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- Buchanan, E. M., et al.
(författare)
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The Psychological Science Accelerator's COVID-19 rapid-response dataset
- 2023
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data.
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| 6. |
- Pantazis, A., et al.
(författare)
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Tracking the motion of the KV1.2 voltage sensor reveals the molecular perturbations caused by a de novo mutation in a case of epilepsy
- 2020
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Ingår i: Journal of Physiology. - : Blackwell Publishing Ltd. - 0022-3751 .- 1469-7793.
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Tidskriftsartikel (refereegranskat)abstract
- Key points: KV1.2 channels, encoded by the KCNA2 gene, regulate neuronal excitability by conducting K+ upon depolarization. A new KCNA2 missense variant was discovered in a patient with epilepsy, causing amino acid substitution F302L at helix S4, in the KV1.2 voltage-sensing domain. Immunocytochemistry and flow cytometry showed that F302L does not impair KCNA2 subunit surface trafficking. Molecular dynamics simulations indicated that F302L alters the exposure of S4 residues to membrane lipids. Voltage clamp fluorometry revealed that the voltage-sensing domain of KV1.2-F302L channels is more sensitive to depolarization. Accordingly, KV1.2-F302L channels opened faster and at more negative potentials; however, they also exhibited enhanced inactivation: that is, F302L causes both gain- and loss-of-function effects. Coexpression of KCNA2-WT and -F302L did not fully rescue these effects. The proband's symptoms are more characteristic of patients with loss of KCNA2 function. Enhanced KV1.2 inactivation could lead to increased synaptic release in excitatory neurons, steering neuronal circuits towards epilepsy. Abstract: An exome-based diagnostic panel in an infant with epilepsy revealed a previously unreported de novo missense variant in KCNA2, which encodes voltage-gated K+ channel KV1.2. This variant causes substitution F302L, in helix S4 of the KV1.2 voltage-sensing domain (VSD). F302L does not affect KCNA2 subunit membrane trafficking. However, it does alter channel functional properties, accelerating channel opening at more hyperpolarized membrane potentials, indicating gain of function. F302L also caused loss of KV1.2 function via accelerated inactivation onset, decelerated recovery and shifted inactivation voltage dependence to more negative potentials. These effects, which are not fully rescued by coexpression of wild-type and mutant KCNA2 subunits, probably result from the enhancement of VSD function, as demonstrated by optically tracking VSD depolarization-evoked conformational rearrangements. In turn, molecular dynamics simulations suggest altered VSD exposure to membrane lipids. Compared to other encephalopathy patients with KCNA2 mutations, the proband exhibits mild neurological impairment, more characteristic of patients with KCNA2 loss of function. Based on this information, we propose a mechanism of epileptogenesis based on enhanced KV1.2 inactivation leading to increased synaptic release preferentially in excitatory neurons, and hence the perturbation of the excitatory/inhibitory balance of neuronal circuits.
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| 7. |
- Neiburga, KD, et al.
(författare)
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Vascular Tissue Specific miRNA Profiles Reveal Novel Correlations with Risk Factors in Coronary Artery Disease
- 2021
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Ingår i: Biomolecules. - : MDPI AG. - 2218-273X. ; 11:11
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Tidskriftsartikel (refereegranskat)abstract
- Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Non-coding RNAs have already been linked to CVD development and progression. While microRNAs (miRs) have been well studied in blood samples, there is little data on tissue-specific miRs in cardiovascular relevant tissues and their relation to cardiovascular risk factors. Tissue-specific miRs derived from Arteria mammaria interna (IMA) from 192 coronary artery disease (CAD) patients undergoing coronary artery bypass grafting (CABG) were analyzed. The aims of the study were 1) to establish a reference atlas which can be utilized for identification of novel diagnostic biomarkers and potential therapeutic targets, and 2) to relate these miRs to cardiovascular risk factors. Overall, 393 individual miRs showed sufficient expression levels and passed quality control for further analysis. We identified 17 miRs–miR-10b-3p, miR-10-5p, miR-17-3p, miR-21-5p, miR-151a-5p, miR-181a-5p, miR-185-5p, miR-194-5p, miR-199a-3p, miR-199b-3p, miR-212-3p, miR-363-3p, miR-548d-5p, miR-744-5p, miR-3117-3p, miR-5683 and miR-5701–significantly correlated with cardiovascular risk factors (correlation coefficient >0.2 in both directions, p-value (p < 0.006, false discovery rate (FDR) <0.05). Of particular interest, miR-5701 was positively correlated with hypertension, hypercholesterolemia, and diabetes. In addition, we found that miR-629-5p and miR-98-5p were significantly correlated with acute myocardial infarction. We provide a first atlas of miR profiles in IMA samples from CAD patients. In perspective, these miRs might play an important role in improved risk assessment, mechanistic disease understanding and local therapy of CAD.
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- Axelsson, Anton, 1991, et al.
(författare)
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Asymmetric Synthesis of Dihydropyranones with Three Contiguous Stereocenters by an NHC-Catalyzed Kinetic Resolution
- 2021
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Ingår i: European Journal of Organic Chemistry. - : Wiley. - 1434-193X .- 1099-0690. ; 2021:25, s. 3657-3661
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Tidskriftsartikel (refereegranskat)abstract
- An oxidative NHC-catalyzed kinetic resolution (KR) of racemic mixtures is presented. The developed reaction furnishes tricyclic dihydropyranones with three contiguous stereocenters in excellent dia- and enantioselectivity, with good-to-moderate yields. Mechanistic studies indicate that the rate-determining step of the reaction is the formation of the Breslow intermediate, while the selectivity determining step occurs later in the mechanism. The presented methodology enables rapid synthesis of complex structures in a single step.
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