| 1. |
- Isaksson, Frida, et al.
(author)
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Evaluating the Use of Alternative Normalization Approaches on SARS-CoV-2 Concentrations in Wastewater: Experiences from Two Catchments in Northern Sweden
- 2022
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In: Environments. - : MDPI. - 2076-3298. ; 9:3
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Journal article (peer-reviewed)abstract
- The detection of SARS-CoV-2 RNA fragments in feces has paved the way for wastewater-based epidemiology to contribute to COVID-19 mitigation measures, with its use in a public health context still under development. As a way to facilitate data comparison, this paper explores the impact of using alternative normalization approaches (wastewater treatment plant (WWTP) flow, population size estimates (derived using total nitrogen (TN), total phosphorus (TP) and census data) and pepper mild mottle virus (PMMoV)) on the relationship between viral wastewater data and clinical case numbers. Influent wastewater samples were collected at two WWTPs in Luleå, northern Sweden, between January and March 2021. TN and TP were determined upon sample collection, with RNA analysis undertaken on samples after one freeze–thaw cycle. The strength of the correlation between normalization approaches and clinical cases differed between WWTPs (r ≤ 0.73 or r ≥ 0.78 at the larger WWTP and r ≤ 0.23 or r ≥ 0.43 at the smaller WWTP), indicating that the use of wastewater as an epidemiological tool is context-dependent. Depending on the normalization approach utilized, time-shifted analyses imply that wastewater data on SARS-CoV-2 RNA pre-dated a rise in clinical cases by 0–2 and 5–8 days, for the lager and smaller WWTPs, respectively. SARS-CoV-2 viral loads normalized to the population or PMMoV better reflect the number of clinical cases when comparing wastewater data between sewer catchments.
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| 2. |
- Sanna, Adriana, et al.
(author)
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DNA promoter hypermethylation of melanocyte lineage genes determines melanoma phenotype
- 2022
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In: JCI Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 7:19
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Journal article (peer-reviewed)abstract
- Cellular stress contributes to the capacity of melanoma cells to undergo phenotype switching into highly migratory and drug tolerant dedifferentiated states. Such dedifferentiated melanoma cell states are marked by loss of melanocyte specific gene expression and increase of mesenchymal markers. Two crucial transcription factors, MITF and SOX10, important in melanoma development and progression have been implicated in this process. In this study we describe that loss of MITF is associated with a distinct transcriptional program, MITF promoter hypermethylation and poor patient survival in metastatic melanoma. From a comprehensive collection of melanoma cell lines, we observed that MITF methylated cultures were subdivided in two distinct subtypes. Examining mRNA levels of neural crest associated genes we found that one subtype had lost the expression of several lineage genes including SOX10. Intriguingly, SOX10 loss was associated with SOX10 gene promoter hypermethylation and distinct phenotypic and metastatic properties. Depletion of SOX10 in MITF methylated melanoma cells using CRISPR/Cas9 confirmed these findings. In conclusion, this study describes the significance of melanoma state and the underlying functional properties explaining the aggressiveness of such states.
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| 3. |
- Sanna, Adriana, et al.
(author)
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DNA promoter hypermethylation of melanocyte lineage genes determines melanoma phenotype.
- 2022
-
In: JCI insight. - : The American Society for Clinical Investigation. - 2379-3708. ; 7:19
-
Journal article (peer-reviewed)abstract
- Cellular stress contributes to the capacity of melanoma cells to undergo phenotype switching into highly migratory and drug-tolerant dedifferentiated states. Such dedifferentiated melanoma cell states are marked by loss of melanocyte-specific gene expression and increase of mesenchymal markers. Two crucial transcription factors, microphthalmia-associated transcription factor (MITF) and SRY-box transcription factor 10 (SOX10), important in melanoma development and progression, have been implicated in this process. In this study we describe that loss of MITF is associated with a distinct transcriptional program, MITF promoter hypermethylation, and poor patient survival in metastatic melanoma. From a comprehensive collection of melanoma cell lines, we observed that MITF-methylated cultures were subdivided in 2 distinct subtypes. Examining mRNA levels of neural crest-associated genes, we found that 1 subtype had lost the expression of several lineage genes, including SOX10. Intriguingly, SOX10 loss was associated with SOX10 gene promoter hypermethylation and distinct phenotypic and metastatic properties. Depletion of SOX10 in MITF-methylated melanoma cells using CRISPR/Cas9 supported these findings. In conclusion, this study describes the significance of melanoma state and the underlying functional properties explaining the aggressiveness of such states.
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