| 1. |
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| 2. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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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.
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| 3. |
- Bertola, Laura D., et al.
(författare)
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A pragmatic approach for integrating molecular tools into biodiversity conservation
- 2024
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Ingår i: Conservation science and practice. - 2578-4854. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Molecular tools are increasingly applied for assessing and monitoring biodiversity and informing conservation action. While recent developments in genetic and genomic methods provide greater sensitivity in analysis and the capacity to address new questions, they are not equally available to all practitioners: There is considerable bias across institutions and countries in access to technologies, funding, and training. Consequently, in many cases, more accessible traditional genetic data (e.g., microsatellites) are still utilized for making conservation decisions. Conservation approaches need to be pragmatic by tackling clearly defined management questions and using the most appropriate methods available, while maximizing the use of limited resources. Here we present some key questions to consider when applying the molecular toolbox for accessible and actionable conservation management. Finally, we highlight a number of important steps to be addressed in a collaborative way, which can facilitate the broad integration of molecular data into conservation. Molecular tools are increasingly applied in conservation management; however, they are not equally available to all practitioners. We here provide key questions when establishing a conservation genetic study and highlight important steps which need to be addressed when these tools are globally applied.image
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| 4. |
- Deming, Yuetiva, et al.
(författare)
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Genome-wide association study identifies four novel loci associated with Alzheimer’s endophenotypes and disease modifiers
- 2017
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 133:5, s. 839-856
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Tidskriftsartikel (refereegranskat)abstract
- More than 20 genetic loci have been associated with risk for Alzheimer’s disease (AD), but reported genome-wide significant loci do not account for all the estimated heritability and provide little information about underlying biological mechanisms. Genetic studies using intermediate quantitative traits such as biomarkers, or endophenotypes, benefit from increased statistical power to identify variants that may not pass the stringent multiple test correction in case–control studies. Endophenotypes also contain additional information helpful for identifying variants and genes associated with other aspects of disease, such as rate of progression or onset, and provide context to interpret the results from genome-wide association studies (GWAS). We conducted GWAS of amyloid beta (Aβ42), tau, and phosphorylated tau (ptau181) levels in cerebrospinal fluid (CSF) from 3146 participants across nine studies to identify novel variants associated with AD. Five genome-wide significant loci (two novel) were associated with ptau181, including loci that have also been associated with AD risk or brain-related phenotypes. Two novel loci associated with Aβ42 near GLIS1 on 1p32.3 (β = −0.059, P = 2.08 × 10−8) and within SERPINB1 on 6p25 (β = −0.025, P = 1.72 × 10−8) were also associated with AD risk (GLIS1: OR = 1.105, P = 3.43 × 10−2), disease progression (GLIS1: β = 0.277, P = 1.92 × 10−2), and age at onset (SERPINB1: β = 0.043, P = 4.62 × 10−3). Bioinformatics indicate that the intronic SERPINB1 variant (rs316341) affects expression of SERPINB1 in various tissues, including the hippocampus, suggesting that SERPINB1 influences AD through an Aβ-associated mechanism. Analyses of known AD risk loci suggest CLU and FERMT2 may influence CSF Aβ42 (P = 0.001 and P = 0.009, respectively) and the INPP5D locus may affect ptau181 levels (P = 0.009); larger studies are necessary to verify these results. Together the findings from this study can be used to inform future AD studies.
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| 5. |
- Hoban, Sean, et al.
