| 1. |
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| 2. |
- Broman, T, et al.
(författare)
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Molecular Detection of Persistent Francisella tularensis Subspecies holarctica in Natural Waters
- 2011
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Ingår i: International Journal of Microbiology. - : Hindawi Publishing Corporation. - 1687-918X .- 1687-9198. ; 2011, s. Article ID 851946-
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Tidskriftsartikel (refereegranskat)abstract
- Tularemia, caused by the bacterium Francisella tularensis, where F. tularensis subspecies holarctica has long been the cause of endemic disease in parts of northern Sweden. Despite this, our understanding of the natural life-cycle of the organism is still limited. During three years, we collected surface water samples (n = 341) and sediment samples (n = 245) in two areas in Sweden with endemic tularemia. Real-time PCR screening demonstrated the presence of F. tularenis lpnA sequences in 108 (32%) and 48 (20%) of the samples, respectively. The 16S rRNA sequences from those samples all grouped to the species F. tularensis. Analysis of the FtM19InDel region of lpnA-positive samples from selected sampling points confirmed the presence of F. tularensis subspecies holarctica-specific sequences. These sequences were detected in water sampled during both outbreak and nonoutbreak years. Our results indicate that diverse F. tularensis-like organisms, including F. tularensis subsp. holarctica, persist in natural waters and sediments in the investigated areas with endemic tularemia.
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| 3. |
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| 4. |
- Lampe, E. O., et al.
(författare)
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A study of virulence factors in the fish pathogen F. noatunensis ssp noatunensis
- 2013
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Ingår i: Fish and Shellfish Immunology. - : Elsevier. - 1050-4648 .- 1095-9947. ; 34:6, s. 1716-1716
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Tidskriftsartikel (refereegranskat)abstract
- The bacterium Francisella noatunensis ssp. noatunensis (in text: F. noatunensis) is the ethiological agent of the disease francisellosis in Atlantic cod. Francisellosis has been one of the major limiting factors in the development of Norwegian aquaculture industry based on Atlantic cod. Lacking an effective treatment or vaccine there is urgent need for studies related to the pathogenesis of the disease.The closely related human pathogen F. tularensis is more extensively studied and due to relatively high sequence similarity with F. noatunensis, indirect evidence on important virulence factors can be obtained by reverse genetics. The Francisella Pathogenicity Island (FPI) has been identified in all sequenced genomes of Francisella sp. and contains genes associated with the ability of the bacterium to survive and replicate within macrophages.To elucidate the pathogenesis of F. noatunensis, infection assays have been performed on primary cells extracted from the head kidney of Atlantic cod. Disruptive mutations of the potential virulence factors IglC, IglD (important for intracellular growth in F. tularensis subsp.) and ClpB (a heat shock protein identified in F. tularensis), have been constructed in F. noatunensis and the infection pattern is in the process of characterization. Model systems that are utilized in the characterization are the amoebae and professional phagocyte Dictyostelium discoideum, zebrafish and macrophages extracted from head kidney of Atlantic cod.
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| 5. |
- Sjöstedt, E, et al.
(författare)
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The first nurse-patient encounter in a psychiatric setting : discovering a moral commitment in nursing.
- 2001
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Ingår i: Nursing Ethics. - : SAGE Publications. - 0969-7330 .- 1477-0989. ; 8:4, s. 313-27
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to deepen nurses' understanding of the importance of carefully managing the first nurse-patient encounter in a psychiatric setting according to each patient's suffering and future hopes. The study was carried out using an action research approach. The action planned was the implementation of a conceptual model reflecting Eriksson's caring theory. Data were collected by interviews with nurses and observational notes kept in a research diary. The data analysis followed the procedure of qualitative content analysis. A generalization of the entire learning process shows the first nurse-patient encounter to be a moral commitment in nursing. A theoretical framework of nursing assessment conveying knowledge about the patient as unique and being a whole person can support the nurse in encouraging the patient to enter into a relationship. This insight stimulated the nurses in this study to reflect on the moral responsibility of continuing the relationship and initiating an ongoing nursing process. Awareness of this responsibility made them reflect more on the possibility of nurses taking autonomous actions in order not to abandon the patient and to avoid feeling guilty.
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| 6. |
- Alam, Athar, et al.
(författare)
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The Role of ClpB in Bacterial Stress Responses and Virulence
- 2021
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Ingår i: Frontiers in Molecular Biosciences. - : Frontiers Media S.A.. - 2296-889X. ; 8
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Forskningsöversikt (refereegranskat)abstract
- Bacterial survival within a mammalian host is contingent upon sensing environmental perturbations and initiating an appropriate counter-response. To achieve this, sophisticated molecular machineries are used, where bacterial chaperone systems play key roles. The chaperones are a prerequisite for bacterial survival during normal physiological conditions as well as under stressful situations, e.g., infection or inflammation. Specific stress factors include, but are not limited to, high temperature, osmolarity, pH, reactive oxidative species, or bactericidal molecules. ClpB, a member of class 1 AAA+ proteins, is a key chaperone that via its disaggregase activity plays a crucial role for bacterial survival under various forms of stress, in particular heat shock. Recently, it has been reported that ClpB also regulates secretion of bacterial effector molecules related to type VI secretion systems. In this review, the roles of ClpB in stress responses and the mechanisms by which it promotes survival of pathogenic bacteria are discussed.
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| 7. |
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| 8. |
- Bruhn, Anders Dalhoff, et al.
