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- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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- Yaghootkar, Hanieh, et al.
(författare)
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Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity
- 2020
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 69:12, s. 2806-2818
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Tidskriftsartikel (refereegranskat)abstract
- Leptin influences food intake by informing the brain about the status of body fat stores. Rare LEP mutations associated with congenital leptin deficiency cause severe early-onset obesity that can be mitigated by administering leptin. However, the role of genetic regulation of leptin in polygenic obesity remains poorly understood. We performed an exome-based analysis in up to 57,232 individuals of diverse ancestries to identify genetic variants that influence adiposity-adjusted leptin concentrations. We identify five novel variants, including four missense variants, in LEP, ZNF800, KLHL31, and ACTL9, and one intergenic variant near KLF14. The missense variant Val94Met (rs17151919) in LEP was common in individuals of African ancestry only, and its association with lower leptin concentrations was specific to this ancestry (P = 2 × 10-16, n = 3,901). Using in vitro analyses, we show that the Met94 allele decreases leptin secretion. We also show that the Met94 allele is associated with higher BMI in young African-ancestry children but not in adults, suggesting that leptin regulates early adiposity.
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| 7. |
- Axfors, Cathrine, et al.
(författare)
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Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials
- 2021
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Ingår i: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 21:1
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Forskningsöversikt (refereegranskat)abstract
- Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
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- Burraco, Pablo, et al.
(författare)
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Climate change and ageing in ectotherms
- 2020
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Ingår i: Global Change Biology. - : WILEY. - 1354-1013 .- 1365-2486. ; 26:10, s. 5371-5381
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Tidskriftsartikel (refereegranskat)abstract
- Human activity is changing climatic conditions at an unprecedented rate. The impact of these changes may be especially acute on ectotherms since they have limited capacities to use metabolic heat to maintain their body temperature. An increase in temperature is likely to increase the growth rate of ectothermic animals, and may also induce thermal stress via increased exposure to heat waves. Fast growth and thermal stress are metabolically demanding, and both factors can increase oxidative damage to essential biomolecules, accelerating the rate of ageing. Here, we explore the potential impact of global warming on ectotherm ageing through its effects on reactive oxygen species production, oxidative damage, and telomere shortening, at the individual and intergenerational levels. Most evidence derives primarily from vertebrates, although the concepts are broadly applicable to invertebrates. We also discuss candidate mechanisms that could buffer ectotherms from the potentially negative consequences of climate change on ageing. Finally, we suggest some potential applications of the study of ageing mechanisms for the implementation of conservation actions. We find a clear need for more ecological, biogeographical, and evolutionary studies on the impact of global climate change on patterns of ageing rates in wild populations of ectotherms facing warming conditions. Understanding the impact of warming on animal life histories, and on ageing in particular, needs to be incorporated into the design of measures to preserve biodiversity to improve their effectiveness.
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- Comina Bellido, German
(författare)
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Autonomous Lab-on-a-chip: solutions and fast prototyping tools
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis, solutions for the development of autonomous Lab-on-a-chip (LOC), and 3D printing for fast prototyping of LOC devices are investigated. Lab-on-a-chip devices integrate analytical systems and conditioning processes in a compact package. Small sample volume, disposability, ability to perform complex analysis and performance comparable to classical instrumentation are characteristics that make LOCs excellent candidates for biomedical applications, environmental monitoring and food analysis. Classical LOC configurations usually require additional elements such as pumps, valves, fluidics interface connectors, and even pneumatic control to operate. Also, in most cases, a computer-capable device, or standalone control system, is needed in connection with the measurements. Autonomous LOCs avoid the use of additional components, as they are designed to integrate all necessary parts in one design. Cell phones are the most wide spread computer capable devices, and the advantage to exploit them as analytical instruments is obvious. They have been used in connection with microfluidic LOC measurements, typically using