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- Glasbey, JC, et al.
(author)
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- 2021
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swepub:Mat__t
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- Sungnak, W., et al.
(author)
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SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes
- 2020
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In: Nature Medicine. - : Nature Research. - 1078-8956 .- 1546-170X. ; 26:5, s. 681-687
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Journal article (peer-reviewed)abstract
- We investigated SARS-CoV-2 potential tropism by surveying expression of viral entry-associated genes in single-cell RNA-sequencing data from multiple tissues from healthy human donors. We co-detected these transcripts in specific respiratory, corneal and intestinal epithelial cells, potentially explaining the high efficiency of SARS-CoV-2 transmission. These genes are co-expressed in nasal epithelial cells with genes involved in innate immunity, highlighting the cells’ potential role in initial viral infection, spread and clearance. The study offers a useful resource for further lines of inquiry with valuable clinical samples from COVID-19 patients and we provide our data in a comprehensive, open and user-friendly fashion at www.covid19cellatlas.org.
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- Michel, M., et al.
(author)
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Small-molecule activation of OGG1 increases oxidative DNA damage repair by gaining a new function
- 2022
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In: Science. - Stockholm : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 376:6600, s. 1471-1476
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Journal article (peer-reviewed)abstract
- Oxidative DNA damage is recognized by 8-oxoguanine (8-oxoG) DNA glycosylase 1 (OGG1), which excises 8-oxoG, leaving a substrate for apurinic endonuclease 1 (APE1) and initiating repair. Here, we describe a small molecule (TH10785) that interacts with the phenylalanine-319 and glycine-42 amino acids of OGG1, increases the enzyme activity 10-fold, and generates a previously undescribed b,d-lyase enzymatic function. TH10785 controls the catalytic activity mediated by a nitrogen base within its molecular structure. In cells, TH10785 increases OGG1 recruitment to and repair of oxidative DNA damage. This alters the repair process, which no longer requires APE1 but instead is dependent on polynucleotide kinase phosphatase (PNKP1) activity. The increased repair of oxidative DNA lesions with a small molecule may have therapeutic applications in various diseases and aging. © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works
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- Almqvist, Andreas, et al.
(author)
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On lower-dimensional models in lubrication, Part B : Derivation of a Reynolds type of equation for incompressible piezo-viscous fluids
- 2021
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In: Proceedings of the Institution of mechanical engineers. Part J, journal of engineering tribology. - : Sage Publications. - 1350-6501 .- 2041-305X. ; 235:8, s. 1703-1718
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Journal article (peer-reviewed)abstract
- The Reynolds equation is a lower-dimensional model for the pressure in a fluid confined between two adjacent surfaces that move relative to each other. It was originally derived under the assumption that the fluid is incompressible and has constant viscosity. In the existing literature, the lower-dimensional Reynolds equation is often employed as a model for the thin films, which lubricates interfaces in various machine components. For example, in the modelling of elastohydrodynamic lubrication (EHL) in gears and bearings, the pressure dependence of the viscosity is often considered by just replacing the constant viscosity in the Reynolds equation with a given viscosity-pressure relation. The arguments to justify this are heuristic, and in many cases, it is taken for granted that you can do so. This motivated us to make an attempt to formulate and present a rigorous derivation of a lower-dimensional model for the pressure when the fluid has pressure-dependent viscosity. The results of our study are presented in two parts. In Part A, we showed that for incompressible and piezo-viscous fluids it is not possible to obtain a lower-dimensional model for the pressure by just assuming that the film thickness is thin, as it is for incompressible fluids with constant viscosity. Here, in Part B, we present a method for deriving lower-dimensional models of thin-film flow, where the fluid has a pressure-dependent viscosity. The main idea is to rescale the generalised Navier-Stokes equation, which we obtained in Part A based on theory for implicit constitutive relations, so that we can pass to the limit as the film thickness goes to zero. If the scaling is correct, then the limit problem can be used as the dimensionally reduced model for the flow and it is possible to derive a type of Reynolds equation for the pressure.
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- Coleman, M., et al.
(author)
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Hyaluronidase Impairs Neutrophil Function and Promotes Group B Streptococcus Invasion and Preterm Labor in Nonhuman Primates
- 2021
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In: Mbio. - 2150-7511. ; 12:1
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Journal article (peer-reviewed)abstract
- Invasive bacterial infections during pregnancy are a major risk factor for preterm birth, stillbirth, and fetal injury. Group B streptococci (GBS) are Gram-positive bacteria that asymptomatically colonize the lower genital tract but infect the amniotic fluid and induce preterm birth or stillbirth. Experimental models that closely emulate human pregnancy are pivotal for the development of successful strategies to prevent these adverse pregnancy outcomes. Using a unique nonhuman primate model that mimics human pregnancy and informs temporal events surrounding amniotic cavity invasion and preterm labor, we show that the animals inoculated with hyaluronidase (HylB)-expressing GBS consistently exhibited microbial invasion into the amniotic cavity, fetal bacteremia, and preterm labor. Although delayed cytokine responses were observed at the maternal-fetal interface, increased prostaglandin and matrix metalloproteinase levels in these animals likely mediated pre term labor. HylB-proficient GBS dampened reactive oxygen species production and exhibited increased resistance to neutrophils compared to an isogenic mutant. Together, these findings demonstrate how a bacterial enzyme promotes GBS amniotic cavity invasion and preterm labor in a model that closely resembles human pregnancy. IMPORTANCE Group B streptococci (GBS) are bacteria that commonly reside in the female lower genital tract as asymptomatic members of the microbiota. However, during pregnancy, GBS can infect tissues at the maternal-fetal interface, leading to preterm birth, stillbirth, or fetal injury. Understanding how GBS evade host defenses during pregnancy is key to developing improved preventive therapies for these adverse outcomes. In this study, we used a unique nonhuman primate model to show that an enzyme secreted by GBS, hyaluronidase (HylB) promotes bacterial invasion into the amniotic cavity and fetus. Although delayed immune responses were seen at the maternal-fetal interface, animals infected with hyaluronidase-expressing GBS exhibited premature cervical ripening and preterm labor. These observations reveal that HylB is a crucial GBS virulence factor that promotes bacterial invasion and preterm labor in a pregnancy model that closely emulates human pregnancy. Therefore, hyaluronidase inhibitors may be useful in therapeutic strategies against ascending GBS infection.
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