(författare)
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Terrestrial Dissolved Organic Matter Mobilized From Eroding Permafrost Controls Microbial Community Composition and Growth in Arctic Coastal Zones
- 2021
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Ingår i: Frontiers in Earth Science. - : Frontiers Media SA. - 2296-6463. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Climate warming is accelerating erosion along permafrost-dominated Arctic coasts. This results in the additional supply of organic matter (OM) and nutrients into the coastal zone. In this study we investigate the impact of coastal erosion on the marine microbial community composition and growth rates in the coastal Beaufort Sea. Dissolved organic matter (DOM) derived from three representative glacial deposit types (fluvial, lacustrine, and moraine) along the Yukon coastal plain, Canada, were used as substrate to cultivate marine bacteria using a chemostat setup. Our results show that DOM composition (inferred from UV-Visible spectroscopy) and biodegradability (inferred from DOC concentration, bacterial production and respiration) significantly differ between the three glacial deposit types. DOM derived from fluvial and moraine types show clear terrestrial characteristics with low aromaticity (Sr: 0.63 ± 0.02 and SUVA254: 1.65 ± 0.06 L mg C−1 m−1 & Sr: 0.68 ± 0.01 and SUVA254: 1.17 ± 0.06 L mg C−1 m−1, respectively) compared to the lacustrine soil type (Sr: 0.71 ± 0.02 and SUVA254: 2.15 ± 0.05 L mg C−1 m−1). The difference in composition of DOM leads to the development of three different microbial communities. Whereas Alphaproteobacteria dominate in fluvial and lacustrine deposit types (67 and 87% relative abundance, respectively), Gammaproteobacteria is the most abundant class for moraine deposit type (88% relative abundance). Bacterial growth efficiency (BGE) is 66% for DOM from moraine deposit type, while 13 and 28% for DOM from fluvial and lacustrine deposit types, respectively. The three microbial communities therefore differ strongly in their net effect on DOM utilization depending on the eroded landscape type. The high BGE value for moraine-derived DOM is probably caused by a larger proportion of labile colorless DOM. These results indicate that the substrate controls marine microbial community composition and activities in coastal waters. This suggests that biogeochemical changes in the Arctic coastal zone will depend on the DOM character of adjacent deposit types, which determine the speed and extent of DOM mineralization and thereby carbon channeling into the microbial food web. We conclude that marine microbes strongly respond to the input of terrestrial DOM released by coastal erosion and that the landscape type differently influence marine microbes.
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| 9. |
- Bröms, Jeanette E, 1974-, et al.
(författare)
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A conserved α-helix essential for a type VI secretion-like system of Francisella tularensis
- 2009
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Ingår i: Journal of Bacteriology. - 0021-9193 .- 1098-5530. ; 191:8, s. 2431-2446
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Tidskriftsartikel (refereegranskat)abstract
- Francisella tularensis harbors genes with similarity to genes encoding components of a type VI secretion system (T6SS) recently identified in several gram-negative bacteria. These include iglA and iglB, the homologues of which are conserved in most T6SSs. We used a yeast two-hybrid system to study the interaction of the Igl proteins of F. tularensis LVS. We identified a region of IglA, encompassing residues 33-132, necessary for efficient binding to IglB as well as for IglAB protein stability and intra-macrophage growth. In particular, residues 103-122, overlapping with a highly conserved alpha-helix, played an absolutely essential role. Point mutations within this domain caused modest defects in IglA-IglB binding in yeast, but markedly impaired intra-macrophage replication and phagosomal escape, resulting in severe attenuation of LVS in mice. Thus, IglA-IglB complex formation is clearly crucial for Francisella pathogenicity. This interaction may be universal to T6S, since IglAB homologues of Yersinia pseudotuberculosis, Pseudomonas aeruginosa, Vibrio cholerae, Salmonella typhimurium and Escherichia coli were also shown to interact in yeast and the interaction was dependent on the preservation of the same alpha-helix. Heterologous interactions formed between non-native IglAB proteins further supported the notion of a conserved binding site. Thus, IglA-IglB complex formation is clearly crucial for Francisella pathogenicity and the same interaction is conserved in other human pathogens.
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| 10. |
- Bröms, Jeanette E., et al.
(författare)
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A functional VipA-VipB interaction is required for the type VI secretion system activity of Vibrio cholerae O1 strain A1552
- 2013
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Ingår i: BMC Microbiology. - London, England : BioMed Central. - 1471-2180. ; 13, s. 96-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Many Gram-negative bacteria rely on a type VI secretion system (T6SS) to infect eukaryotic cells or to compete against other microbes. Common to these systems is the presence of two conserved proteins, in Vibrio cholerae denoted VipA and VipB, which have been shown to interact in many clinically relevant pathogens. In this study, mutagenesis of a defined region within the VipA protein was used to identify residues important for VipB binding in V. cholerae O1 strain A1552. Results: A dramatically diminished interaction was shown to correlate with a decrease in VipB stability and a loss of hemolysin co-regulated protein (Hcp) secretion and rendered the bacterium unable to compete with Escherichia coli in a competition assay. Conclusions: This confirms the biological relevance of the VipA-VipB interaction, which is essential for the T6SS activity of many important human pathogens.
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| 11. |
- Bröms, Jeanette E., et al.
