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- Ferwerda, Bart, et al.
(författare)
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Functional and genetic evidence that the Mal/TIRAP allele variant 180L has been selected by providing protection against septic shock.
- 2009
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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. ; 106:25, s. 10272-10277
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Tidskriftsartikel (refereegranskat)abstract
- Adequate responses by our innate immune system toward invading pathogens were of vital importance for surviving infections, especially before the antibiotic era. Recently, a polymorphism in Mal (Ser180Leu, TIRAP rs8177374), an important adaptor protein downstream of the Toll-like receptor (TLR) 2 and 4 pathways, has been described to provide protection against a broad range of infectious pathogens. We assessed the functional effects of this polymorphism in human experimental endotoxemia, and we demonstrate that individuals bearing the TIRAP 180L allele display an increased, innate immune response to TLR4 and TLR2 ligands, but not to TLR9 stimulation. This phenotype has been related to an increased resistance to infection. However, an overshoot in the release of proinflammatory cytokines by TIRAP 180L homozygous individuals suggests a scenario of balanced evolution. We have also investigated the worldwide distribution of the Ser180Leu polymorphism in 14 populations around the globe to correlate the genetic makeup of TIRAP with the local infectious pressures. Based on the immunological, clinical, and genetic data, we propose that this mutation might have been selected in West Eurasia during the early settlement of this region after the out-of-Africa migration of modern Homo sapiens. This combination of functional and genetic data provides unique insights to our understanding of the pathogenesis of sepsis.
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| 4. |
- Tom, Brian A., et al.
(författare)
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Dissociative recombination of highly enriched para-H-3(+)
- 2009
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 130:3, s. 31101-
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Tidskriftsartikel (refereegranskat)abstract
- The determination of the dissociative recombination rate coefficient of H-3(+) has had a turbulent history, but both experiment and theory have recently converged to a common value. Despite this convergence, it has not been clear if there should be a difference between the rate coefficients for ortho-H-3(+) and para-H-3(+). A difference has been predicted theoretically and could conceivably impact the ortho:para ratio of H-3(+) in the diffuse interstellar medium, where H-3(+) has been widely observed. We present the results of an experiment at the CRYRING ion storage ring in which we investigated the dissociative recombination of highly enriched (similar to 83.6%) para-H-3(+) using a supersonic expansion source that produced ions with T-rot similar to 60-100 K. We observed an increase in the low energy recombination rate coefficient of the enriched para-H-3(+) by a factor of similar to 1.25 in comparison to H-3(+) produced from normal H-2 (ortho:para=3:1). The ratio of the rate coefficients of pure para-H-3(+) to that of pure ortho-H-3(+) is inferred to be similar to 2 at low collision energies; the corresponding ratio of the thermal rate coefficients is similar to 1.5 at electron temperatures from 60 to 1000 K. We conclude that this difference is unlikely to have an impact on the interstellar ortho:para ratio of H-3(+).
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| 5. |
- Larsson, Mats, et al.
(författare)
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The dissociative recombination of H-3(+) - a saga coming to an end?
- 2008
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Ingår i: Chemical Physics Letters. - : Elsevier BV. - 0009-2614 .- 1873-4448. ; 462:06-apr, s. 145-151
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Tidskriftsartikel (refereegranskat)abstract
- Major progress has been made in the understanding of how H-3(+) recombines with thermal and sub-thermal electrons, a process of great importance to the chemistry of diffuse interstellar clouds. Two independent ion storage ring experiments with rovibrationally cold H-3(+) ions are in excellent agreement, and quantum mechanical calculations agree with the storage ring results quantitatively for the thermal rate constant, if not in all details concerning the cross section. The recombination mechanism is understood. A direct consequence of this progress is that the cosmic-ray ionization rate in diffuse clouds must be shifted upwards to a value larger than 10 (16)s (1).
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