| 1. |
- Carrillo, M., et al.
(författare)
-
High-resolution crystal structures of transient intermediates in the phytochrome photocycle
- 2021
-
Ingår i: Structure. - : Elsevier BV. - 0969-2126. ; 29:7
-
Tidskriftsartikel (refereegranskat)abstract
- Phytochromes are red/far-red light photoreceptors in bacteria to plants, which elicit a variety of important physiological responses. They display a reversible photocycle between the resting Pr state and the light-activated Pfr state. Light signals are transduced as structural change through the entire protein to modulate its activity. It is unknown how the Pr-to-Pfr interconversion occurs, as the structure of intermediates remains notoriously elusive. Here, we present short-lived crystal structures of the photosensory core modules of the bacteriophytochrome from myxobacterium Stigmatella aurantiaca captured by an X-ray free electron laser 5 ns and 33 ms after light illumination of the Pr state. We observe large structural displacements of the covalently bound bilin chromophore, which trigger a bifurcated signaling pathway that extends through the entire protein. The snapshots show with atomic precision how the signal progresses from the chromophore, explaining how plants, bacteria, and fungi sense red light.
|
|
| 2. |
|
|
| 3. |
- Sorelius, Karl, et al.
(författare)
-
The Microbiology of Infective Native Aortic Aneurysms in a Population-Based Setting
- 2022
-
Ingår i: Annals of Vascular Surgery. - : Elsevier. - 0890-5096 .- 1615-5947. ; 78, s. 112-122
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim was to describe the microbiology of surgically treated infective native (mycotic) aortic aneurysms (INAAs), and associated survival and development of infection-related complications (IRCs). Methods: Data were pooled from 2 nationwide studies on surgically treated patients with INAAs in Sweden, between 1994 - 2016. Patients were grouped and analyzed according to culture results: 1) Staphylococcus aureus, 2) Streptococcus species (sp.), 3) Salmonella sp., 4) Enterococcus sp., 5) Gram-negative intestinal bacteria, 6) Other sp. (all other species found in culture), and 7) Negative cultures. Results: A sum of 182 patients were included, mean age 71 years (standard deviation; SD: 8.9). The median follow-up was 50.3 months (range 0 - 360). 128 (70.3%) patients had positive blood and/or tissue culture; Staphylococcus aureus n = 38 (20.9%), Streptococcus sp. n = 37 (20.3%), Salmonella sp. n = 19 (10.4%), Enterococcus sp. n = 16 (8.8%), Gram-negative intestinal bacteria n = 6, (3.3%), Other sp. n = 12 (6.6%) and Negative cultures n = 54 (29.7%). The estimated survival for the largest groups at 2-years after surgery was: Staphylococcus aureus 62% (95% Confidence interval 53.9 - 70.1), Streptococcus sp. 74.7% (67.4 - 82.0), Salmonella sp. 73.7% (63.6 - 83.8), Enterococcus sp. 61.9% (49.6 - 74.2), and Negative cultures 89.8% (85.5 - 94.1), P =.051. There were 37 IRCs (20.3%), and 19 (51.4%) were fatal, the frequency was insignificant between the groups. The majority of IRCs, 30/37 (81%), developed during the first postoperative year. Conclusion: In this assessment of microbiological findings of INAAs in Sweden, 50% of the pathogens were Staphylococcus aureus, Streptococcus sp., or Salmonella sp.. The overall 20%-frequency of IRCs, and its association with high mortality, motivates long-term antibiotic treatment regardless of microbial findings.
|
|
| 4. |
- Al-Rukn, S, et al.