(författare)
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A mutagenesis-based approach identifies amino acids in the N-terminal part of Francisella tularensis IglE that critically control type VI system-mediated secretion
- 2017
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Ingår i: Virulence. - : TAYLOR & FRANCIS INC. - 2150-5594 .- 2150-5608. ; 8:6, s. 821-847
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Tidskriftsartikel (refereegranskat)abstract
- The Gram-negative bacterium Francisella tularensis is the etiological agent of the zoonotic disease tularemia. Its life cycle is characterized by an ability to survive within phagocytic cells through phagosomal escape and replication in the cytosol, ultimately causing inflammasome activation and host cell death. Required for these processes is the Francisella Pathogenicity Island (FPI), which encodes a Type VI secretion system (T6SS) that is active during intracellular infection. In this study, we analyzed the role of the FPI-component IglE, a lipoprotein which we previously have shown to be secreted in a T6SS-dependent manner. We demonstrate that in F. tularensis LVS, IglE is an outer membrane protein. Upon infection of J774 cells, an Delta iglE mutant failed to escape from phagosomes, and subsequently, to multiply and cause cytopathogenicity. Moreover, Delta iglE was unable to activate the inflammasome, to inhibit LPS-stimulated secretion of TNF-alpha, and showed marked attenuation in the mouse model. In F. novicida, IglE was required for in vitro secretion of IglC and VgrG. A mutagenesis-based approach involving frameshift mutations and alanine substitution mutations within the first similar to 38 residues of IglE revealed that drastic changes in the sequence of the extreme N-terminus (residues 2-6) were well tolerated and, intriguingly, caused hyper-secretion of IglE during intracellular infection, while even subtle mutations further downstream lead to impaired protein function. Taken together, this study highlights the importance of IglE in F. tularensis pathogenicity, and the contribution of the N-terminus for all of the above mentioned processes.
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| 12. |
- Bröms, Jeanette E, et al.
(författare)
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Dissection of the Functions of the IglC Protein of Francisella tularensis
- 2010
-
Ingår i: The challenge of highly pathogenic microorganisms. - Dordrecht : Springer. - 9789048190539 - 9789048190546 ; , s. 67-75
-
Konferensbidrag (refereegranskat)abstract
- Francisella tularensis harbors genes with similarity to genes encoding components of a type VI secretion system (T6SS). These include iglA and iglB, the homologues of which are conserved in T6SSs. They are part of the igl operon, also encompassing the iglC and iglD genes. We have used a yeast two-hybrid system to study the interaction of the Igl proteins of E tularensis LVS. Previously, we identified a region of IglA necessary for efficient binding to IglB as well as for IglAB protein stability and intra-macrophage growth with an essential role for a conserved alpha-helical region. Thus, IglA-IglB complex formation is clearly crucial for Francisella pathogenicity and the same interaction is conserved in other human pathogens. Herein, the interaction of IglC with other members of the operon was investigated. It showed no binding to the other members in the yeast two-hybrid assay and we found also that two cysteine residues, C191 and C192, predicted to be putative prenylation sites, played no role for the important contribution of IglC to the intracellular replication of E tularensis although C191 was important for the stability of the protein.
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| 13. |
- Bröms, Jeanette E., et al.
(författare)
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DotU and VgrG, core components of type VI secretion systems, are essential for Francisella LVS pathogenicity
- 2012
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:4
-
Tidskriftsartikel (refereegranskat)abstract
- The Gram-negative bacterium Francisella tularensis causes tularemia, a disease which requires bacterial escape from phagosomes of infected macrophages. Once in the cytosol, the bacterium rapidly multiplies, inhibits activation of the inflammasome and ultimately causes death of the host cell. Of importance for these processes is a 33-kb gene cluster, the Francisella pathogenicity island (FPI), which is believed to encode a type VI secretion system (T6SS). In this study, we analyzed the role of the FPI-encoded proteins VgrG and DotU, which are conserved components of type VI secretion (T6S) clusters. We demonstrate that in F. tularensis LVS, VgrG was shown to form multimers, consistent with its suggested role as a trimeric membrane puncturing device in T6SSs, while the inner membrane protein DotU was shown to stabilize PdpB/IcmF, another T6SS core component. Upon infection of J774 cells, both Delta vgrG and Delta dotU mutants did not escape from phagosomes, and subsequently, did not multiply or cause cytopathogenicity. They also showed impaired activation of the inflammasome and marked attenuation in the mouse model. Moreover, all of the DotU-dependent functions investigated here required the presence of three residues that are essentially conserved among all DotU homologues. Thus, in agreement with a core function in T6S clusters, VgrG and DotU play key roles for modulation of the intracellular host response as well as for the virulence of F. tularensis.
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| 14. |
- Bröms, Jeanette E, 1974-, et al.
(författare)
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IglG and IglI of the Francisella pathogenicity island are important virulence determinants of Francisella tularensis LVS
- 2011
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Ingår i: Infection and Immunity. - : American Society for Microbiology. - 0019-9567 .- 1098-5522. ; 79:9, s. 3683-3696
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Tidskriftsartikel (refereegranskat)abstract
- The Gram-negative bacterium Francisella tularensis is the causative agent of tularemia, a disease intimately associated with the multiplication of the bacterium within host macrophages. This in turn requires the expression of Francisella pathogenicity island (FPI) genes, believed to encode a type VI secretion system. While the exact functions of many of the components have yet to be revealed, some have been found to contribute to the ability of Francisella to cause systemic infection in mice as well as to prevent phagolysosomal fusion and facilitate escape into the host cytosol. Upon reaching this compartment, the bacterium rapidly multiplies, inhibits activation of the inflammasome, and ultimately causes apoptosis of the host cell. In this study, we analyzed the contribution of the FPI-encoded proteins IglG, IglI, and PdpE to the aforementioned processes in F. tularensis LVS. The ΔpdpE mutant behaved similarly to the parental strain in all investigated assays. In contrast, ΔiglG and ΔiglI mutants, although they were efficiently replicating in J774A.1 cells, both exhibited delayed phagosomal escape, conferred a delayed activation of the inflammasome, and exhibited reduced cytopathogenicity as well as marked attenuation in the mouse model. Thus, IglG and IglI play key roles for modulation of the intracellular host response and also for the virulence of F. tularensis.
