| 1. |
- Abbafati, Cristiana, et al.
(författare)
-
- 2020
-
Tidskriftsartikel (refereegranskat)
|
|
| 2. |
- Suiter, Chase C., et al.
(författare)
-
Massively parallel variant characterization identifies NUDT15 alleles associated with thiopurine toxicity
- 2020
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 117:10, s. 5394-5401
-
Tidskriftsartikel (refereegranskat)abstract
- As a prototype of genomics-guided precision medicine, individualized thiopurine dosing based on pharmacogenetics is a highly effective way to mitigate hematopoietic toxicity of this class of drugs. Recently, NUDT15 deficiency was identified as a genetic cause of thiopurine toxicity, and NUDT15-informed preemptive dose reduction was quickly adopted in clinical settings. To exhaustively identify pharmacogenetic variants in this gene, we developed massively parallel NUDT15 function assays to determine the variants' effect on protein abundance and thiopurine cytotoxicity. Of the 3,097 possible missense variants, we characterized the abundance of 2,922 variants and found 54 hotspot residues at which variants resulted in complete loss of protein stability. Analyzing 2,935 variants in the thiopurine cytotoxicity-based assay, we identified 17 additional residues where variants altered NUDT15 activity without affecting protein stability. We identified structural elements key to NUDT15 stability and/or catalytical activity with single amino acid resolution. Functional effects for NUDT15 variants accurately predicted toxicity risk alleles in patients treated with thiopurines with far superior sensitivity and specificity compared to bioinformatic prediction algorithms. In conclusion, our massively parallel variant function assays identified 1,152 deleterious NUDT15 variants, providing a comprehensive reference of variant function and vastly improving the ability to implement pharmacogenetics-guided thiopurine treatment individualization.
|
|
| 3. |
- Beal, Jacob, et al.
(författare)
-
Robust estimation of bacterial cell count from optical density
- 2020
-
Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
-
Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
|
|
| 4. |
|
|
| 5. |
- Cantor-Graae, Elizabeth, et al.
(författare)
-
Long-term psychiatric consequences of exposure to trauma in Cambodia: A regional household survey.
- 2014
-
Ingår i: Social Science and Medicine. - : Elsevier BV. - 1873-5347 .- 0277-9536. ; 123, s. 133-140
-
Tidskriftsartikel (refereegranskat)abstract
- The long-term psychiatric consequences of exposure to war and/or mass conflict continue to be of great concern and particularly in Cambodia. The current cross-sectional study examined the relationship between history of trauma and current psychiatric and functional morbidity in 3200 randomly selected adults aged 18-60 in Cambodia. Structured interviews were conducted from November 2011 until May 2012 in two predominantly rural regions purposively selected for differing duration of exposure to the Khmer Rouge occupation. Information was also collected regarding ongoing daily stressors and intimate partner violence. Despite high prevalence rates of conflict/war-related trauma, current rates of psychiatric disorders (depression, post-traumatic stress disorder) were relatively low, suggesting that the effects of trauma and extreme hardship in civilian populations may be modified by contextual factors and/or the passage of time. Poor to fair physical health was, however, reported by nearly 60% of the sample. Daily stressors were more important for current morbidity levels than history of trauma, especially in the region with shorter Khmer Rouge occupation. The results suggest that a focus exclusively on past trauma may overlook the contribution of adverse daily life circumstances towards current levels of well-being in civilian populations affected by war and/or mass conflict.
|
|
| 6. |
- Jarl, Johan, et al.
(författare)
-
Trauma and Poor Mental Health in Relation to Economic Status: The Case of Cambodia 35 Years Later.
- 2015
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:8
-
Tidskriftsartikel (refereegranskat)abstract
- Cambodia is one of the poorest countries in south-east Asia and is still emerging from the events of the Khmer Rouge reign. It has been suggested that the atrocities experienced by the Cambodian population can explain why Cambodia continues to lag behind its neighbours in economic outcomes. The purpose of this study is to investigate whether there is an association between exposure to past trauma and/or current poor mental health and current economic status in Cambodia.
|
|
