| 1. |
- Arun, K. G., et al.
(författare)
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New horizons for fundamental physics with LISA
- 2022
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Ingår i: Living Reviews in Relativity. - : Springer Science and Business Media LLC. - 1433-8351 .- 2367-3613. ; 25:1
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Forskningsöversikt (refereegranskat)abstract
- The Laser Interferometer Space Antenna (LISA) has the potential to reveal wonders about the fundamental theory of nature at play in the extreme gravity regime, where the gravitational interaction is both strong and dynamical. In this white paper, the Fundamental Physics Working Group of the LISA Consortium summarizes the current topics in fundamental physics where LISA observations of gravitational waves can be expected to provide key input. We provide the briefest of reviews to then delineate avenues for future research directions and to discuss connections between this working group, other working groups and the consortium work package teams. These connections must be developed for LISA to live up to its science potential in these areas.
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| 2. |
- Bernhard, Sara, et al.
(författare)
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The outer membrane protein OlpA contributes to Moraxella catarrhalis serum resistance via interaction with factor H and the alternative pathway.
- 2014
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 210:8, s. 1306-1310
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Tidskriftsartikel (refereegranskat)abstract
- Factor H is an important complement regulator of the alternative pathway commonly recruited by pathogens for increased survival in the human host. The respiratory pathogen Moraxella catarrhalis that resides in the mucosa is highly serum resistant and causes otitis media in children and respiratory tract infections in individuals with underlying diseases. In this study, we show that M. catarrhalis binds factor H via the outer membrane protein OlpA. M. catarrhalis serum resistance was dramatically decreased in the absence of either OlpA or factor H, demonstrating that this inhibition of the alternative pathway significantly contributes to the virulence of M. catarrhalis.
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| 3. |
- Ekorong, Alain Fleury, et al.
(författare)
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Introduction : Assumer l’écart incommensurable entre poétique et politique du témoignage
- 2023
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Ingår i: Poétiques et politiques du témoignage dans la fiction contemporaine. - : Peter Lang Publishing Group. - 9782875744814 - 9782875744838 ; , s. 13-26
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Bokkapitel (refereegranskat)abstract
- J’ai passé ma première nuit de voyage à reconstruire dans ma mémoire le côté de chez Swann et c’était un excellent exercice d’abstraction. Moi aussi, je me suis longtemps couché de bonne heure, il faut dire. J’ai imaginé ce bruit ferrugineux de la sonnette, dans le jardin, les soirs où Swann venait dîner. J’ai revu dans la mémoire les couleurs du vitrail, dans l’église du village. Et cette haie d’aubépines, seigneur, cette haie d’aubépines était aussi mon enfance. J’ai passé la première nuit de ce voyage à reconstruire dans ma mémoire le côté de chez Swann et à me rappeler mon enfance (Semprun, 1963 : 42).Et voilà l’essentiel du message testimonial qui passe dans le sang de la réalité à travers l’épiderme de la fiction (Derrida, 1998)Dans le premier extrait, Jorge Semprun, survivant de l’Holocauste, réécrit cette première phrase de Proust pour évoquer le destin du souvenir. Le livre porte ainsi sur un narrateur se souvenant, l’effet de mise en abyme permettant d’installer le lecteur à la place du témoin de ce récit autobiographique. En effet, il s’agit bien ici de témoigner de l’indicible à partir de l’insertion de références littéraires accompagnant ce récit. Comme le rappelait Jorge Semprun dans un entretien, « quand j’ai écrit Le Grand Voyage, je l’ai fait avec l’innocence des déportés qui ont vécu le camp nazi » (Alliès, 1994 : 28). On sent bien ici la manière dont le témoignage individuel est relié à une mémoire collective, celle ←13 | 14→des déportés qui sont revenus et dont le défi immense était de rapporter les horreurs innommables qu’ils avaient vécues (Halbwachs, 1994). Le choix de la fiction est moins dû à une volonté d’esthétiser cette narration historique, qu’à un souci d’efficacité dans le montage de cette écriture. Dans cet ouvrage, Jorge Semprun utilise le futur du passé de manière systématique, car comme il l’écrivait, la génération de la Shoah avait pour mission d’être l’avenir d’une mémoire (Premat, 2018 : 194). Il s’agissait d’effectuer un choix entre l’écriture comme possibilité de relayer des témoignages individuels et collectifs et la vie comme disposition à l’oubli.