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| 15. |
- Bröms, Jeanette E, 1974-, et al.
(författare)
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The role of the Francisella Tularensis pathogenicity island in type VI secretion, intracellular survival, and modulation of host cell signaling
- 2010
-
Ingår i: Frontiers in microbiology. - : Frontiers Media SA. - 1664-302X. ; 1, s. 136-
-
Tidskriftsartikel (refereegranskat)abstract
- Francisella tularensis is a highly virulent gram-negative intracellular bacterium that causes the zoonotic disease tularemia. Essential for its virulence is the ability to multiply within host cells, in particular monocytic cells. The bacterium has developed intricate means to subvert host immune mechanisms and thereby facilitate its intracellular survival by preventing phagolysosomal fusion followed by escape into the cytosol, where it multiplies. Moreover, it targets and manipulates numerous host cell signaling pathways, thereby ameliorating the otherwise bactericidal capacity. Many of the underlying molecular mechanisms still remain unknown but key elements, directly or indirectly responsible for many of the aforementioned mechanisms, rely on the expression of proteins encoded by the Francisella pathogenicity island (FPI), suggested to constitute a type VI secretion system. We here describe the current knowledge regarding the components of the FPI and the roles that have been ascribed to them.
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| 16. |
- Bröms, Jeanette E., et al.
(författare)
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Unique substrates secreted by the type VI secretion system of Francisella tularensis during intramacrophage infection
- 2012
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:11
-
Tidskriftsartikel (refereegranskat)abstract
- Gram-negative bacteria have evolved sophisticated secretion machineries specialized for the secretion of macromolecules important for their life cycles. The Type VI secretion system (T6SS) is the most widely spread bacterial secretion machinery and is encoded by large, variable gene clusters, often found to be essential for virulence. The latter is true for the atypical T6SS encoded by the Francisella pathogenicity island (FPI) of the highly pathogenic, intracellular bacterium Francisella tularensis. We here undertook a comprehensive analysis of the intramacrophage secretion of the 17 FPI proteins of the live vaccine strain, LVS, of F. tularensis. All were expressed as fusions to the TEM beta-lactamase and cleavage of the fluorescent substrate CCF2-AM, a direct consequence of the delivery of the proteins into the macrophage cytosol, was followed over time. The FPI proteins IglE, IglC, VgrG, IglI, PdpE, PdpA, IglJ and IglF were all secreted, which was dependent on the core components DotU, VgrG, and IglC, as well as IglG. In contrast, the method was not directly applicable on F. novicida U112, since it showed very intense native beta-lactamase secretion due to FTN_1072. Its role was proven by ectopic expression in trans in LVS. We did not observe secretion of any of the LVS substrates VgrG, IglJ, IglF or IglI, when tested in a FTN_1072 deficient strain of F. novicida, whereas IglE, IglC, PdpA and even more so PdpE were all secreted. This suggests that there may be fundamental differences in the T6S mechanism among the Francisella subspecies. The findings further corroborate the unusual nature of the T6SS of F. tularensis since almost all of the identified substrates are unique to the species.
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| 17. |
- Champion, Mia D, et al.
(författare)
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Comparative genomic characterization of Francisella tularensis strains belonging to low and high virulence subspecies
- 2009
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Ingår i: PLoS pathogens. - : Public Library of Science (PLoS). - 1553-7374. ; 5:5, s. e1000459-
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Tidskriftsartikel (refereegranskat)abstract
- Tularemia is a geographically widespread, severely debilitating, and occasionally lethal disease in humans. It is caused by infection by a gram-negative bacterium, Francisella tularensis. In order to better understand its potency as an etiological agent as well as its potential as a biological weapon, we have completed draft assemblies and report the first complete genomic characterization of five strains belonging to the following different Francisella subspecies (subsp.): the F. tularensis subsp. tularensis FSC033, F. tularensis subsp. holarctica FSC257 and FSC022, and F. tularensis subsp. novicida GA99-3548 and GA99-3549 strains. Here, we report the sequencing of these strains and comparative genomic analysis with recently available public Francisella sequences, including the rare F. tularensis subsp. mediasiatica FSC147 strain isolate from the Central Asian Region. We report evidence for the occurrence of large-scale rearrangement events in strains of the holarctica subspecies, supporting previous proposals that further phylogenetic subdivisions of the Type B clade are likely. We also find a significant enrichment of disrupted or absent ORFs proximal to predicted breakpoints in the FSC022 strain, including a genetic component of the Type I restriction-modification defense system. Many of the pseudogenes identified are also disrupted in the closely related rarely human pathogenic F. tularensis subsp. mediasiatica FSC147 strain, including modulator of drug activity B (mdaB) (FTT0961), which encodes a known NADPH quinone reductase involved in oxidative stress resistance. We have also identified genes exhibiting sequence similarity to effectors of the Type III (T3SS) and components of the Type IV secretion systems (T4SS). One of the genes, msrA2 (FTT1797c), is disrupted in F. tularensis subsp. mediasiatica and has recently been shown to mediate bacterial pathogen survival in host organisms. Our findings suggest that in addition to the duplication of the Francisella Pathogenicity Island, and acquisition of individual loci, adaptation by gene loss in the more recently emerged tularensis, holarctica, and mediasiatica subspecies occurred and was distinct from evolutionary events that differentiated these subspecies, and the novicida subspecies, from a common ancestor. Our findings are applicable to future studies focused on variations in Francisella subspecies pathogenesis, and of broader interest to studies of genomic pathoadaptation in bacteria.
