| 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. |
- Bauer, Georg F., et al.
(författare)
-
Future directions for the concept of salutogenesis : A position article
- 2020
-
Ingår i: Health Promotion International. - : Oxford University Press. - 0957-4824 .- 1460-2245. ; 35:2, s. 187-195
-
Tidskriftsartikel (refereegranskat)abstract
- Aaron Antonovsky advanced the concept of salutogenesis almost four decades ago (Antonovsky, Health, Stress and Coping. Jossey-Bass, San Francisco, CA, 1979; Unravelling the Mystery of Health. Jossey-Bass,San Francisco, CA, 1987). Salutogenesis posits that life experiences shape the sense of coherence (SOC)VC that helps to mobilize resources to cope with stressors and manage tension successfully (determiningone's movement on the health Ease/Dis-ease continuum). Antonovsky considered the three-dimensionalSOC (i.e. comprehensibility, manageability, meaningfulness) as the key answer to his question about theorigin of health. The field of health promotion has adopted the concept of salutogenesis as reflected in theinternational Handbook of Salutogenesis (Mittelmark et al., The Handbook of Salutogenesis. Springer,New York, 2016). However, health promotion mostly builds on the more vague, general salutogenic orientation that implies the need to foster resources and capacities to promote health and wellbeing. Tostrengthen the knowledge base of salutogenesis, the Global Working Group on Salutogenesis (GWG-Sal)of the International Union of Health Promotion and Education produced the Handbook of Salutogenesis.During the creation of the handbook and the regular meetings of the GWG-Sal, the working group identified four key conceptual issues to be advanced: (i) the overall salutogenic model of health; (ii) the SOC concept; (iii) the design of salutogenic interventions and change processes in complex systems; (iv) the application of salutogenesis beyond health sector. For each of these areas, we first highlight Antonovsky'soriginal contribution and then present suggestions for future development. These ideas will help guideGWG-Sal's work to strengthen salutogenesis as a theory base for health promotion.
|
|
| 3. |
- Christopoulos, Arthur, et al.
(författare)
-
THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors.
- 2021
-
Ingår i: British journal of pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 178 Suppl 1
-
Forskningsöversikt (refereegranskat)abstract
- The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
|
|
| 4. |
- Sarmiento Pico, Luis, et al.
(författare)
-
Elucidating the nature of the proton radioactivity and branching ratio on the first proton emitter discovered 53mCo
- 2023
-
Ingår i: Nature Communications. - 2041-1723. ; 14
-
Tidskriftsartikel (refereegranskat)abstract
- The observation of a weak proton-emission branch in the decay of the 3174keV 53mCo isomeric state marked the discovery of proton radioactivity in atomic nuclei in 1970. Here we show, based on the partial half-lives and the decay energies of the possible proton-emission branches, that the exceptionally high angular momentum barriers, lp = 9 and lp = 7, play a key role in hindering the proton radioactivity from 53mCo, making them very challenging to observe and calculate. Indeed, experiments had to wait decades for significant advances in accelerator facilities and multi-faceted state-of-the-art decay stations to gain full access to all observables. Combining data taken with the TASISpec decay station at the Accelerator Laboratory of the University of Jyväskylä, Finland, and the ACTAR TPC device on LISE3 at GANIL, France, we measured their branching ratios as bp1 = 1.3(1)% and bp2 = 0.025(4)%. These results were compared to cutting-edge shell-model and barrier penetration calculations. This description reproduces the order of magnitude of the branching ratios and partial half-lives, despite their very small spectroscopic factors.
|
|
| 5. |
- Walker, Anthony P., et al.