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| 4. |
- Fleury, Christophe, et al.
(författare)
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Identification of a Haemophilus influenzae Factor H-Binding Lipoprotein Involved in Serum Resistance.
- 2014
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 192:12, s. 5913-5923
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Tidskriftsartikel (refereegranskat)abstract
- Haemophilus influenzae is a Gram-negative human pathogen that resides in the upper respiratory tract. Encapsulated H. influenzae type b (Hib) and type f (Hif) are the most common serotypes associated with invasive disease. H. influenzae displays various strategies to circumvent the host innate immune response, including the bactericidal effect of the complement system. In this study, we identified an H. influenzae lipoprotein having the ability to bind factor H (FH), the major regulator of the alternative pathway of complement activation. This protein, named protein H (PH), was surface exposed and was found in all clinical Hib and Hif isolates tested. Deletion of the gene encoding for PH (lph) in Hib and Hif significantly reduced the interaction between bacteria and FH. When Hib and Hif PH variants were separately expressed in nontypeable (unencapsulated) H. influenzae, which did not bind FH, an increased FH affinity was observed. We recombinantly expressed the two PH variants in Escherichia coli, and despite sharing only 56% identical amino acids, both FH-binding Haemophilus proteins similarly interacted with the complement regulator FH short consensus repeats 7 and 18-20. Importantly, Hib and Hif resistance against the bactericidal effect of human serum was significantly reduced when bacterial mutants devoid of PH were tested. In conclusion, we have characterized a hitherto unknown bacterial protein that is crucial for mediating an interaction between the human pathogen H. influenzae and FH. This novel interaction is important for H. influenzae resistance against complement activation and will consequently promote bacterial pathogenesis.
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| 5. |
- Fleury, Christophe, et al.
(författare)
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Prevalence, distribution and transfer of small β-lactamase-containing plasmids in Swedish Haemophilus influenzae.
- 2014
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 1460-2091 .- 0305-7453. ; 69:5, s. 1238-1242
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Tidskriftsartikel (refereegranskat)abstract
- The β-lactamase genes of Haemophilus influenzae are commonly positioned on large integrative and conjugative elements, but a group of blaTEM-carrying small plasmids (4000-6000 bp) with a common structural backbone have recently been characterized. In this study we investigated the epidemiological significance and potential for transfer of this group of small plasmids.
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| 6. |
- Mogilenko, Denis A., et al.
(författare)
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Metabolic and Innate Immune Cues Merge into a Specific Inflammatory Response via the UPR
- 2019
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Ingår i: Cell. - : CELL PRESS. - 0092-8674 .- 1097-4172. ; 177:5, s. 1201-
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Tidskriftsartikel (refereegranskat)abstract
- Innate immune responses are intricately linked with intracellular metabolism of myeloid cells. Toll-like receptor (TLR) stimulation shifts intracellular metabolism toward glycolysis, while anti-inflammatory signals depend on enhanced mitochondrial respiration. How exogenous metabolic signals affect the immune response is unknown. We demonstrate that TLR-dependent responses of dendritic cells (DCs) are exacerbated by a high-fatty-acid (FA) metabolic environment. FAs suppress the TLR-induced hexokinase activity and perturb tricarboxylic acid cycle metabolism. These metabolic changes enhance mitochondria! reactive oxygen species (mtROS) production and, in turn, the unfolded protein response (UPR), leading to a distinct transcriptomic signature with IL-23 as hallmark. Interestingly, chemical or genetic suppression of glycolysis was sufficient to induce this specific immune response. Conversely, reducing mtROS production or DC-specific deficiency in XBP1 attenuated IL-23 expression and skin inflammation in an IL-23-dependent model of psoriasis. Thus, fine-tuning of innate immunity depends on optimization of metabolic demands and minimization of mtROS-induced UPR.