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| 18. |
- Churie Kallhauge, Angela, et al.
(författare)
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Global challenges : Furthering the multilateral process for sustainable development
- 2017
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- The World Summit on Sustainable Development (WSSD) in Johannesburg 2002 was the latest conference in an international process to manage environment and development issues that can be traced back to the late 1960s. Three milestones mark this 30-year process of social and political interaction: the United Nations Conference on the Human Environment (UNCHE), held in Stockholm in 1972, the first international meeting at a high political level convened to address environmental issues; the 1992 United Nations Conference on Environment and Development (UNCED), held in Rio de Janeiro; and the WSSD, which attempted to set policy goals and targets for the global environmental and developmental challenges previously identified.But what did the WSSD achieve? Following the summit there have been various opinions of its significance and its outputs, many of them negative. This book argues that there is a need to place the WSSD in its broader context. Understanding the connections between the WSSD and its precedents as well as those between this overall process and individual environmental decision-making processes (such as on climate change), and how they all contribute to the overall global policy process, adds a critical dimension to the analysis of the WSSD outcomes. This book examines the challenges facing the global policy process for sustainable development as it continues beyond Johannesburg into the future. It combines a forward outlook with a historical perspective in tracing the evolution of selected cross-cutting themes on the agenda of the three conferences, the institutions and formal results of the process, and the actors and their patterns of interaction over time. The focus is on the decision-making dimension - the multilateral negotiations-which can be seen as the development over time of a pattern of interlinked political activities.Global Challenges has four operational objectives: first, to define the ongoing process that formally began with the Stockholm Conference in 1972 and evolved towards its latest major manifestation at the WSSD; second, to present some dynamics of the Stockholm-Rio-Johannesburg (SRJ) process by exploring the themes identified; third, to introduce an approach on how to consider the outcomes of this process as a way of reflecting on what the process has actually accomplished; and, finally, to discuss lessons learned for theory and practice from this exercise. The practical lessons include reflections on how the continued SRJ process should best be organised and supported into the future. The book takes a uniquely broad outlook and interdisciplinary approach in addressing important lessons relating to the emergence of substantive issues as well as to process and institutional dynamics. It is a bridge-building exercise from academic analysis to long-term strategic thinking in environmental regime building. Global Challenges provides a new perspective on the continuing and increasingly complex global environment and development policy process and analyses the interlinkages between the process, trends and cross-cutting issues that set the conditions for the global efforts to achieve sustainable development. It will be essential reading for academics and practitioners interested in seeing the big picture of the global challenges facing people and planet in the 21st century.
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| 19. |
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| 20. |
- Evengård, Birgitta, 1952-, et al.
(författare)
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Healthy ecosystems for human and animal health : Science diplomacy for responsible development in the Arctic
- 2021
-
Ingår i: Polar Record. - : Cambridges Institutes Press. - 0032-2474 .- 1475-3057. ; 57
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Tidskriftsartikel (refereegranskat)abstract
- Climate warming is occurring most rapidly in the Arctic, which is both a sentinel and a driver of further global change. Ecosystems and human societies are already affected by warming. Permafrost thaws and species are on the move, bringing pathogens and vectors to virgin areas. During a five-year project, the CLINF - a Nordic Center of Excellence, funded by the Nordic Council of Ministers, has worked with the One Health concept, integrating environmental data with human and animal disease data in predictive models and creating maps of dynamic processes affecting the spread of infectious diseases. It is shown that tularemia outbreaks can be predicted even at a regional level with a manageable level of uncertainty. To decrease uncertainty, rapid development of new and harmonised technologies and databases is needed from currently highly heterogeneous data sources. A major source of uncertainty for the future of contaminants and infectious diseases in the Arctic, however, is associated with which paths the majority of the globe chooses to follow in the future. Diplomacy is one of the most powerful tools Arctic nations have to influence these choices of other nations, supported by Arctic science and One Health approaches that recognise the interconnection between people, animals, plants and their shared environment at the local, regional, national and global levels as essential for achieving a sustainable development for both the Arctic and the globe.
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| 21. |
- Fagerberg, Linn, et al.
(författare)
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Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics
- 2014
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 13:2, s. 397-406
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Tidskriftsartikel (refereegranskat)abstract
- Global classification of the human proteins with regards to spatial expression patterns across organs and tissues is important for studies of human biology and disease. Here, we used a quantitative transcriptomics analysis (RNA-Seq) to classify the tissue-specific expression of genes across a representative set of all major human organs and tissues and combined this analysis with antibody- based profiling of the same tissues. To present the data, we launch a new version of the Human Protein Atlas that integrates RNA and protein expression data corresponding to 80% of the human protein-coding genes with access to the primary data for both the RNA and the protein analysis on an individual gene level. We present a classification of all human protein-coding genes with regards to tissue-specificity and spatial expression pattern. The integrative human expression map can be used as a starting point to explore the molecular constituents of the human body.
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| 22. |
- Gustavsson, Fredrik, et al.