(författare)
-
Integrating the evidence for a terrestrial carbon sink caused by increasing atmospheric CO2
- 2021
-
Ingår i: New Phytologist. - : John Wiley & Sons. - 0028-646X .- 1469-8137. ; 229:5, s. 2413-2445
-
Tidskriftsartikel (refereegranskat)abstract
- Atmospheric carbon dioxide concentration ([CO2]) is increasing, which increases leaf‐scale photosynthesis and intrinsic water‐use efficiency. These direct responses have the potential to increase plant growth, vegetation biomass, and soil organic matter; transferring carbon from the atmosphere into terrestrial ecosystems (a carbon sink). A substantial global terrestrial carbon sink would slow the rate of [CO2] increase and thus climate change. However, ecosystem CO2 responses are complex or confounded by concurrent changes in multiple agents of global change and evidence for a [CO2]‐driven terrestrial carbon sink can appear contradictory. Here we synthesize theory and broad, multidisciplinary evidence for the effects of increasing [CO2] (iCO2) on the global terrestrial carbon sink. Evidence suggests a substantial increase in global photosynthesis since pre‐industrial times. Established theory, supported by experiments, indicates that iCO2 is likely responsible for about half of the increase. Global carbon budgeting, atmospheric data, and forest inventories indicate a historical carbon sink, and these apparent iCO2 responses are high in comparison to experiments and predictions from theory. Plant mortality and soil carbon iCO2 responses are highly uncertain. In conclusion, a range of evidence supports a positive terrestrial carbon sink in response to iCO2, albeit with uncertain magnitude and strong suggestion of a role for additional agents of global change.
|
|
| 6. |
- Wright, Gillian, et al.
(författare)
-
The Mid-infrared Instrument for JWST and Its In-flight Performance
- 2023
-
Ingår i: Publications of the Astronomical Society of the Pacific. - 0004-6280 .- 1538-3873. ; 135:1046
-
Tidskriftsartikel (refereegranskat)abstract
- The Mid-Infrared Instrument (MIRI) extends the reach of the James Webb Space Telescope (JWST) to 28.5 μm. It provides subarcsecond-resolution imaging, high sensitivity coronagraphy, and spectroscopy at resolutions of λ/Δλ ∼ 100-3500, with the high-resolution mode employing an integral field unit to provide spatial data cubes. The resulting broad suite of capabilities will enable huge advances in studies over this wavelength range. This overview describes the history of acquiring this capability for JWST. It discusses the basic attributes of the instrument optics, the detector arrays, and the cryocooler that keeps everything at approximately 7 K. It gives a short description of the data pipeline and of the instrument performance demonstrated during JWST commissioning. The bottom line is that the telescope and MIRI are both operating to the standards set by pre-launch predictions, and all of the MIRI capabilities are operating at, or even a bit better than, the level that had been expected. The paper is also designed to act as a roadmap to more detailed papers on different aspects of MIRI.
|
|
| 7. |
- Bulman, Zackery P., et al.
(författare)
-
Research priorities towards precision antibiotic therapy to improve patient care
- 2022
-
Ingår i: LANCET MICROBE. - : Elsevier. - 2666-5247. ; 3:10, s. e795-e802
-
Tidskriftsartikel (refereegranskat)abstract
- Antibiotic resistance presents an incessant threat to our drug armamentarium that necessitates novel approaches to therapy. Over the past several decades, investigation of pharmacokinetic and pharmacodynamic (PKPD) principles has substantially improved our understanding of the relationships between the antibiotic, pathogen, and infected patient. However, crucial gaps in our understanding of the pharmacology of antibacterials and their optimal use in the care of patients continue to exist; simply attaining antibiotic exposures that are considered adequate based on traditional targets can still result in treatment being unsuccessful and resistance proliferation for some infections. It is this salient paradox that points to key future directions for research in antibiotic therapeutics. This Personal View discusses six priority areas for antibiotic pharmacology research: (1) antibiotic-pathogen interactions, (2) antibiotic targets for combination therapy, (3) mechanistic models that describe the time-course of treatment response, (4) understanding and modelling of host response to infection, (5) personalised medicine through therapeutic drug management, and (6) application of these principles to support development of novel therapies. Innovative approaches that enhance our understanding of antibiotic pharmacology and facilitate more accurate predictions of treatment success, coupled with traditional pharmacology research, can be applied at the population level and to individual patients to improve outcomes.
|
|
| 8. |
- Falster, Daniel, et al.