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| 7. |
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Poétiques et politiques du témoignage dans la fiction contemporaine
- 2023
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Samlingsverk (redaktörskap) (refereegranskat)abstract
- Le présent ouvrage a pour ambition de contribuer à une meilleure articulation des liens entre fiction et témoignage. Il présuppose que l’oeuvre littéraire, lorsqu’elle est lue autrement, constitue un lieu efficace de restitution de la vérité. En effet, les contributions de l’ouvrage partent toutes de la volonté d’une lecture de l’inéligible, une lecture de l’inexprimable, de l’indémontrable vérité, celle qui ne peut être affirmée qu’entre parenthèses, comme sous-titre, recul, pour repenser la manière dont la littérature témoigne. L’ouvrage réaffirme surtout l’idée que le témoignage déborde le cadre historique et juridique pour se constituer en tâtonnement vers l’inconnu, vers l’imprévu, vers des territoires non explorés, en quête de ce qui est vrai, et qui va au-delà de ce que nous appréhendons comme vérité. Le présent ouvrage montre que ce que la fiction fait au témoignage, c’est lui éviter de se faire doubler par une introduction – l’histoire introduit – et de réussir à parler éternellement pour ceux et celles qui ne peuvent le faire. L’ouvrage théorise avec force que la fiction littéraire libère le témoignage de l’opposition entre vérité et duplicité, car elle seule est à même de rendre obsolète la question de savoir si oui ou non le témoin dit la vérité. Nous affirmons que, peut-être, seule la fiction dit toute la vérité, permet de nous sacrifier nous-mêmes pour la vérité, jusqu’aux limites mêmes de l’innocence.
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| 8. |
- Singh, Birendra, et al.
(författare)
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Human pathogens utilize host extracellular matrix proteins laminin and collagen for adhesion and invasion of the host.
- 2012
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Ingår i: FEMS Microbiology Reviews. - : Oxford University Press (OUP). - 1574-6976. ; 36:6, s. 1122-1180
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Tidskriftsartikel (refereegranskat)abstract
- Laminin (Ln) and collagen are multifunctional glycoproteins that play an important role in cellular morphogenesis, cell signaling, tissue repair and cell migration. These proteins are ubiquitously present in tissues as a part of the basement membrane (BM), constitute a protective layer around blood capillaries, and are included in the extracellular matrix (ECM). As a component of BMs, both Lns and collagen(s) are found in the blood-brain barrier, and thus function as major mechanical containment molecules that protect tissues from pathogens. Invasive pathogens breach the basal lamina and degrade ECM proteins of interstitial spaces and connective tissues by using various ECM degrading proteases or surface-bound plasminogen and matrix metalloproteinases recruited from the host. Most pathogens associated with the respiratory, gastrointestinal, or urogenital tracts, as well as the CNS or the skin have the capacity to bind and degrade Lns and collagen(s) in order to adhere to and invade host tissues. In this review we focus on the adaptability of various pathogens to utilize these ECM proteins as enhancers for adhesion to host tissues or as a targets for degradation in order to breach the cellular barriers. The major pathogens discussed are Streptococcus, Staphylococcus, Pseudomonas, Salmonella, Yersinia, Treponema, Mycobacterium, Clostridium, Listeria, Porphyromonas and Haemophilus; Candida, Aspergillus, Pneumocystis, Cryptococcus and Coccidioides; Acanthamoeba, Trypanosoma and Trichomonas; Retrovirus and papilloma virus © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.
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| 9. |
- Su, Yu Ching, et al.
(författare)
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Haemophilus Protein F Orthologs of Pathogens Infecting the Airways : Exploiting Host Laminin at Heparin-Binding Sites for Maximal Adherence to Epithelial Cells
- 2017
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 216:10, s. 1303-1307
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Tidskriftsartikel (refereegranskat)abstract
- Haemophilus influenzae protein F (PF) is an important virulence factor interacting with laminin, an extracellular matrix protein ubiquitously expressed in the respiratory tract. Here we defined PF orthologs in Pseudomonas aeruginosa, Moraxella catarrhalis, and Staphylococcus aureus, bacteria that occasionally colonize and infect the human airways. Despite low sequence homology (48.2%-77.3% similarity), all orthologs (Paf, AfeA, and MntC) interacted with laminin. Interestingly, all proteins bound at the heparin-binding sites of laminin, including the globular domains, and also attached to laminin expressed on respiratory epithelial cells. Laminin is thus a highly important target for PF orthologs of the bacterial species examined.
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| 10. |
- Tamim, Al-Jubair, et al.
(författare)
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Haemophilus influenzae stores and distributes hemin by using Protein E.