(författare)
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Magnetic moment and anisotropy at the Fe/ZnSe(001) interface studied by conversion electron Mössbauer spectroscopy
- 2002
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 66:2, s. 024405-
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Tidskriftsartikel (refereegranskat)abstract
- The interface magnetic properties of Fe/ZnSe heterostructures grown on GaAs(001) by molecular-beam epitaxy have been investigated using conversion electron Mössbauer spectroscopy (CEMS) and macroscopic magnetic measurements. For Fe films thinner than 100 Å an in-plane 〈110〉 uniaxial magnetic anisotropy was found and the magnetization loops could successfully be described by the simple Stoner-Wohlfarth model, which implies that the magnetization reverses only by coherent rotation and jump processes. For the interface analysis, a 5-Å-thick layer of enriched 57Fe was deposited on the ZnSe surface and buried under 20 Å of natural Fe. In this way the 57Fe serves as a local probe of the interface magnetic environment in a bulklike Fe film since the CEMS technique is only sensitive to this isotope of Fe. An interface magnetic moment of 2.18 μB was found and, in relation to 2.2 μB for bulk bcc Fe, this precludes the presence of any interface reactions. Surprisingly, however, the direction of the interface magnetic moment turned out to be reoriented from the [110] direction by almost 30°, an effect that was assumed to arise from the distribution of unidirectional tetrahedral bonds present on the Zn c(2×2) reconstructed ZnSe surface.
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| 23. |
- Holmberg, Ellinor, et al.
(författare)
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Allopregnanolone involvement in feeding regulation, overeating and obesity
- 2018
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Ingår i: Frontiers in neuroendocrinology (Print). - : Academic Press. - 0091-3022 .- 1095-6808. ; 48, s. 70-77
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Forskningsöversikt (refereegranskat)abstract
- Obesity is strongly associated with ill health, primarily caused by consumption of excessive calories, and promoted (inter alia) by gamma-amino-butyric-acid (GABA) stimulating food intake by activating GABA(A) receptors (primarily with alpha 3 and alpha 2 subunits) in the hypothalamic arcuate nucleus and paraventricular nucleus. Allopregnanolone is a potent positive GABAA receptor modulating steroid (GAMS). As reviewed here, elevated allopregnanolone levels are associated with increases in food intake, preferences for energy-rich food, and obesity in humans and other mammals. In women with polycystic ovarian disease, high serum allopregnanolone concentrations are linked to uncontrolled eating, and perturbed sensitivity to allopregnanolone. Increases in weight during pregnancy also correlate with increases in allopregnanolone levels. Moreover, Prader-Willis syndrome is associated with massive overeating, absence of a GABA(A) receptor (with compensatory > 12-, > 5- and > 1.5-fold increases in alpha 4, gamma 2, and alpha 1, alpha 3 subunits), and increases in the alpha 4, beta x, delta receptor subtype, which is highly sensitive to allopregnanolone. GABA and positive GABA-A receptor modulating steroids like allopregnanolone stimulates food intake and weight gain.
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| 24. |
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| 25. |
- Kumar, Rajender, et al.
(författare)
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Exploring the Diversity Within the Genus Francisella – An Integrated Pan-Genome and Genome-Mining Approach
- 2020
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Ingår i: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Pan-genome analysis is a powerful method to explore genomic heterogeneity and diversity of bacterial species. Here we present a pan-genome analysis of the genus Francisella, comprising a dataset of 63 genomes and encompassing clinical as well as environmental isolates from distinct geographic locations. To determine the evolutionary relationship within the genus, we performed phylogenetic whole-genome studies utilizing the average nucleotide identity, average amino acid identity, core genes and non-recombinant loci markers. Based on the analyses, the phylogenetic trees obtained identified two distinct clades, A and B and a diverse cluster designated C. The sizes of the pan-, core-, cloud-, and shell-genomes of Francisella were estimated and compared to those of two other facultative intracellular pathogens, Legionella and Piscirickettsia. Francisella had the smallest core-genome, 692 genes, compared to 886 and 1,732 genes for Legionella and Piscirickettsia respectively, while the pan-genome of Legionella was more than twice the size of that of the other two genera. Also, the composition of the Francisella Type VI secretion system (T6SS) was analyzed. Distinct differences in the gene content of the T6SS were identified. In silico approaches performed to identify putative substrates of these systems revealed potential effectors targeting the cell wall, inner membrane, cellular nucleic acids as well as proteins, thus constituting attractive targets for site-directed mutagenesis. The comparative analysis performed here provides a comprehensive basis for the assessment of the phylogenomic relationship of members of the genus Francisella and for the identification of putative T6SS virulence traits.
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| 26. |
- Lindgren, Marie, et al.
(författare)
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The Francisella tularensis LVS ΔpdpC mutant exhibits a unique phenotype during intracellular infection
- 2013
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Ingår i: BMC Microbiology. - : BioMed Central. - 1471-2180. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: A prerequisite for the virulence of the facultative intracellular bacterium Francisella tularensis is effective intramacrophage proliferation, which is preceded by phagosomal escape into the cytosol, and ultimately leads to host cell death. Many components essential for the intracellular life cycle are encoded by a gene cluster, the Francisella pathogenicity island (FPI), constituting a type VI secretion system.Results: We characterized the FPI mutant ΔpdpC of the live vaccine strain (LVS) of F. tularensis and found that it exhibited lack of intracellular replication, incomplete phagosomal escape, and marked attenuation in the mouse model, however, unlike a phagosomally contained FPI mutant, it triggered secretion of IL-1β, albeit lower than LVS, and markedly induced LDH release.Conclusions: The phenotype of the ΔpdpC mutant appears to be unique compared to previously described F. tularensis FPI mutants.
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| 27. |
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| 28. |
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| 29. |
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| 30. |
- Lundin, S.E., et al.