(författare)
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Genetic diversity goals and targets have improved, but remain insufficient for clear implementation of the post-2020 global biodiversity framework
- 2023
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Ingår i: Conservation Genetics. - : Springer Science and Business Media LLC. - 1566-0621 .- 1572-9737. ; 24:2, s. 181-191
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Tidskriftsartikel (refereegranskat)abstract
- Genetic diversity among and within populations of all species is necessary for people and nature to survive and thrive in a changing world. Over the past three years, commitments for conserving genetic diversity have become more ambitious and specific under the Convention on Biological Diversity’s (CBD) draft post-2020 global biodiversity framework (GBF). This Perspective article comments on how goals and targets of the GBF have evolved, the improvements that are still needed, lessons learned from this process, and connections between goals and targets and the actions and reporting that will be needed to maintain, protect, manage and monitor genetic diversity. It is possible and necessary that the GBF strives to maintain genetic diversity within and among populations of all species, to restore genetic connectivity, and to develop national genetic conservation strategies, and to report on these using proposed, feasible indicators.
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| 6. |
- Hoban, Sean, et al.
(författare)
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Genetic diversity targets and indicators in the CBD post-2020 Global Biodiversity Framework must be improved
- 2020
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Ingår i: Biological Conservation. - : Elsevier BV. - 0006-3207 .- 1873-2917. ; 248
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Tidskriftsartikel (refereegranskat)abstract
- The 196 parties to the Convention on Biological Diversity (CBD) will soon agree to a post-2020 global framework for conserving the three elements of biodiversity (genetic, species, and ecosystem diversity) while ensuring sustainable development and benefit sharing. As the most significant global conservation policy mechanism, the new CBD framework has far-reaching consequences- it will guide conservation actions and reporting for each member country until 2050. In previous CBD strategies, as well as other major conservation policy mechanisms, targets and indicators for genetic diversity (variation at the DNA level within species, which facilitates species adaptation and ecosystem function) were undeveloped and focused on species of agricultural relevance. We assert that, to meet global conservation goals, genetic diversity within all species, not just domesticated species and their wild relatives, must be conserved and monitored using appropriate metrics. Building on suggestions in a recent Letter in Science (Laikre et al., 2020) we expand argumentation for three new, pragmatic genetic indicators and modifications to two current indicators for maintaining genetic diversity and adaptive capacity of all species, and provide guidance on their practical use. The indicators are: 1) the number of populations with effective population size above versus below 500, 2) the proportion of populations maintained within species, 3) the number of species and populations in which genetic diversity is monitored using DNA-based methods. We also present and discuss Goals and Action Targets for post-2020 biodiversity conservation which are connected to these indicators and underlying data. These pragmatic indicators and goals have utility beyond the CBD; they should benefit conservation and monitoring of genetic diversity via national and global policy for decades to come.
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| 7. |
- Hoban, Sean, et al.
(författare)
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Global Commitments to Conserving and Monitoring Genetic Diversity Are Now Necessary and Feasible
- 2021
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Ingår i: BioScience. - : Oxford University Press (OUP). - 0006-3568 .- 1525-3244. ; 71:9, s. 964-976
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Tidskriftsartikel (refereegranskat)abstract
- Global conservation policy and action have largely neglected protecting and monitoring genetic diversity-one of the three main pillars of biodiversity. Genetic diversity (diversity within species) underlies species' adaptation and survival, ecosystem resilience, and societal innovation. The low priority given to genetic diversity has largely been due to knowledge gaps in key areas, including the importance of genetic diversity and the trends in genetic diversity change; the perceived high expense and low availability and the scattered nature of genetic data; and complicated concepts and information that are inaccessible to policymakers. However, numerous recent advances in knowledge, technology, databases, practice, and capacity have now set the stage for better integration of genetic diversity in policy instruments and conservation efforts. We review these developments and explore how they can support improved consideration of genetic diversity in global conservation policy commitments and enable countries to monitor, report on, and take action to maintain or restore genetic diversity.
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| 8. |
- Hoban, Sean, et al.
(författare)
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Too simple, too complex, or just right? Advantages, challenges, and guidance for indicators of genetic diversity
- 2024
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Ingår i: BioScience. - 0006-3568 .- 1525-3244.
