

    Ladda ner fulltext (pdf)
    fulltext
  • 41. Alvarez, Beatriz
    et al.
    Krogh-Andersen, Kasper
    Tellgren-Roth, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Martinez, Noelia
    Guenaydin, Goekce
    Lin, Yin
    Cruz Martin, M.
    Alvarez, Miguel A.
    Hammarstroem, Lennart
    Marcotte, Harold
    An Exopolysaccharide-Deficient Mutant of Lactobacillus rhamnosus GG Efficiently Displays a Protective Llama Antibody Fragment against Rotavirus on Its Surface2015Ingår i: Applied and Environmental Microbiology, ISSN 0099-2240, E-ISSN 1098-5336, Vol. 81, nr 17, s. 5784-5793Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Rotavirus is the leading cause of infantile diarrhea in developing countries, where it causes a high number of deaths among infants. Two vaccines are available, being highly effective in developed countries although markedly less efficient in developing countries. As a complementary treatment to the vaccines, a Lactobacillus strain producing an anti-rotavirus antibody fragment in the gastrointestinal tract could potentially be used. In order to develop such an alternative therapy, the effectiveness of Lactobacillus rhamnosus GG to produce and display a VHH antibody fragment (referred to as anti-rotavirus protein 1 [ARP1]) on the surface was investigated. L. rhamnosus GG is one of the best-characterized probiotic bacteria and has intrinsic antirotavirus activity. Among four L. rhamnosus GG strains [GG (CMC), GG (ATCC 53103), GG (NCC 3003), and GG (UT)] originating from different sources, only GG (UT) was able to display ARP1 on the bacterial surface. The genomic analysis of strain GG (UT) showed that the genes welE and welF of the EPS cluster are inactivated, which causes a defect in exopolysaccharide (EPS) production, allowing efficient display of ARP1 on its surface. Finally, GG (UT) seemed to confer a level of protection against rotavirus-induced diarrhea similar to that of wild-type GG (NCC 3003) in a mouse pup model, indicating that the EPS may not be involved in the intrinsic antirotavirus activity. Most important, GG (EM233), a derivative of GG (UT) producing ARP1, was significantly more protective than the control strain L. casei BL23.

  • 42.
    Ament-Velasquez, S. Lorena
    et al.
    Stockholm Univ, Dept Zool, Div Populat Genet, Stockholm, Sweden..
    Vogan, Aaron A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Systematisk biologi.
    Podospora anserina2022Ingår i: Trends in Microbiology, ISSN 0966-842X, E-ISSN 1878-4380, Vol. 30, nr 12, s. 1243-1244Artikel i tidskrift (Övrigt vetenskapligt)
    Ladda ner fulltext (pdf)
    FULLTEXT01
  • 43.
    Amlinger, Lina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    The type I-E CRISPR-Cas system: Biology and applications of an adaptive immune system in bacteria2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    CRISPR-Cas systems are adaptive immune systems in bacteria and archaea, consisting of a clustered regularly interspaced short palindromic repeats (CRISPR) array and CRISPR associated (Cas) proteins. In this work, the type I-E CRISPR-Cas system of Escherichia coli was studied.

    CRISPR-Cas immunity is divided into three stages. In the first stage, adaptation, Cas1 and Cas2 store memory of invaders in the CRISPR array as short intervening sequences, called spacers. During the expression stage, the array is transcribed, and subsequently processed into small CRISPR RNAs (crRNA), each consisting of one spacer and one repeat. The crRNAs are bound by the Cascade multi-protein complex. During the interference step, Cascade searches for DNA molecules complementary to the crRNA spacer. When a match is found, the target DNA is degraded by the recruited Cas3 nuclease.

    Host factors required for integration of new spacers into the CRISPR array were first investigated. Deleting recD, involved in DNA repair, abolished memory formation by reducing the concentration of the Cas1-Cas2 expression plasmid, leading to decreased amounts of Cas1 to levels likely insufficient for spacer integration. Deletion of RecD has an indirect effect on adaptation. To facilitate detection of adaptation, a sensitive fluorescent reporter was developed where an out-of-frame yfp reporter gene is moved into frame when a new spacer is integrated, enabling fluorescent detection of adaptation. Integration can be detected in single cells by a variety of fluorescence-based methods. A second aspect of this thesis aimed at investigating spacer elements affecting target interference. Spacers with predicted secondary structures in the crRNA impaired the ability of the CRISPR-Cas system to prevent transformation of targeted plasmids. Lastly, in absence of Cas3, Cascade was successfully used to inhibit transcription of specific genes by preventing RNA polymerase access to the promoter.