- 2014
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Ingår i: International Journal of Medical Microbiology. - : Elsevier BV. - 1618-0607 .- 1438-4221. ; 304:5-6, s. 662-668
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Tidskriftsartikel (refereegranskat)abstract
- The human pathogen Haemophilus influenzae causes mainly respiratory tract infections such as acute otitis media in children and exacerbations in patients with chronic obstructive pulmonary disease. We recently revealed the crystal structure of H. influenzeae protein E (PE), a multifunctional adhesin that is involved in direct interactions with lung epithelial cells and host proteins. Based upon the PE structure we here suggest a hypothetical binding pocket that is compatible in size with a hemin molecule. An H. influenzae mutant devoid of PE bound significantly less hemin in comparison to the PE-expressing wild type counterpart. In addition, E. coli expressing PE at the surface resulted in a hemin-binding phenotype. An interaction between hemin and recombinant soluble PE was also demonstrated by native-PAGE and UV-visible spectrophotometry. Surface plasmon resonance revealed an affinity (Kd) of 1.6×10(-6)M for the hemin-PE interaction. Importantly, hemin that was bound to PE at the H. influenzae surface, was donated to co-cultured luciferase-expressing H. influenzae that were starved of hemin. When hemin is bound to PE it thus may serve as a storage pool for H. influenzae. To our knowledge this is the first report showing that H. influenzae can share hemin via a surface-located outer membrane protein.
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| 11. |
- Tamim, Al-Jubair, et al.
(författare)
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Haemophilus influenzae Type f Hijacks Vitronectin Using Protein H To Resist Host Innate Immunity and Adhere to Pulmonary Epithelial Cells.
- 2015
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 195:12, s. 5688-5695
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of invasive Haemophilus influenzae type b (Hib) disease has significantly decreased since the introduction of an efficient vaccine against Hib. However, in contrast to Hib, infections caused by H. influenzae serotype f (Hif) are emerging. We recently did a whole genome sequencing of an invasive Hif isolate, and reported that Hif interacts with factor H by expressing protein H (PH). In this study, upon screening with various human complement regulators, we revealed that PH is also a receptor for vitronectin (Vn), an abundant plasma protein that regulates the terminal pathway of the human complement system in addition to being a component of the extracellular matrix. Bacterial Vn binding was significantly reduced when the lph gene encoding PH was deleted in an invasive Hif isolate. The dissociation constant (KD) of the interaction between recombinant PH and Vn was 2.2 μM, as revealed by Biolayer interferometry. We found that PH has different regions for simultaneous interaction with both Vn and factor H, and that it recognized the C-terminal part of Vn (aa 352-362). Importantly, PH-dependent Vn binding resulted in better survival of the wild-type Hif or PH-expressing Escherichia coli when exposed to human serum. Finally, we observed that PH mediated an increased bacterial adherence to alveolar epithelial cells in the presence of Vn. In conclusion, our study reveals that PH most likely plays an important role in Hif pathogenesis by increasing serum resistance and adhesion to the airways.
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| 12. |
- Ünal, Can, et al.
(författare)
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QseC controls biofilm formation of non typeable Haemophilus influenzae in addition to an A1-2 dependent mechanism
- 2012
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Ingår i: International Journal of Medical Microbiology. - : Elsevier. - 1438-4221 .- 1618-0607. ; 302:6, s. 261-269
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Tidskriftsartikel (refereegranskat)abstract
- Non-typeable Haemophilus influenzae (NTHi) is a common pathogen associated with diseases such as acute otitis media or exacerbations in patients with chronic obstructive pulmonary disease. The biofilm-forming capability substantially contributes to the persistence of NTHi. However, the regulation of biofilm formation is not completely understood. Quorum sensing regulated by autoinducer-2 produced by luxS is until now the only described regulatory mechanism. In this study, we show that the two-component signalling system QseB/C is involved in the biofilm formation of NTHi in vitro. An isogenic NTHi mutant of qseC (Hi3655KR2) showed a significant decrease in biofilm formation under static and semi-static conditions as assessed by crystal violet staining. In addition, under constant flow conditions, Hi3655KR2 formed less biofilm after 48 h. The biofilm defects were irrespective of autoinducer-2 levels. Hence, here we suggest for the first time a regulatory circuit in NTHi, which controls biofilm formation by mechanisms other than or in addition to luxS-dependent factors.
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