(författare)
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Solvärme och säsongslagring med borrhål i berg och llågtemperatur för bostadsområdet Anneberg, Danderyd : Förprojektering
- 1998
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- In the planning of a new housing area for 100 dwellings, a pre-design has been made for a solar heating plant. The aim of designing a layout, is to compare the solar system with more conventional heating systems. Developers and contractors are invited for turn-key tenders of the different systems. The single family houses, apartments and service premises in two storey, will have a total floor area of 9000 m{sup 2}. The heating demand is estimated to 1100 MWh/year (120 kWh/m{sup 2}) and the power to 450 kW. A new concept system is designed with low temperatures in all essential parts, but heat pumps are not needed. (1) Flat plate solar collectors, mean temperature 60 deg C; (2) Seasonal bore hole heat store in rock, temperature level 30-45 deg C; (3) Heat distribution network, working temperature 20-80 deg C; (4) Floor heating coils, temperature 25-32 deg C; (5) Peak electrical heaters in houses; (6) Solar DHW and auxiliary individual electrical final heaters. The system has only one general heat fluid with a mixture of water and glycol flowing through solar collectors, store, culverts and the floor heating coils. In all operation modes the heat carrier has the same flow direction and even act as a`buffer volume`. The bedrock consist of outcrops of granite and the GWL is at a depth of 4 m below the ground. In a 120 m investigation bore hole, a so called`Response test` is made in situ of the rock and the duct system. The obtained thermal results are: Conductivity{lambda}= 4.1 W/m,K, Capacity C 0.6 kWh/K, m{sup 3}, Resistance total of PEM-tubes and rock mass R= 0.02 K/(W/m). The investment cost have been calculated to 5.4 mil SEK ({approx} 0.7 mil USD) excl. culvert, floor heating system, DHW tanks/heaters. The annual capital and running costs are 0.73 mil SEK (0.1 mil USD), calculated with an interest rate of 6% over 25 years (0.078). The total system heating cost will be 0.68 SEK/kWh (0.1 USD/kWh). With received EU- and -governmental subsides up to 2.0 mil SEK the heating costs drop to 0.54 SEK/kWh (0.07 USD/kWh). Solar energy is by that means cost-effective to conventional alternatives as district heating, bio-fuel block centrals, ground heat pumps or 100% electrical heating. The solar heating project seems in all respects possible to carry through - but the final decision is taken of the market response
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| 31. |
- Meyer, Lena, et al.
(författare)
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Microinjection of Francisella tularensis and Listeria monocytogenes reveals the importance of bacterial and host factors for successful replication
- 2015
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Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 83:8, s. 3233-3242
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Certain intracellular bacteria use the host cell cytosol as the replicative niche. Although it has been hypothesized that the successful exploitation of this compartment requires a unique metabolic adaptation, supportive evidence is lacking. For Francisella tularensis, many genes of the Francisella pathogenicity island (FPI) are essential for intracellular growth, and therefore, FPI mutants are useful tools for understanding the prerequisites of intracytosolic replication. We compared the growth of bacteria taken up by phagocytic or nonphagocytic cells with that of bacteria microinjected directly into the host cytosol, using the live vaccine strain (LVS) of F. tularensis; five selected FPI mutants thereof, i.e., Delta iglA, Delta iglC, Delta iglG, Delta iglI, and Delta pdpE strains; and Listeria monocytogenes. After uptake in bone marrow-derived macrophages (BMDM), ASC(-/-) BMDM, MyD88(-/-) BMDM, J774 cells, or HeLa cells, LVS, Delta pdpE and Delta iglG mutants, and L. monocytogenes replicated efficiently in all five cell types, whereas the Delta iglA and Delta iglC mutants showed no replication. After microinjection, all 7 strains showed effective replication in J774 macrophages, ASC(-/-) BMDM, and HeLa cells. In contrast to the rapid replication in other cell types, L. monocytogenes showed no replication in MyD88(-/-) BMDM and LVS showed no replication in either BMDM or MyD88(-/-) BMDM after microinjection. Our data suggest that the mechanisms of bacterial uptake as well as the permissiveness of the cytosolic compartment per se are important factors for the intracytosolic replication. Notably, none of the investigated FPI proteins was found to be essential for intracytosolic replication after microinjection.
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| 32. |
- Napier, Brooke A, et al.
(författare)
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Link between intraphagosomal biotin and rapid phagosomal escape in Francisella
- 2012
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 109:44, s. 18084-18089
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Tidskriftsartikel (refereegranskat)abstract
- Cytosolic bacterial pathogens require extensive metabolic adaptations within the host to replicate intracellularly and cause disease. In phagocytic cells such as macrophages, these pathogens must respond rapidly to nutrient limitation within the harsh environment of the phagosome. Many cytosolic pathogens escape the phagosome quickly (15-60 min) and thereby subvert this host defense, reaching the cytosol where they can replicate. Although a great deal of research has focused on strategies used by bacteria to resist antimicrobial phagosomal defenses and transiently pass through this compartment, the metabolic requirements of bacteria in the phagosome are largely uncharacterized. We previously identified a Francisella protein, FTN_0818, as being essential for intracellular replication and involved in virulence in vivo. We now show that FTN_0818 is involved in biotin biosynthesis and required for rapid escape from the Francisella-containing phagosome (FCP). Addition of biotin complemented the phagosomal escape defect of the FTN_0818 mutant, demonstrating that biotin is critical for promoting rapid escape during the short time that the bacteria are in the phagosome. Biotin also rescued the attenuation of the FTN_0818 mutant during infection in vitro and in vivo, highlighting the importance of this process. The key role of biotin in phagosomal escape implies biotin may be a limiting factor during infection. We demonstrate that a bacterial metabolite is required for phagosomal escape of an intracellular pathogen, providing insight into the link between bacterial metabolism and virulence, likely serving as a paradigm for other cytosolic pathogens.