    The CRISPR-Cas field has seen rapid development since the first demonstration of immunity almost ten years ago. However, much research remains to fully understand these interesting adaptive immune systems and the research presented here increases our understanding of the type I-E CRISPR-Cas system. 

    Delarbeten
    1. Deletion of recD indirectly reduce adaptation in the type I-E CRISPR-Cas system
    Öppna denna publikation i ny flik eller fönster >>Deletion of recD indirectly reduce adaptation in the type I-E CRISPR-Cas system
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Mikrobiologi
    Identifikatorer
    urn:nbn:se:uu:diva-312230 (URN)
    Tillgänglig från: 2017-01-08 Skapad: 2017-01-08 Senast uppdaterad: 2017-01-09
    2. Quantification of CRISPR-Cas spacer integration using a fluorescent reporter
    Öppna denna publikation i ny flik eller fönster >>Quantification of CRISPR-Cas spacer integration using a fluorescent reporter
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Mikrobiologi
    Identifikatorer
    urn:nbn:se:uu:diva-312231 (URN)
    Tillgänglig från: 2017-01-08 Skapad: 2017-01-08 Senast uppdaterad: 2017-01-09
    3. Effect of spacer sequence on efficiency of Type I-E CRISPR-Cas systems
    Öppna denna publikation i ny flik eller fönster >>Effect of spacer sequence on efficiency of Type I-E CRISPR-Cas systems
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Mikrobiologi
    Identifikatorer
    urn:nbn:se:uu:diva-312233 (URN)
    Tillgänglig från: 2017-01-08 Skapad: 2017-01-08 Senast uppdaterad: 2017-01-09
    4. Efficient programmable gene silencing by Cascade
    Öppna denna publikation i ny flik eller fönster >>Efficient programmable gene silencing by Cascade
    Visa övriga...
    2015 (Engelska)Ingår i: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 43, nr 1, s. 237-246Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Methods that permit controlled changes in the expression of genes are important tools for biological and medical research, and for biotechnological applications. Conventional methods are directed at individually changing each gene, its regulatory elements or its mRNA's translation rate. We demonstrate that the CRISPR-associated DNA-binding Cascade complex can be used for efficient, long-lasting and programmable gene silencing. When Cascade is targeted to a promoter sequence the transcription of the downstream gene is inhibited, resulting in dramatically reduced expression. The specificity of Cascade binding is provided by the integral crRNA component, which is easily designed to target virtually any stretch of DNA. Cascade targeted to the ORF sequence of the gene can also silence expression, albeit at lower efficiency. The system can be used to silence plasmid and chromosome targets, simultaneously target several genes and is active in different bacterial species and strains. The findings described here are an addition to the expanding range of CRISPR-based technologies and may be adapted to additional organisms and cell systems.

    Nationell ämneskategori
    Biokemi och molekylärbiologi
    Identifikatorer
    urn:nbn:se:uu:diva-249042 (URN)10.1093/nar/gku1257 (DOI)000350207100026 ()25435544 (PubMedID)
    Tillgänglig från: 2015-04-23 Skapad: 2015-04-10 Senast uppdaterad: 2018-02-28Bibliografiskt granskad
    Ladda ner fulltext (pdf)
    fulltext
    Ladda ner (jpg)
    preview image
  • 44.
    Amlinger, Lina
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Hoekzema, Mirthe
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Wagner, E. Gerhart H.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Koskiniemi, Sanna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Lundgren, Magnus
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Quantification of CRISPR-Cas spacer integration using a fluorescent reporterManuskript (preprint) (Övrigt vetenskapligt)
  • 45.
    Amlinger, Lina
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Larsson, Martin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Koskiniemi, Sanna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Lundgren, Magnus
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Deletion of recD indirectly reduce adaptation in the type I-E CRISPR-Cas systemManuskript (preprint) (Övrigt vetenskapligt)
  • 46.
    Amlinger, Lina
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Saunders, Sita J.
    Lundgren, Magnus
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Backofen, Rolf
    Effect of spacer sequence on efficiency of Type I-E CRISPR-Cas systemsManuskript (preprint) (Övrigt vetenskapligt)
  • 47.
    Anagandula, Mahesh
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Hyöty, Heikki
    University of Tampere, School of Medicine, Tampere, Finland ,Fimlab Ltd, Pirkanmaa Hospital District, Finland.
    Frisk, Gun
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Enterovirus-induced changes in explanted human islet of Langerhans resemble findings in islets of fulminant and conventional type 1 diabetesManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Hypothesis: Fulminant Type 1 diabetes is a unique subtype of T1D, mostly reported in the Japanese population, which is characterized by extensive beta cell death already at onset, often without any insulitis. Enterovirus (EV) infections are associated with the etiology of both fulminant and conventional T1D. However the causative mechanism is not known for any of these diseases. EVs capability to cause lytic vs non-lytic infection in explanted human islets may have implications on the pathogenesis of these two types of T1D.