(författare)
-
AusTraits, a curated plant trait database for the Australian flora
- 2021
-
Ingår i: Scientific Data. - : Nature Portfolio. - 2052-4463. ; 8:1
-
Tidskriftsartikel (refereegranskat)abstract
- We introduce the AusTraits database - a compilation of values of plant traits for taxa in the Australian flora (hereafter AusTraits). AusTraits synthesises data on 448 traits across 28,640 taxa from field campaigns, published literature, taxonomic monographs, and individual taxon descriptions. Traits vary in scope from physiological measures of performance (e.g. photosynthetic gas exchange, water-use efficiency) to morphological attributes (e.g. leaf area, seed mass, plant height) which link to aspects of ecological variation. AusTraits contains curated and harmonised individual- and species-level measurements coupled to, where available, contextual information on site properties and experimental conditions. This article provides information on version 3.0.2 of AusTraits which contains data for 997,808 trait-by-taxon combinations. We envision AusTraits as an ongoing collaborative initiative for easily archiving and sharing trait data, which also provides a template for other national or regional initiatives globally to fill persistent gaps in trait knowledge.
|
|
| 9. |
- Gluud, Maria, et al.
(författare)
-
MicroRNAs in the Pathogenesis, Diagnosis, Prognosis and Targeted Treatment of Cutaneous T-Cell Lymphomas
- 2020
-
Ingår i: Cancers. - : MDPI. - 2072-6694. ; 12:5
-
Forskningsöversikt (refereegranskat)abstract
- Cutaneous T-cell lymphoma (CTCL) represents a heterogeneous group of potentially devastating primary skin malignancies. Despite decades of intense research efforts, the pathogenesis is still not fully understood. In the early stages, both clinical and histopathological diagnosis is often difficult due to the ability of CTCL to masquerade as benign skin inflammatory dermatoses. Due to a lack of reliable biomarkers, it is also difficult to predict which patients will respond to therapy or progress towards severe recalcitrant disease. In this review, we discuss recent discoveries concerning dysregulated microRNA (miR) expression and putative pathological roles of oncogenic and tumor suppressive miRs in CTCL. We also focus on the interplay between miRs, histone deacetylase inhibitors, and oncogenic signaling pathways in malignant T cells as well as the impact of miRs in shaping the inflammatory tumor microenvironment. We highlight the potential use of miRs as diagnostic and prognostic markers, as well as their potential as therapeutic targets. Finally, we propose that the combined use of miR-modulating compounds with epigenetic drugs may provide a novel avenue for boosting the clinical efficacy of existing anti-cancer therapies in CTCL.
|
|
| 10. |
- Grant, Sierra L., et al.
(författare)
-
MINDS. The Detection of 13 CO 2 with JWST-MIRI Indicates Abundant CO 2 in a Protoplanetary Disk
- 2023
-
Ingår i: Astrophysical Journal Letters. - 2041-8213 .- 2041-8205. ; 947:1
-
Tidskriftsartikel (refereegranskat)abstract
- We present JWST-MIRI Medium Resolution Spectrometer (MRS) spectra of the protoplanetary disk around the low-mass T Tauri star GW Lup from the MIRI mid-INfrared Disk Survey Guaranteed Time Observations program. Emission from 12CO213CO2, H2O, HCN, C2H2, and OH is identified with 13CO2 being detected for the first time in a protoplanetary disk. We characterize the chemical and physical conditions in the inner few astronomical units of the GW Lup disk using these molecules as probes. The spectral resolution of JWST-MIRI MRS paired with high signal-to-noise data is essential to identify these species and determine their column densities and temperatures. The Q branches of these molecules, including those of hot bands, are particularly sensitive to temperature and column density. We find that the 12CO2 emission in the GW Lup disk is coming from optically thick emission at a temperature of ∼400 K. 13CO2 is optically thinner and based on a lower temperature of ∼325 K, and thus may be tracing deeper into the disk and/or a larger emitting radius than 12CO2. The derived N CO 2 / N H 2 O ratio is orders of magnitude higher than previously derived for GW Lup and other targets based on Spitzer-InfraRed-Spectrograph data. This high column density ratio may be due to an inner cavity with a radius in between the H2O and CO2 snowlines and/or an overall lower disk temperature. This paper demonstrates the unique ability of JWST to probe inner disk structures and chemistry through weak, previously unseen molecular features.
|
|