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| 33. |
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| 34. |
- Ozanic, Mateja, et al.
(författare)
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The type IV pili component PilO is a virulence determinant of Francisella novicida
- 2022
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 17:1 1
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Tidskriftsartikel (refereegranskat)abstract
- Francisella tularensis is a highly pathogenic intracellular bacterium that causes the disease tularemia. While its ability to replicate within cells has been studied in much detail, the bacterium also encodes a less characterised type 4 pili (T4P) system. T4Ps are dynamic adhesive organelles identified as major virulence determinants in many human pathogens. In F. tularensis, the T4P is required for adherence to the host cell, as well as for protein secretion. Several components, including pilins, a pili peptidase, a secretin pore and two ATPases, are required to assemble a functional T4P, and these are encoded within distinct clusters on the Francisella chromosome. While some of these components have been functionally characterised, the role of PilO, if any, still is unknown. Here, we examined the role of PilO in the pathogenesis of F. novicida. Our results show that the PilO is essential for pilus assembly on the bacterial surface. In addition, PilO is important for adherence of F. novicida to human monocyte-derived macrophages, secretion of effector proteins and intracellular replication. Importantly, the pilO mutant is attenuated for virulence in BALB/c mice regardless of the route of infection. Following intratracheal and intradermal infection, the mutant caused no histopathology changes, and demonstrated impaired phagosomal escape and replication within lung liver as well as spleen. Thus, PilO is an essential virulence determinant of F. novicida.
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| 35. |
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| 36. |
- Rigard, Melanie, et al.
(författare)
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Francisella tularensis IglG Belongs to a Novel Family of PAAR-Like T6SS Proteins and Harbors a Unique N-terminal Extension Required for Virulence
- 2016
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 12:9
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Tidskriftsartikel (refereegranskat)abstract
- The virulence of Francisella tularensis, the etiological agent of tularemia, relies on an atypical type VI secretion system ( T6SS) encoded by a genomic island termed the Francisella Pathogenicity Island ( FPI). While the importance of the FPI in F. tularensis virulence is clearly established, the precise role of most of the FPI-encoded proteins remains to be deciphered. In this study, using highly virulent F. tularensis strains and the closely related species F. novicida, IglG was characterized as a protein featuring a unique alpha-helical N-terminal extension and a domain of unknown function ( DUF4280), present in more than 250 bacterial species. Three dimensional modeling of IglG and of the DUF4280 consensus protein sequence indicates that these proteins adopt a PAAR-like fold, suggesting they could cap the T6SS in a similar way as the recently described PAAR proteins. The newly identified PAAR-like motif is characterized by four conserved cysteine residues, also present in IglG, which may bind a metal atom. We demonstrate that IglG binds metal ions and that each individual cysteine is required for T6SS-dependent secretion of IglG and of the Hcp homologue, IglC and for the F. novicida intracellular life cycle. In contrast, the Francisella-specific N-terminal alpha-helical extension is not required for IglG secretion, but is critical for F. novicida virulence and for the interaction of IglG with another FPI-encoded protein, IglF. Altogether, our data suggest that IglG is a PAAR-like protein acting as a bi-modal protein that may connect the tip of the Francisella T6SS with a putative T6SS effector, IglF.
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| 37. |
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| 38. |
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| 39. |
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| 40. |
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| 41. |
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| 42. |
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| 43. |
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| 44. |
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| 45. |
- West, Christina E, et al.
(författare)
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Probiotic effects on T-cell maturation in infants during weaning.
- 2012
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Ingår i: Clinical and Experimental Allergy. - : John Wiley & Sons. - 0954-7894 .- 1365-2222. ; 42:4, s. 540-549
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Tidskriftsartikel (refereegranskat)abstract
- Background: We previously reported that feeding the probiotic Lactobacillus paracasei ssp. paracasei F19 (LF19) during weaning reduced the cumulative incidence of eczema.Objective: To investigate the impact of feeding LF19 on T-cell maturation.Methods: One hundred and seventy-nine healthy, term infants with no prior allergic manifestations were randomized to daily intake of cereals with (n = 89) or without (n = 90) the addition of LF19 108 colony forming units per serving from 4 to 13 months of age. Venous blood was drawn at 5.5 and 13 months of age. We used the cytokine response to polyclonal T-cell stimulation by anti-CD3 plus anti-CD28 monoclonal antibodies, and in vitro stimulation with the vaccine tetanus toxoid (TT) as measures of global adaptive immunity and capacity to raise a specific T-cell response, respectively. Expression levels of IL-2, IFN-γ, IL-4, IL-17A and IL-10 messenger RNAs (mRNAs) were used as proxies for general T-cell stimulation and naive Th0 cells, Th1-, Th2-, Th17- and T regulatory lineages.Results: There was no difference between the two groups at 5.5 months of age. At 13 months, the polyclonal IL-2 response was higher in the placebo group (P < 0.05), whereas the IFN-γ/IL-2 (P < 0.01) and IL-17A/IL-2 (P < 0.05) ratios after polyclonal stimulation were higher in the probiotic group, as was the TT-specific IL17-A response (P < 0.001). In both groups, the IFN-γ and IL-4 responses increased from 5.5 to 13 months upon both polyclonal and specific stimulation (P < 0.01), whereas the IL-10 response remained low (P > 0.05).Conclusion and Clinical Relevance: Our findings suggest modest effects by probiotics on T-cell maturation following 9 months of probiotic intake. Future studies should address if specific probiotics may drive immune development with possible preventive effects on the development of allergic disease.
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