    Aim: To study the effect of infection of explanted human pancreatic islets with lytic (CBV-1) and non-lytic (CBV-4) Coxsackie B virus strains on cytopathic effect/islet disintegration and to what extent genes involved in viral sensing, antiviral defense and encoding of islet auto-antigens are affected by the viral replication. Also, to compare these findings with the findings reported in fulminant and conventional T1D.

    Methods: Degree of cytopathic effect/islet disintegration was studied and viral replication was measured. Genes involved in viral sensing (NOD2, TLR7 and TLR4), antiviral pathways (OAS2, MX1, PKR, and IRF7), genes coding for known islet auto antigens (GAD65, ZNT8) and the islet hormones, insulin and glucagon, were studied. Mock-infected explanted islet served as controls.

    Results: All CBV strains replicated in the explanted islets but only the CBV-1 strains caused cytopathic effect/islet cell disintegration. Infection with all CBV strains resulted in the induction of genes encoding OAS2 and MX1. In contrast, mRNA expression levels of the gene encoding insulin was reduced. The gene encoding PKR was induced by one of the lytic strains (CBV-1-11) and also by the non-lytic CBV4 strain, while the mRNA expression levels of genes encoding glucagon, NOD2, TLR7, TLR4, MCL1, GAD65 and ZNT8 were not significantly affected.

  • 48.
    Anagandula, Mahesh
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Richardson, Sarah J.
    University of Exeter Medical School, Institute of Biomedical and Clinical Science, Exeter, UK.
    Oberste, M. Steven
    Centers for Disease Control and Prevention, Atlanta, Georgia.
    Sioofy-Khojine, Amir-Babak
    School of Medicine, University of Tampere, Tampere, Finland.
    Hyoty, Heikki
    School of Medicine, University of Tampere, Tampere, Finland ,Fimlab Ltd, Pirkanmaa Hospital District, Finland.
    Morgan, Noel G.
    University of Exeter Medical School, Institute of Biomedical and Clinical Science, Exeter, UK.
    Korsgren, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Frisk, Gun
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Infection of Human Islets of Langerhans With Two Strains of Coxsackie B Virus Serotype 1: Assessment of Virus Replication, Degree of Cell Death and Induction of Genes Involved in the Innate Immunity Pathway2014Ingår i: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 86, nr 8, s. 1402-1411Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Type 1 diabetes mellitus is believed to be triggered, in part, by one or more environmental factors and human enteroviruses (HEVs) are among the candidates. Therefore, this study has examined whether two strains of HEV may differentially affect the induction of genes involved in pathways leading to the synthesis of islet hormones, chemokines and cytokines in isolated, highly purified, human islets. Isolated, purified human pancreatic islets were infected with strains of Coxsackievirus B1. Viral replication and the degree of CPE/islet dissociation were monitored. The expression of insulin, glucagon, CXCL10, TLR3, IF1H1, CCL5, OAS-1, IFN beta, and DDX58 was analyzed. Both strains replicated in islets but only one of strain caused rapid islet dissociation/CPE. Expression of the insulin gene was reduced during infection of islets with either viral strain but the gene encoding glucagon was unaffected. All genes analyzed which are involved in viral sensing and the development of innate immunity were induced by Coxsackie B viruses, with the notable exception of TLR3. There was no qualitative difference in the expression pattern between each strain but the magnitude of the response varied between donors. The lack of virus induced expression of TLR3, together with the differential regulation of IF1H1, OAS1 and IFN beta, (each of which has polymorphic variants influence the predisposition to type 1 diabetes), that might result in defective clearance of virus from islet cells. The reduced expression of the insulin gene and the unaffected expression of the gene encoding glucagon by Coxsackie B1 infection is consistent with the preferential beta-cell tropism of the virus.

