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| 2. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 3. |
- Schweinsberg, Martin, et al.
(författare)
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Same data, different conclusions : Radical dispersion in empirical results when independent analysts operationalize and test the same hypothesis
- 2021
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Ingår i: Organizational Behavior and Human Decision Processes. - : Elsevier BV. - 0749-5978 .- 1095-9920. ; 165, s. 228-249
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Tidskriftsartikel (refereegranskat)abstract
- In this crowdsourced initiative, independent analysts used the same dataset to test two hypotheses regarding the effects of scientists' gender and professional status on verbosity during group meetings. Not only the analytic approach but also the operationalizations of key variables were left unconstrained and up to individual analysts. For instance, analysts could choose to operationalize status as job title, institutional ranking, citation counts, or some combination. To maximize transparency regarding the process by which analytic choices are made, the analysts used a platform we developed called DataExplained to justify both preferred and rejected analytic paths in real time. Analyses lacking sufficient detail, reproducible code, or with statistical errors were excluded, resulting in 29 analyses in the final sample. Researchers reported radically different analyses and dispersed empirical outcomes, in a number of cases obtaining significant effects in opposite directions for the same research question. A Boba multiverse analysis demonstrates that decisions about how to operationalize variables explain variability in outcomes above and beyond statistical choices (e.g., covariates). Subjective researcher decisions play a critical role in driving the reported empirical results, underscoring the need for open data, systematic robustness checks, and transparency regarding both analytic paths taken and not taken. Implications for orga-nizations and leaders, whose decision making relies in part on scientific findings, consulting reports, and internal analyses by data scientists, are discussed.
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| 4. |
- Keeler, Bonnie L., et al.
(författare)
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Social-ecological and technological factors moderate the value of urban nature
- 2019
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Ingår i: Nature Sustainability. - : Springer Science and Business Media LLC. - 2398-9629. ; 2:1, s. 29-38
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Forskningsöversikt (refereegranskat)abstract
- Urban nature has the potential to improve air and water quality, mitigate flooding, enhance physical and mental health, and promote social and cultural well-being. However, the value of urban ecosystem services remains highly uncertain, especially across the diverse social, ecological and technological contexts represented in cities around the world. We review and synthesize research on the contextual factors that moderate the value and equitable distribution of ten of the most commonly cited urban ecosystem services. Our work helps to identify strategies to more efficiently, effectively and equitably implement nature-based solutions.
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- MacDonald, Justin A, et al.
(författare)
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A Small Molecule Pyrazolo[3,4-d]pyrimidinone Inhibitor of Zipper-Interacting Protein Kinase Suppresses Calcium Sensitization of Vascular Smooth Muscle.
- 2016
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Ingår i: Molecular Pharmacology. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 1521-0111 .- 0026-895X. ; 89:1, s. 105-117
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Tidskriftsartikel (refereegranskat)abstract
- A novel inhibitor of zipper-interacting protein kinase (ZIPK) was utilized to examine the involvement of ZIPK in the regulation of smooth muscle contraction. Pre-treatment of de-endothelialized rat caudal arterial smooth muscle strips with the pyrazolo[3,4-d]pyrimidinone inhibitor HS38 decreased the velocity of contraction (time to reach half-maximal force) induced by the phosphatase inhibitor calyculin A in the presence of Ca2+ without affecting maximal force development. This effect was reversed following washout of HS38 and correlated with a reduction in the rate of phosphorylation of LC20 (myosin 20-kDa regulatory light chains) but not of CPI-17 (protein kinase C-potentiated inhibitory protein for myosin phosphatase of 17 kDa), Par-4 (prostate apoptosis response-4) or MYPT1 (myosin phosphatase targeting subunit 1), all of which have been implicated in the regulation of vascular contractility. A structural analog of HS38, with inhibitory activity towards PIM3 kinase but not ZIPK, had no effect on calyculin A-induced contraction or protein phosphorylations. We conclude that a pool of constitutively-active ZIPK is involved in regulation of vascular smooth muscle contraction through direct phosphorylation of LC20 upon inhibition of myosin light chain phosphatase activity. HS38 also significantly attenuated both phasic and tonic contractile responses elicited by phenylephrine, angiotensin II, endothelin-1, U46619 and K+-induced membrane depolarization in the presence of Ca2+, which correlated with inhibition of phosphorylation of LC20, MYPT1 and CPI-17. These effects of HS38 suggest that ZIPK also lies downstream of G protein-coupled receptors that signal through both Gα12/13 and Gαq/11.
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| 6. |
- Kitchen, Philip, et al.
(författare)
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Targeting Aquaporin-4 Subcellular Localization to Treat Central Nervous System Edema
- 2020
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Ingår i: Cell. - : Elsevier BV. - 0092-8674. ; 181:4, s. 19-799
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Tidskriftsartikel (refereegranskat)abstract
- Swelling of the brain or spinal cord (CNS edema) affects millions of people every year. All potential pharmacological interventions have failed in clinical trials, meaning that symptom management is the only treatment option. The water channel protein aquaporin-4 (AQP4) is expressed in astrocytes and mediates water flux across the blood-brain and blood-spinal cord barriers. Here we show that AQP4 cell-surface abundance increases in response to hypoxia-induced cell swelling in a calmodulin-dependent manner. Calmodulin directly binds the AQP4 carboxyl terminus, causing a specific conformational change and driving AQP4 cell-surface localization. Inhibition of calmodulin in a rat spinal cord injury model with the licensed drug trifluoperazine inhibited AQP4 localization to the blood-spinal cord barrier, ablated CNS edema, and led to accelerated functional recovery compared with untreated animals. We propose that targeting the mechanism of calmodulin-mediated cell-surface localization of AQP4 is a viable strategy for development of CNS edema therapies.
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