| 1. |
- Gapińska, Marta, et al.
(author)
-
Structure-functional characterization of Lactococcus AbiA phage defense system
- 2024
-
In: Nucleic Acids Research. - 1362-4962. ; 52:8, s. 4723-4738
-
Journal article (peer-reviewed)abstract
- Bacterial reverse transcriptases (RTs) are a large and diverse enzyme family. AbiA, AbiK and Abi-P2 are abortive infection system (Abi) RTs that mediate defense against bacteriophages. What sets Abi RTs apart from other RT enzymes is their ability to synthesize long DNA products of random sequences in a template- and primer-independent manner. Structures of AbiK and Abi-P2 representatives have recently been determined, but there are no structural data available for AbiA. Here, we report the crystal structure of Lactococcus AbiA polymerase in complex with a single-stranded polymerization product. AbiA comprises three domains: an RT-like domain, a helical domain that is typical for Abi polymerases, and a higher eukaryotes and prokaryotes nucleotide-binding (HEPN) domain that is common for many antiviral proteins. AbiA forms a dimer that distinguishes it from AbiK and Abi-P2, which form trimers/hexamers. We show the DNA polymerase activity of AbiA in an in vitro assay and demonstrate that it requires the presence of the HEPN domain which is enzymatically inactive. We validate our biochemical and structural results in vivo through bacteriophage infection assays. Finally, our in vivo results suggest that AbiA-mediated phage defense may not rely on AbiA-mediated cell death.
|
|
| 2. |
- Grodzińska-Jurczak, Małgorzata, et al.
(author)
-
Environmental choices vs. covid-19 pandemic fear – plastic governance re-assessment
- 2020
-
In: Society Register. - : Adam Mickiewicz University in Poznan. - 2544-5502. ; 4:2, s. 49-66
-
Journal article (peer-reviewed)abstract
- Alarming plastic production growth worldwide reinforces the public debate about the prevailing environmental crisis, whereby single-use-plastic (SUP) items are considered as by far the most harmful to the environment and public health. Accordingly, European environmental policy aims at eliminating SUP. Recently, we presented a model of plastic governance that derives from a circular economy approach identifying and taking into consideration perspectives of different actors in the plastic governance, such as producers, wholesalers, shop keepers, consumers, citizen scientists, and academia. Our results illustrate that the vast majority of stakeholders cared for the natural environment and understood the need to phase out SUP from the global economy. We proposed that a knowledge brokerage, undertaken by scientists via means of citizen science, as the most effective method to implement elimination policy, as it provides stakeholders with knowledge on why and how to handle SUP issues. However, at the time of the global COVID-19 pandemic, a plastic governance model required a re-assessment. The perceived role of SUP has changed, as it reflects the health emergency. Namely, due to the health safety reasons stakeholders and consumers are requesting even more SUP than previously. Following up on our data gathered prior to the pandemic, we suggest that under the new circumstances health concerns outweigh the environmental concerns being determined by a shift in the value hierarchization. The paper discusses preliminary results.
|
|
| 3. |
- Schunk, Stefan J., et al.
(author)
-
Genetically determined NLRP3 inflammasome activation associates with systemic inflammation and cardiovascular mortality
- 2021
-
In: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:18, s. 1742-1756
-
Journal article (peer-reviewed)abstract
- AimsInflammation plays an important role in cardiovascular disease (CVD) development. The NOD-like receptor protein-3 (NLRP3) inflammasome contributes to the development of atherosclerosis in animal models. Components of the NLRP3 inflammasome pathway such as interleukin-1β can therapeutically be targeted. Associations of genetically determined inflammasome-mediated systemic inflammation with CVD and mortality in humans are unknown.Methods and resultsWe explored the association of genetic NLRP3 variants with prevalent CVD and cardiovascular mortality in 538 167 subjects on the individual participant level in an explorative gene-centric approach without performing multiple testing. Functional relevance of single-nucleotide polymorphisms on NLRP3 inflammasome activation has been evaluated in monocyte-enriched peripheral blood mononuclear cells (PBMCs). Genetic analyses identified the highly prevalent (minor allele frequency 39.9%) intronic NLRP3 variant rs10754555 to affect NLRP3 gene expression. rs10754555 carriers showed significantly higher C-reactive protein and serum amyloid A plasma levels. Carriers of the G allele showed higher NLRP3 inflammasome activation in isolated human PBMCs. In carriers of the rs10754555 variant, the prevalence of coronary artery disease was significantly higher as compared to non-carriers with a significant interaction between rs10754555 and age. Importantly, rs10754555 carriers had significantly higher risk for cardiovascular mortality during follow-up. Inflammasome inducers (e.g. urate, triglycerides, apolipoprotein C3) modulated the association between rs10754555 and mortality.ConclusionThe NLRP3 intronic variant rs10754555 is associated with increased systemic inflammation, inflammasome activation, prevalent coronary artery disease, and mortality. This study provides evidence for a substantial role of genetically driven systemic inflammation in CVD and highlights the NLRP3 inflammasome as a therapeutic target.
|
|
| 4. |
- Teo, Kevin, et al.
(author)
-
rs641738C>T near MBOAT7 is associated with liver fat, ALT, and fibrosis in NAFLD: a meta-analysis.
- 2021
-
In: Journal of hepatology. - : Elsevier BV. - 1600-0641 .- 0168-8278. ; 74:1, s. 20-30
-
Journal article (peer-reviewed)abstract
- A common genetic variant near MBOAT7 (rs641738C>T) has been previously associated with hepatic fat and advanced histology in non-alcoholic fatty liver disease (NAFLD), however, these findings have not been consistently replicated in the literature. We aimed to establish whether rs641738C>T is a risk factor across the spectrum of NAFLD and characterize its role in the regulation of related metabolic phenotypes through meta-analysis.We performed meta-analysis of studies with data on the association between rs641738C>T genotype and: liver fat, NAFLD histology, and serum ALT, lipids, or insulin. These included directly genotyped studies and population-level data from genome-wide association studies (GWAS). We performed random effects meta-analysis using recessive, additive, and dominant genetic models.Data from 1,066,175 participants (9,688 with liver biopsies) across 42 studies were included in the meta-analysis. rs641738C>T was associated with higher liver fat on CT/MRI (+0.03 standard deviations [95% CI: 0.02 - 0.05], pz=4.8x10-5) and diagnosis of NAFLD (OR 1.17 [95% CI 1.05 - 1.3], pz=0.003) in Caucasian adults. The variant was also positively associated with presence of advanced fibrosis (OR 1.22 [95% CI: 1.03 - 1.45], pz=0.021) in Caucasian adults using a recessive model of inheritance (CC+CT vs. TT). Meta-analysis of data from previous GWAS found the variant to be associated with higher ALT (pz=0.002) and lower serum triglycerides (pz=1.5x10-4). rs641738C>T was not associated with fasting insulin and no effect was observed in children with NAFLD.Our study validates rs641738C>T near MBOAT7 as a risk factor for the presence and severity of NAFLD in individuals of European descent.
|
|
