| 1. |
- Nogly, P., et al.
(författare)
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Lipidic cubic phase injector is a viable crystal delivery system for time-resolved serial crystallography
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Serial femtosecond crystallography (SFX) using X-ray free-electron laser sources is an emerging method with considerable potential for time-resolved pump-probe experiments. Here we present a lipidic cubic phase SFX structure of the light-driven proton pump bacteriorhodopsin (bR) to 2.3 angstrom resolution and a method to investigate protein dynamics with modest sample requirement. Time-resolved SFX (TR-SFX) with a pump-probe delay of 1ms yields difference Fourier maps compatible with the dark to M state transition of bR. Importantly, the method is very sample efficient and reduces sample consumption to about 1mg per collected time point. Accumulation of M intermediate within the crystal lattice is confirmed by time-resolved visible absorption spectroscopy. This study provides an important step towards characterizing the complete photocycle dynamics of retinal proteins and demonstrates the feasibility of a sample efficient viscous medium jet for TR-SFX.
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| 2. |
- Abela, D, et al.
(författare)
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The effect of drugs with ion channel-blocking activity on the early embryonic rat heart
- 2010
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Ingår i: Birth defects research. Part B. Developmental and reproductice toxicology. - : Wiley. - 1542-9733 .- 1542-9741. ; 89:5, s. 429-440
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated the effects of a range of pharmaceutical drugs with ion channel-blocking activity on the heart of gestation day 13 rat embryos in vitro. The general hypothesis was that the blockade of the IKr/hERG channel, that is highly important for the normal functioning of the embryonic rat heart, would cause bradycardia and arrhythmia. Concomitant blockade of other channels was expected to modify the effects of hERG blockade. Fourteen drugs with varying degrees of specificity and affinity toward potassium, sodium, and calcium channels were tested over a range of concentrations. The rat embryos were maintained for 2 hr in culture, 1 hr to acclimatize, and 1 hr to test the effect of the drug. All the drugs caused a concentration-dependent bradycardia except nifedipine, which primarily caused a negative inotropic effect eventually stopping the heart. A number of drugs induced arrhythmias and these appeared to be related to either sodium channel blockade, which resulted in a double atrial beat for each ventricular beat, or IKr/hERG blockade, which caused irregular atrial and ventricular beats. However, it is difficult to make a precise prediction of the effect of a drug on the embryonic heart just by looking at the polypharmacological action on ion channels. The results indicate that the use of the tested drugs during pregnancy could potentially damage the embryo by causing periods of hypoxia. In general, the effects on the embryonic heart were only seen at concentrations greater than those likely to occur with normal therapeutic dosing.
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| 3. |
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| 4. |
- Pasin, Chloé, et al.
(författare)
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Sex and gender in infection and immunity : addressing the bottlenecks from basic science to public health and clinical applications
- 2023
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Ingår i: Royal Society Open Science. - 2054-5703. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Although sex and gender are recognized as major determinants of health and immunity, their role is rarely considered in clinical practice and public health. We identified six bottlenecks preventing the inclusion of sex and gender considerations from basic science to clinical practice, precision medicine and public health policies. (i) A terminology-related bottleneck, linked to the definitions of sex and gender themselves, and the lack of consensus on how to evaluate gender. (ii) A data-related bottleneck, due to gaps in sex-disaggregated data, data on trans/non-binary people and gender identity. (iii) A translational bottleneck, limited by animal models and the underrepresentation of gender minorities in biomedical studies. (iv) A statistical bottleneck, with inappropriate statistical analyses and results interpretation. (v) An ethical bottleneck posed by the underrepresentation of pregnant people and gender minorities in clinical studies. (vi) A structural bottleneck, as systemic bias and discriminations affect not only academic research but also decision makers. We specify guidelines for researchers, scientific journals, funding agencies and academic institutions to address these bottlenecks. Following such guidelines will support the development of more efficient and equitable care strategies for all.
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| 5. |
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| 6. |
- Szlachetko, Jakub, et al.
(författare)
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Establishing nonlinearity thresholds with ultraintense X-ray pulses
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- X-ray techniques have evolved over decades to become highly refined tools for a broad range of investigations. Importantly, these approaches rely on X-ray measurements that depend linearly on the number of incident X-ray photons. The advent of X-ray free electron lasers (XFELs) is opening the ability to reach extremely high photon numbers within ultrashort X-ray pulse durations and is leading to a paradigm shift in our ability to explore nonlinear X-ray signals. However, the enormous increase in X-ray peak power is a double-edged sword with new and exciting methods being developed but at the same time well-established techniques proving unreliable. Consequently, accurate knowledge about the threshold for nonlinear X-ray signals is essential. Herein we report an X-ray spectroscopic study that reveals important details on the thresholds for nonlinear X-ray interactions. By varying both the incident X-ray intensity and photon energy, we establish the regimes at which the simplest nonlinear process, two-photon X-ray absorption (TPA), can be observed. From these measurements we can extract the probability of this process as a function of photon energy and confirm both the nature and sub-femtosecond lifetime of the virtual intermediate electronic state.
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