  • 49. Anders, Alfjorden
    et al.
    Astvaldsson, Asgeir
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Eva, Jansson
    Svärd, Staffan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Experimental challenge of Atlantic salmon (Salmo salar) with the diplomonad parasite Spironucleus salmonicida to characterize the infection cycleManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Experimental infections were performed of Atlantic salmon (Salmo salar) from the Baltic Sea region with the Diplomonad fish parasite Spironucleus salmonicida in order to define the infection cycle, specifically the time-line and putative routes of transmission. An oral infection protocol using axenic parasites was developed, as were new diagnostic tools using PCR and specific antibodies. We also produced firefly luciferase expressing S. salmonicida parasites that could be identified in the infected fish using in vivo and ex vivo imaging. The new tools made it possible to follow the S. salmonicida infection cycle in detail. Three different stages of the infection were identified: one initial intestinal stage, followed by a blood stage and a final tissue stage. Parasites intubated into the intestine attached to the intestinal surface and were identified in the blood after 1-3 weeks. Skin lesions and infections of the muscles, internal organs and eyes were seen 4-10 weeks after initiation of infection. Several morphologically different forms of S. salmonicida cells were detected in ex vivo cell-cultures of biopsies from skin lesions. By this infection trial we have been able to show that S. salmonicida may use several alternative routes of transmission. One alternative is the fecal-oral route, similar to other Diplomonad parasites but the parasites can also be excreted directly into the surrounding water from the mucous layer of the skin or from an ulcerated skin lesion. This information can be used to prevent the transmission of the parasite in fish farms.

  • 50.
    Andersson, Dan I.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Balaban, Nathalie Q.
    Hebrew Univ Jerusalem, Racah Inst Phys, Edmond J Safra Campus, IL-9190401 Jerusalem, Israel.
    Baquero, Fernando
    Ramon Y Cajal Hlth Res Inst, Dept Microbiol, Ctra Colmenar Viejo Km 9, Madrid 28034, Spain.
    Courvalin, Patrice
    Inst Pasteur, French Natl Reference Ctr Antibiot, 25-28 Rue Dr Roux, F-75015 Paris, France.
    Glaser, Philippe
    Inst Pasteur, Ecol & Evolut Antibiot Resistance, 25-28 Rue Dr Roux, F-75015 Paris, France.
    Gophna, Uri
    Tel Aviv Univ, Sch Mol Cell Biol & Biotechnol, 121 Jack Green Bldg, IL-6997801 Tel Aviv, Israel.
    Kishony, Roy
    Technion, Fac Biol, IL-3200003 Haifa, Israel.
    Molin, Søren
    Tech Univ Denmark, Novo Nordisk Fdn Ctr Biosustainabil, Kemitorvet Bldg 220, DK-2800 Lyngby, Denmark.
    Tønjum, Tone
    Univ Oslo, Dept Microbiol, OUS HF Rikshosp, Postboks 4950, N-0424 Oslo, Norway; Oslo Univ Hosp, POB 4950, N-0424 Oslo, Norway.
    Antibiotic resistance: turning evolutionary principles into clinical reality2020Ingår i: FEMS Microbiology Reviews, ISSN 0168-6445, E-ISSN 1574-6976, Vol. 44, nr 2, s. 171-188Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Antibiotic resistance is one of the major challenges facing modern medicine worldwide. The past few decades have witnessed rapid progress in our understanding of the multiple factors that affect the emergence and spread of antibiotic resistance at the population level and the level of the individual patient. However, the process of translating this progress into health policy and clinical practice has been slow. Here, we attempt to consolidate current knowledge about the evolution and ecology of antibiotic resistance into a roadmap for future research as well as clinical and environmental control of antibiotic resistance. At the population level, we examine emergence, transmission and dissemination of antibiotic resistance, and at the patient level, we examine adaptation involving bacterial physiology and host resilience. Finally, we describe new approaches and technologies for improving diagnosis and treatment and minimizing the spread of resistance.

1234567 1 - 50 av 1054
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf