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- Wacker, A, et al.
(författare)
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Secondary structure determination of conserved SARS-CoV-2 RNA elements by NMR spectroscopy
- 2020
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Ingår i: Nucleic acids research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 48:22, s. 12415-12435
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Tidskriftsartikel (refereegranskat)abstract
- The current pandemic situation caused by the Betacoronavirus SARS-CoV-2 (SCoV2) highlights the need for coordinated research to combat COVID-19. A particularly important aspect is the development of medication. In addition to viral proteins, structured RNA elements represent a potent alternative as drug targets. The search for drugs that target RNA requires their high-resolution structural characterization. Using nuclear magnetic resonance (NMR) spectroscopy, a worldwide consortium of NMR researchers aims to characterize potential RNA drug targets of SCoV2. Here, we report the characterization of 15 conserved RNA elements located at the 5′ end, the ribosomal frameshift segment and the 3′-untranslated region (3′-UTR) of the SCoV2 genome, their large-scale production and NMR-based secondary structure determination. The NMR data are corroborated with secondary structure probing by DMS footprinting experiments. The close agreement of NMR secondary structure determination of isolated RNA elements with DMS footprinting and NMR performed on larger RNA regions shows that the secondary structure elements fold independently. The NMR data reported here provide the basis for NMR investigations of RNA function, RNA interactions with viral and host proteins and screening campaigns to identify potential RNA binders for pharmaceutical intervention.
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- Schnieders, R, et al.
(författare)
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1H, 13C and 15N chemical shift assignment of the stem-loop 5a from the 5'-UTR of SARS-CoV-2
- 2021
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Ingår i: Biomolecular NMR assignments. - : Springer Science and Business Media LLC. - 1874-270X .- 1874-2718. ; 15:1, s. 203-211
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Tidskriftsartikel (refereegranskat)abstract
- The SARS-CoV-2 (SCoV-2) virus is the causative agent of the ongoing COVID-19 pandemic. It contains a positive sense single-stranded RNA genome and belongs to the genus of Betacoronaviruses. The 5′- and 3′-genomic ends of the 30 kb SCoV-2 genome are potential antiviral drug targets. Major parts of these sequences are highly conserved among Betacoronaviruses and contain cis-acting RNA elements that affect RNA translation and replication. The 31 nucleotide (nt) long highly conserved stem-loop 5a (SL5a) is located within the 5′-untranslated region (5′-UTR) important for viral replication. SL5a features a U-rich asymmetric bulge and is capped with a 5′-UUUCGU-3′ hexaloop, which is also found in stem-loop 5b (SL5b). We herein report the extensive 1H, 13C and 15N resonance assignment of SL5a as basis for in-depth structural studies by solution NMR spectroscopy.
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| 5. |
- Bastian, Z., et al.
(författare)
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Retrofit with Passive House components
- 2022
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Ingår i: Energy Efficiency. - : Springer Science and Business Media LLC. - 1570-646X .- 1570-6478. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- The Passive House is a performance-based efficiency standard for new buildings. The factors that lead to very low heating and cooling demands include compact shape, favourable orientation and size of windows, good insulation, optimised thermal bridges, high-performance glazing, insulated window frames, airtightness, mechanical ventilation with heat or energy recovery, cool colours and solar control. Many of these components can also be used in retrofits of existing buildings, although Passive House levels of energy efficiency are often hard to achieve in renovation. EnerPHit is a voluntary standard for high-efficiency retrofits that is based on the use of typical Passive House components. It pursues economic efficiency and simultaneously addresses thermal comfort, indoor air quality, climate protection and hygrothermal performance. This paper is the first fully comprehensive publication of the foundations upon which the EnerPHit criteria were developed. Furthermore, we present five EnerPHit example buildings, including energy consumption data, costs and solutions for the challenges that arose in the practical implementation: a multifamily residence in Frankfurt, Germany, two row houses in Hereford, the UK and New York, USA, a school in Innsbruck, Austria, and a high-rise in Gothenburg, Sweden. Where measured performance data are available, they confirm very low energy consumptions of the refurbishments. The corresponding investments can be profitable.
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| 6. |
- Brusaferri, Ludovica, et al.
(författare)
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Neuroimmune activation and increased brain aging in chronic pain patients after the COVID-19 pandemic onset
- 2024
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Ingår i: Brain, Behavior, and Immunity. - 0889-1591 .- 1090-2139. ; 116, s. 259-266
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic has exerted a global impact on both physical and mental health, and clinical populations have been disproportionally affected. To date, however, the mechanisms underlying the deleterious effects of the pandemic on pre-existing clinical conditions remain unclear. Here we investigated whether the onset of the pandemic was associated with an increase in brain/blood levels of inflammatory markers and MRI-estimated brain age in patients with chronic low back pain (cLBP), irrespective of their infection history. A retrospective cohort study was conducted on 56 adult participants with cLBP (28 ‘Pre-Pandemic’, 28 ‘Pandemic’) using integrated Positron Emission Tomography/ Magnetic Resonance Imaging (PET/MRI) and the radioligand [11C]PBR28, which binds to the neuroinflammatory marker 18 kDa Translocator Protein (TSPO). Image data were collected between November 2017 and January 2020 (‘Pre-Pandemic’ cLBP) or between August 2020 and May 2022 (‘Pandemic’ cLBP). Compared to the Pre-Pandemic group, the Pandemic patients demonstrated widespread and statistically significant elevations in brain TSPO levels (P =.05, cluster corrected). PET signal elevations in the Pandemic group were also observed when 1) excluding 3 Pandemic subjects with a known history of COVID infection, or 2) using secondary outcome measures (volume of distribution -VT- and VT ratio - DVR) in a smaller subset of participants. Pandemic subjects also exhibited elevated serum levels of inflammatory markers (IL-16; P <.05) and estimated BA (P <.0001), which were positively correlated with [11C]PBR28 SUVR (r's ≥ 0.35; P's < 0.05). The pain interference scores, which were elevated in the Pandemic group (P <.05), were negatively correlated with [11C]PBR28 SUVR in the amygdala (r = −0.46; P<.05). This work suggests that the pandemic outbreak may have been accompanied by neuroinflammation and increased brain age in cLBP patients, as measured by multimodal imaging and serum testing. This study underscores the broad impact of the pandemic on human health, which extends beyond the morbidity solely mediated by the virus itself.
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