(författare)
-
Stroke in the Middle-East and North Africa: A 2-year prospective observational study of intravenous thrombolysis treatment in the region. Results from the SITS-MENA Registry
- 2020
-
Ingår i: International journal of stroke : official journal of the International Stroke Society. - : SAGE Publications. - 1747-4949. ; 15:9, s. 980-987
-
Tidskriftsartikel (refereegranskat)abstract
- Intravenous thrombolysis for acute ischemic stroke in the Middle-East and North African (MENA) countries is still confined to the main urban and university hospitals. This was a prospective observational study to examine outcomes of intravenous thrombolysis-treated stroke patients in the MENA region compared to the non-MENA stroke cohort in the SITS International Registry. Results Of 32,160 patients with ischemic stroke registered using the SITS intravenous thrombolysis protocol between June 2014 and May 2016, 500 (1.6%) were recruited in MENA. Compared to non-MENA (all p < 0.001), median age in MENA was 55 versus 73 years, NIH Stroke Scale score 12 versus 9, onset-to-treatment time 138 versus 155 min and door-to-needle time 54 min versus 64 min. Hypertension was the most reported risk factor, but lower in MENA (51.7 vs. 69.7%). Diabetes was more frequent in MENA (28.5 vs. 20.8%) as well as smoking (20.8 vs. 15.9%). Hyperlipidemia was less observed in MENA (17.6 vs. 29.3%). Functional independence (mRS 0–2) at seven days or discharge was similar (53% vs. 52% in non-MENA), with mortality slightly lower in MENA (2.3% vs. 4.8%). SICH rates by SITS-MOST definition were low (<1.4%) in both groups. Conclusions Intravenous thrombolysis patients in MENA were younger, had more severe strokes and more often diabetes. Although stroke severity was higher in MENA, short-term functional independency and mortality were not worse compared to non-MENA, which could partly be explained by younger age and shorter OTT in MENA. Decreasing the burden of stroke in this young population should be prioritized.
|
|
| 5. |
- Cellini, Andrea, 1991, et al.
(författare)
-
Structural basis of the radical pair state in photolyases and cryptochromes
- 2022
-
Ingår i: Chemical Communications. - : Royal Society of Chemistry (RSC). - 1359-7345 .- 1364-548X. ; , s. 4889-4892
-
Tidskriftsartikel (refereegranskat)abstract
- We present the structure of a photoactivated animal (6-4) photolyase in its radical pair state, captured by serial crystallography. We observe how a conserved asparigine moves towards the semiquinone FAD chromophore and stabilizes it by hydrogen bonding. Several amino acids around the final tryptophan radical rearrange, opening it up to the solvent. The structure explains how the protein environment stabilizes the radical pair state, which is crucial for function of (6-4) photolyases and cryptochromes.
|
|
| 6. |
- Claesson, Elin, 1989, et al.
(författare)
-
The primary structural photoresponse of phytochrome proteins captured by a femtosecond X-ray laser
- 2020
-
Ingår i: eLife. - 2050-084X. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Phytochrome proteins control the growth, reproduction, and photosynthesis of plants, fungi, and bacteria. Light is detected by a bilin cofactor, but it remains elusive how this leads to activation of the protein through structural changes. We present serial femtosecond X-ray crystallographic data of the chromophore-binding domains of a bacterial phytochrome at delay times of 1 ps and 10 ps after photoexcitation. The data reveal a twist of the D-ring, which leads to partial detachment of the chromophore from the protein. Unexpectedly, the conserved so-called pyrrole water is photodissociated from the chromophore, concomitant with movement of the A-ring and a key signaling aspartate. The changes are wired together by ultrafast backbone and water movements around the chromophore, channeling them into signal transduction towards the output domains. We suggest that the observed collective changes are important for the phytochrome photoresponse, explaining the earliest steps of how plants, fungi and bacteria sense red light.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Multamaki, E., et al.
(författare)
-
Comparative analysis of two paradigm bacteriophytochromes reveals opposite functionalities in two-component signaling
- 2021
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Bacterial phytochrome photoreceptors usually belong to two-component signaling systems which transmit environmental stimuli to a response regulator through a histidine kinase domain. Phytochromes switch between red light-absorbing and far-red light-absorbing states. Despite exhibiting extensive structural responses during this transition, the model bacteriophytochrome from Deinococcus radiodurans (DrBphP) lacks detectable kinase activity. Here, we resolve this long-standing conundrum by comparatively analyzing the interactions and output activities of DrBphP and a bacteriophytochrome from Agrobacterium fabrum (Agp1). Whereas Agp1 acts as a conventional histidine kinase, we identify DrBphP as a light-sensitive phosphatase. While Agp1 binds its cognate response regulator only transiently, DrBphP does so strongly, which is rationalized at the structural level. Our data pinpoint two key residues affecting the balance between kinase and phosphatase activities, which immediately bears on photoreception and two-component signaling. The opposing output activities in two highly similar bacteriophytochromes suggest the use of light-controllable histidine kinases and phosphatases for optogenetics. The bacteriophytochrome DrBphP from Deinococcus radiodurans shows high sequence homology to the histidine kinase Agp1 from Agrobacterium fabrum but lacks kinase activity. Here, the authors structurally and biochemically analyse DrBphP and Agp1, showing that DrBphP is a light-activatable phosphatase.
|
|
| 10. |
|
|