accessory dongles. To connect to the LOCs, in some cases, even permanent modifications of the phones were required. In this thesis, direct coupling to cell phone readout, without accessories beyond the LOC, has been investigated. Autonomous LOC development demands extensive time and resources for prototype optimization. Classical LOC fabrication methods, which are based on lithographic microfabrication, require special equipment and facilities. Additionally, the fabrication of 3D structures require multiple fabrication steps with numerous intermediate alignment. In this thesis, commercial-grade, low-cost 3D printers have been investigated as fast LOC prototyping platforms. The printers (Miicraft® DLP-3D printer and Formlabs Inc. Form+1) are based on Stereo Lithography (SLA). In this additive fabrication technique, a 3D computer model of the LOC is designed. Later, the 3D model is sliced in 2D patterns along the height of the design, and each of the 2D patterns is projected through the printer transparent tank bottom, which contains a liquid photocurable resin. Each exposure cures a thin layer of the resin, and the procedure is repeated adding layer after layer until the 3D printout is completed. With this technique it was possible to obtain real 3D LOC structures with unlimited number of 3D features in one step, within the hour, and at low-cost for prototyping, which constitutes a superb tool for fast and affordable sophistication of LOC architecture. The process was extended in this thesis to another area of complex and costly development: the manufacture of optical components. It was shown that optical components with arbitrary geometry could be obtained within the hour and typically for less than 1€/prototype. The first use of the technique was to produce templates for classical LOCs of polydimethylsiloxane (PDMS) on glass. The procedure was the first, to our knowledge, implemented with consumer grade printers, and included a demonstration of template fabrication for the development of a multilayer PDMS-LOC for colorimetric detection of glucose. The technique then evolved to the complete replacement of the PDMS stage, by conceiving the LOC architecture as a single monolithic printout. This concept was coined Unibody LOC (ULOC) and was used in this thesis for the development of all the autonomous Lab on a Chip solutions. Numerous solutions towards autonomous LOCs were developed such as: multidimensional adaptors that connect for example 1.6mm diameter tubing directly to 50μm wide microfluidic channels, several on plane and multilayer mixers, hybrid ULOC with paper channels, finger-pumps, check-valves, optical couplers and 3D printed optics. Time-dependent optical response bio-chemical reactions were identified as key to implement the link between autonomous LOC with cell phones without other accessories, and relying on ambient light as illumination. Such approach improves the analytical resolution of a colorimetric measurement using essentially the same camera. Finally, all those solutions were integrated to develop a chemical sensing interface for universal cell phone readout, and a 3D printed device for quantitative enzymatic detection using cell phones.
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- Hendriks, Kasper P., et al.
(författare)
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Global Brassicaceae phylogeny based on filtering of 1,000-gene dataset
- 2023
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Ingår i: Current Biology. - : Elsevier. - 0960-9822 .- 1879-0445. ; 33:19, s. 4052-4068
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Tidskriftsartikel (refereegranskat)abstract
- The mustard family (Brassicaceae) is a scientifically and economically important family, containing the model plant Arabidopsis thaliana and numerous crop species that feed billions worldwide. Despite its relevance, most phylogenetic trees of the family are incompletely sampled and often contain poorly supported branches. Here, we present the most complete Brassicaceae genus-level family phylogenies to date (Bras-sicaceae Tree of Life or BrassiToL) based on nuclear (1,081 genes, 319 of the 349 genera; 57 of the 58 tribes) and plastome (60 genes, 265 genera; all tribes) data. We found cytonuclear discordance between the two, which is likely a result of rampant hybridization among closely and more distantly related lineages. To eval-uate the impact of such hybridization on the nuclear phylogeny reconstruction, we performed five different gene sampling routines, which increasingly removed putatively paralog genes. Our cleaned subset of 297 genes revealed high support for the tribes, whereas support for the main lineages (supertribes) was moder-ate. Calibration based on the 20 most clock-like nuclear genes suggests a late Eocene to late Oligocene origin of the family. Finally, our results strongly support a recently published new family classification, dividing the family into two subfamilies (one with five supertribes), together representing 58 tribes. This includes five recently described or re-established tribes, including Arabidopsideae, a monogeneric tribe accommodating Arabidopsis without any close relatives. With a worldwide community of thousands of researchers working on Brassicaceae and its diverse members, our new genus-level family phylogeny will be an indispensable tool for studies on biodiversity and plant biology.
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