| 1. |
- de Rojas, I., et al.
(författare)
-
Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
|
|
| 2. |
|
|
| 3. |
- Prusti, T., et al.
(författare)
-
The Gaia mission
- 2016
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 595
-
Tidskriftsartikel (refereegranskat)abstract
- Gaia is a cornerstone mission in the science programme of the European Space Agency (ESA). The spacecraft construction was approved in 2006, following a study in which the original interferometric concept was changed to a direct-imaging approach. Both the spacecraft and the payload were built by European industry. The involvement of the scientific community focusses on data processing for which the international Gaia Data Processing and Analysis Consortium (DPAC) was selected in 2007. Gaia was launched on 19 December 2013 and arrived at its operating point, the second Lagrange point of the Sun-Earth-Moon system, a few weeks later. The commissioning of the spacecraft and payload was completed on 19 July 2014. The nominal five-year mission started with four weeks of special, ecliptic-pole scanning and subsequently transferred into full-sky scanning mode. We recall the scientific goals of Gaia and give a description of the as-built spacecraft that is currently (mid-2016) being operated to achieve these goals. We pay special attention to the payload module, the performance of which is closely related to the scientific performance of the mission. We provide a summary of the commissioning activities and findings, followed by a description of the routine operational mode. We summarise scientific performance estimates on the basis of in-orbit operations. Several intermediate Gaia data releases are planned and the data can be retrieved from the Gaia Archive, which is available through the Gaia home page.
|
|
| 4. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
|
|
| 5. |
- Brem, Jürgen, et al.
(författare)
-
Imitation of β-lactam binding enables broad-spectrum metallo-β-lactamase inhibitors
- 2022
-
Ingår i: Nature Chemistry. - : Springer Nature. - 1755-4330 .- 1755-4349. ; 14:1, s. 15-24
-
Tidskriftsartikel (refereegranskat)abstract
- Carbapenems are vital antibiotics, but their efficacy is increasingly compromised by metallo-β-lactamases (MBLs). Here we report the discovery and optimization of potent broad-spectrum MBL inhibitors. A high-throughput screen for NDM-1 inhibitors identified indole-2-carboxylates (InCs) as potential β-lactamase stable β-lactam mimics. Subsequent structure-activity relationship studies revealed InCs as a new class of potent MBL inhibitor, active against all MBL classes of major clinical relevance. Crystallographic studies revealed a binding mode of the InCs to MBLs that, in some regards, mimics that predicted for intact carbapenems, including with respect to maintenance of the Zn(II)-bound hydroxyl, and in other regards mimics binding observed in MBL-carbapenem product complexes. InCs restore carbapenem activity against multiple drug-resistant Gram-negative bacteria and have a low frequency of resistance. InCs also have a good in vivo safety profile, and when combined with meropenem show a strong in vivo efficacy in peritonitis and thigh mouse infection models.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Wild, CP, et al.
(författare)
-
Cancer Prevention Europe
- 2019
-
Ingår i: Molecular oncology. - : Wiley. - 1878-0261 .- 1574-7891. ; 13:3, s. 528-534
-
Tidskriftsartikel (refereegranskat)
|
|
| 9. |
- Buzolin, C. N., et al.
(författare)
-
In situ determination of dissolution kinetics of d-limonene in supercritical carbon dioxide by Raman spectroscopy
- 2017
-
Ingår i: New Journal of Chemistry. - : Royal Society of Chemistry (RSC). - 1144-0546 .- 1369-9261. ; 41:22, s. 13929-13934
-
Tidskriftsartikel (refereegranskat)abstract
- The study of solvation in pressurized systems requires in situ analysis. An optimal spectroscopic technique for such studies would enable the detection of any compound and have resolution enough to differentiate different compounds within a multicomponent mixture. Here we show for the first time that we can follow dissolution kinetics of a model compound, d-limonene, in supercritical carbon dioxide using in situ Raman spectroscopy. Dissolution rate constants were measured at different stirring speeds, temperatures (45 and 55 °C) and amounts of CO2, corresponding to pressures in the range of 8.4 to 17.0 MPa. Dissolution half-lives ranged from 3 min (at 45 °C and 8.4 MPa) up to more than 1 hour (at 55 °C 16.9 MPa). The results indicate that dissolution is mostly controlled by diffusion, while convection did not play a significant role. Dissolution rate constants showed a non-linear inverse relation with diffusivity, while temperature did not influence the dissolution rate constants significantly. Dissolution kinetics is revealed as a significant aspect to consider for the optimization of extraction and separation processes based on supercritical carbon dioxide. Overall, this study offers new insight into solvation phenomena in pressurized fluids.
|
|
| 10. |
- Manez-Espina, L. M., et al.
(författare)
-
Nonreciprocal Huygens' Metasurfaces Based on Bound States in the Continuum
- 2023
-
Ingår i: 17th International Congress on Artificial Materials for Novel Wave Phenomena, Metamaterials 2023. - 9798350332445
-
Konferensbidrag (refereegranskat)abstract
- Magneto-optical effects are typically very weak in the optical spectrum, and there- fore, nonreciprocal devices based on them are very bulky. We demonstrate that optical metasurfaces supporting quasi-bound states in the continuum provide a powerful way for achieving strong nonreciprocal responses in a sub-wavelength geometry. Using the multi-mode temporal coupled-mode theory, we synthesize and analyze a nonreciprocal metasurface with Huygens' meta-atoms based on conventional ferrite materials exhibiting nearly-unity contrast in transmission for circularly polarized light.
|
|
