| 1. |
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| 2. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 4. |
- Amare, Azmeraw, et al.
(författare)
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Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder.
- 2023
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Ingår i: Research square. - : Research Square Platform LLC.
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2,367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������.
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| 5. |
- Amare, Azmeraw T, et al.
(författare)
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Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.
- 2023
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Ingår i: Molecular psychiatry. - 1476-5578. ; 28, s. 5251-5261
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental healthdisorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P=9.8×10-12, R2=1.9%) and continuous (P=6.4×10-9, R2=2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P=3.9×10-4, R2=0.9%), but not for the continuous outcome (P=0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
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| 6. |
- Baiao, Guilherme Costa, et al.
(författare)
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Differential gene expression in semispecies and hybrids of Drosophila paulistorum
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Gene expression divergence is correlated with and can be either a cause or a consequence of species divergence. Studying gene expression differences between closely related species, and their hybrid offspring, can thus give us clues about genes and mechanisms associated with reproductive isolation (RI) between them and allow us to better understand early stages of speciation. In this study, we use RNA-Seq to investigate gene expression divergence between the Amazonian, Centro-American and Orinocan semispecies of Drosophila paulistorum, a species cluster in statu nascendi, and between inter-semispecies hybrids and their parents. We uncover a large number of genes with varying expression between semispecies, with the highest numbers in male abdomens. The differentially expressed genes are associated with a range of biological functions, but especially with broad, regulatory functions, that are governed by transcription, translation, post-translational modifications and induced by signal transduction. We found that the expression pattern of hybrids was much more similar to the maternal line and that very few genes have a different expression than both of their parents. When comparing the differentially expressed genes in semispecies and hybrids to gene affected by Wolbachia in D. paulistorum, we see a small overlap. However, especially in hybrids, some of the overlapping genes appear to be highly relevant. Our study provides insights about expression differences associated with RI in D. paulistorum, and the impact of Wolbachia on the divergence of semispecies and hybrid sterility.
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| 7. |
- Baiao, Guilherme Costa, 1984-, et al.
(författare)
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Multiple introgressions shape mitochondrial evolutionary history in Drosophila paulistorum and the Drosophila willistoni group
- 2023
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Ingår i: Molecular Phylogenetics and Evolution. - : Elsevier. - 1055-7903 .- 1095-9513. ; 180
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Tidskriftsartikel (refereegranskat)abstract
- Hybridization and the consequent introgression of genomic elements is an important source of genetic diversity for biological lineages. This is particularly evident in young clades in which hybrid incompatibilities are still incomplete and mixing between species is more likely to occur. Drosophila paulistorum, a representative of the Neotropical Drosophila willistoni subgroup, is a classic model of incipient speciation. The species is divided into six semispecies that show varying degrees of pre-and post-mating incompatibility with each other. In the present study, we investigate the mitochondrial evolutionary history of D. paulistorum and the willistoni subgroup. For that, we perform phylogenetic and comparative analyses of the complete mitochondrial genomes and draft nuclear assemblies of 25 Drosophila lines of the willistoni and saltans species groups. Our results show that the mitochondria of D. paulistorum are polyphyletic and form two non-sister clades that we name alpha and beta. Identi-fication and analyses of nuclear mitochondrial insertions further reveal that the willistoni subgroup has an alpha-like mitochondrial ancestor and strongly suggest that both the alpha and beta mitochondria of D. paulistorum were acquired through introgression from unknown fly lineages of the willistoni subgroup. We also uncover multiple mito-chondrial introgressions across D. paulistorum semispecies and generate novel insight into the evolution of the species.
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| 8. |
- Baiao, Guilherme Costa, et al.
(författare)
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Persistence of high-level heteroplasmy through biparental transmission of a selfish mitochondrion in Drosophila paulistorum
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Heteroplasmy, or the coexistence of multiple mitotypes in an individual, has during recent years been shown to be more common in animals than previously anticipated. However, cases of stable, high-titer heteroplasmy are still relatively rare, as are systems with consistent paternal mitochondrial inheritance. In this study, we sequenced and assembled the full mitochondrial genomes of 23 Neotropical Drosophila lines belonging to six species of the willistoni group and three of the saltans group and discovered that 40% the 13 sequenced Drosophila paulistorum lines, are persistently heteroplasmic. We further showed that the mitochondria of D. paulistorum are polyphyletic, forming two clades, a and b, and that mitochondria of the a2 clade are exclusively found in heteroplasmic flies. Genomic analysis indicates that a2 is a functional mitochondrion, with no signs of loss of function mutations. Even so, our results demonstrate that a2 displays unusual features, including lack of titer response to energetic demands, higher titer in males than females, and consistent biparental transmission due to rapid replication during early embryo development. Together these features indicate that a2 might be a selfish mitochondrion that persists due to efficient biparental transmission.Using the assembled genomes, we reconstructed the evolutionary history of mitochondria in the willistoni subgroup and identified signs of multiple mitochondrial losses, gains and introgressions. The data indicated an a-like mitochondrial ancestor in the willistoni subgroup, with the b mitochondrion likely being acquired through introgression from an unidentified donor. We hypothesize that the selfish characteristics of a2 might have emerged as a response to competition for inheritance with the introgressed b
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| 9. |
- Baiao, Guilherme Costa, et al.
(författare)
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The effect of Wolbachia on gene expression in Drosophila paulistorum and its implications for symbiont-induced host speciation
- 2019
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 20
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Neotropical fruit fly Drosophila paulistorum (Diptera: Drosophilidae) is a species complex in statu nascendi comprising six reproductively isolated semispecies, each harboring mutualistic Wolbachia strains. Although wild type flies of each semispecies are isolated from the others by both pre- and postmating incompatibilities, mating between semispecies and successful offspring development can be achieved once flies are treated with antibiotics to reduce Wolbachia titer. Here we use RNA-seq to study the impact of Wolbachia on D. paulistorum and investigate the hypothesis that the symbiont may play a role in host speciation. For that goal, we analyze samples of heads and abdomens of both sexes of the Amazonian, Centro American and Orinocan semispecies of D. paulistorum.Results: We identify between 175 and 1192 differentially expressed genes associated with a variety of biological processes that respond either globally or according to tissue, sex or condition in the three semispecies. Some of the functions associated with differentially expressed genes are known to be affected by Wolbachia in other species, such as metabolism and immunity, whereas others represent putative novel phenotypes involving muscular functions, pheromone signaling, and visual perception.Conclusions: Our results show that Wolbachia affect a large number of biological functions in D. paulistorum, particularly when present in high titer. We suggest that the significant metabolic impact of the infection on the host may cause several of the other putative and observed phenotypes. We also speculate that the observed differential expression of genes associated with chemical communication and reproduction may be associated with the emergence of pre- and postmating barriers between semispecies, which supports a role for Wolbachia in the speciation of D. paulistorum.
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| 10. |
- Fazey, Ioan, et al.
(författare)
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Transforming knowledge systems for life on Earth : Visions of future systems and how to get there
- 2020
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Ingår i: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 70
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Tidskriftsartikel (refereegranskat)abstract
- Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.
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