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Tidskriftsartikel (refereegranskat)abstract
- Measuring genetic diversity of wild species using DNA-based data remains resource intensive and time consuming for nearly all species. However, genetic assessments are needed for global conservation commitments, including the Convention on Biological Diversity, and for governments and managers to evaluate conservation progress, as well as prioritizing species and populations to preserve and recover genetic diversity (e.g., via genetic rescue). Recently, indicators were developed for tracking and reporting genetic diversity status and trends for hundreds of species. The indicators quantify two simple proxies of within-population and among-population genetic diversity and adaptive potential: small effective population size (Ne < 500) and the loss of genetically distinct populations. The indicators must balance scientific credibility, practicality, and simplicity. In the present article, we summarize the advantages of these pragmatic indicators, address critiques by scientists for simplifying assumptions and by policymakers for complexity, and propose potential solutions and next steps. We aim to support practitioners putting indicators into policy, action, legislation, and reporting.
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| 9. |
- Im, Annie, et al.
(författare)
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Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide
- 2020
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Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 26:8, s. 1459-1468
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Tidskriftsartikel (refereegranskat)abstract
- Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P = .002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P < .001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus <29 years) was significantly associated with higher rates of grade 2 to 4 acute GVHD (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11 to 2.12; P = .01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR, 1.70; 95% CI, 1.11 to 2.62; P = .01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haplo-HCT. Our results indicate that in RIC haplo-HCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival.
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| 10. |
- Kershaw, Francine, et al.
(författare)
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The Coalition for Conservation Genetics : Working across organizations to build capacity and achieve change in policy and practice
- 2022
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Ingår i: Conservation Science and Practice. - : Wiley. - 2578-4854. ; 4:4
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Tidskriftsartikel (refereegranskat)abstract
- The Coalition for Conservation Genetics (CCG) brings together four eminent organizations with the shared goal of improving the integration of genetic information into conservation policy and practice. We provide a historical context of conservation genetics as a field and reflect on current barriers to conserving genetic diversity, highlighting the need for collaboration across traditional divides, international partnerships, and coordinated advocacy. We then introduce the CCG and illustrate through examples how a coalition approach can leverage complementary expertise and improve the organizational impact at multiple levels. The CCG has proven particularly successful at implementing large synthesis-type projects, training early-career scientists, and advising policy makers. Achievements to date highlight the potential for the CCG to make effective contributions to practical conservation policy and management that no one “parent” organization could achieve on its own. Finally, we reflect on the lessons learned through forming the CCG, and our vision for the future.
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| 11. |
- Koehbach, Johannes, et al.
(författare)
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Oxytocic plant cyclotides as templates for peptide G protein-coupled receptor ligand design
- 2013
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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. ; 110:52, s. 21183-21188
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Tidskriftsartikel (refereegranskat)abstract
- Cyclotides are plant peptides comprising a circular backbone and three conserved disulfide bonds that confer them with exceptional stability. They were originally discovered in Oldenlandia affinis based on their use in traditional African medicine to accelerate labor. Recently, cyclotides have been identified in numerous plant species of the coffee, violet, cucurbit, pea, potato, and grass families. Their unique structural topology, high stability, and tolerance to sequence variation make them promising templates for the development of peptide-based pharmaceuticals. However, the mechanisms underlying their biological activities remain largely unknown; specifically, a receptor for a native cyclotide has not been reported hitherto. Using bioactivity-guided fractionation of an herbal peptide extract known to indigenous healers as "kalata-kalata," the cyclotide kalata B7 was found to induce strong contractility on human uterine smooth muscle cells. Radioligand displacement and second messenger-based reporter assays confirmed the oxytocin and vasopressin V-1a receptors, members of the G protein-coupled receptor family, as molecular targets for this cyclotide. Furthermore, we show that cyclotides can serve as templates for the design of selective G protein-coupled receptor ligands by generating an oxytocin-like peptide with nanomolar affinity. This nonapeptide elicited dose-dependent contractions on human myometrium. These observations provide a proof of concept for the development of cyclotide-based peptide ligands.
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| 12. |
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