| 1. |
- 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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| 2. |
- Aponte-Santamaria, C., et al.
(författare)
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Temperature dependence of protein-water interactions in a gated yeast aquaporin
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Regulation of aquaporins is a key process of living organisms to counteract sudden osmotic changes. Aqy1, which is a water transporting aquaporin of the yeast Pichia pastoris, is suggested to be gated by chemo-mechanical stimuli as a protective regulatory-response against rapid freezing. Here, we tested the influence of temperature by determining the X-ray structure of Aqy1 at room temperature (RT) at 1.3 angstrom resolution, and by exploring the structural dynamics of Aqy1 during freezing through molecular dynamics simulations. At ambient temperature and in a lipid bilayer, Aqy1 adopts a closed conformation that is globally better described by the RT than by the low-temperature (LT) crystal structure. Locally, for the blocking-residue Tyr31 and the water molecules inside the pore, both LT and RT data sets are consistent with the positions observed in the simulations at room-temperature. Moreover, as the temperature was lowered, Tyr31 adopted a conformation that more effectively blocked the channel, and its motion was accompanied by a temperature-driven rearrangement of the water molecules inside the channel. We therefore speculate that temperature drives Aqy1 from a loosely-to a tightly-blocked state. This analysis provides high-resolution structural evidence of the influence of temperature on membrane-transport channels.
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| 3. |
- Brändén, Magnus, 1971, et al.
(författare)
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Refractive-Index-Based Screening of Membrane-Protein-Mediated Transfer across Biological Membranes
- 2010
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Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 99:1, s. 124-133
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Tidskriftsartikel (refereegranskat)abstract
- Numerous membrane-transport proteins are major drug targets, and therefore a key ingredient in pharmaceutical development is the availability of reliable, efficient tools for membrane transport characterization and inhibition. Here, we present the use of evanescent-wave sensing for screening of membrane-protein-mediated transport across lipid bilayer membranes. This method is based on a direct recording of the temporal variations in the refractive index that occur upon a transfer-dependent change in the solute concentration inside liposomes associated to a surface plasmon resonance (SPR) active sensor surface. The applicability of the method is demonstrated by a functional study of the aquaglyceroporin PfAQP from the malaria parasite Plasmodium falciparum. Assays of the temperature dependence of facilitated diffusion of sugar alcohols on a single set of PfAQP-reconstituted liposomes reveal that the activation energies for facilitated diffusion of xylitol and sorbitol are the same as that previously measured for glycerol transport in the aquaglyceroporin of Escherichia coli (5 kcal/mole). These findings indicate that the aquaglyceroporin selectivity filter does not discriminate sugar alcohols based on their length, and that the extra energy cost of dehydration of larger sugar alcohols, upon entering the pore, is compensated for by additional hydrogen-bond interactions within the aquaglyceroporin pore.
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| 4. |
- Di, Li, et al.
(författare)
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Evidence-based approach to assess passive diffusion and carrier-mediated drug transport
- 2012
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Ingår i: Drug Discovery Today. - : Elsevier BV. - 1359-6446 .- 1878-5832. ; 17:15-16, s. 905-912
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Forskningsöversikt (refereegranskat)abstract
- Evidence supporting the action of passive diffusion and carrier-mediated (CM) transport in drug bioavailability and disposition is discussed to refute the recently proposed theory that drug transport is CM-only and that new transporters will be discovered that possess transport characteristics ascribed to passive diffusion. Misconceptions and faulty speculations are addressed to provide reliable guidance on choosing appropriate tools for drug design and optimization.
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| 5. |
- Fischer, Gerhard, 1978, et al.
(författare)
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Crystal structure of a yeast aquaporin at 1.15 angstrom reveals a novel gating mechanism.
- 2009
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Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1545-7885 .- 1544-9173. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- Aquaporins are transmembrane proteins that facilitate the flow of water through cellular membranes. An unusual characteristic of yeast aquaporins is that they frequently contain an extended N terminus of unknown function. Here we present the X-ray structure of the yeast aquaporin Aqy1 from Pichia pastoris at 1.15 A resolution. Our crystal structure reveals that the water channel is closed by the N terminus, which arranges as a tightly wound helical bundle, with Tyr31 forming H-bond interactions to a water molecule within the pore and thereby occluding the channel entrance. Nevertheless, functional assays show that Aqy1 has appreciable water transport activity that aids survival during rapid freezing of P. pastoris. These findings establish that Aqy1 is a gated water channel. Mutational studies in combination with molecular dynamics simulations imply that gating may be regulated by a combination of phosphorylation and mechanosensitivity.
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| 6. |
- Fischer, Gerhard, et al.
(författare)
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Rethinking and reinventing learning, education and collaboration in the digital age : from creating technologies to transforming cultures
- 2020
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Ingår i: The international journal of information and learning technology. - : Emerald Group Publishing Limited. - 2056-4880 .- 2056-4899. ; 37:5, s. 241-252
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The digitalization of society results in challenges and opportunities for learning and education. This paper describes exemplary transformations from current to future practices. It illustrates multi-dimensional aspects of learning which complement and transcend current frameworks of learning focused on schools. While digital technologies are necessary for these transformations, they are not sufficient. The paper briefly illustrates the applicability of the conceptual framework to the COVID-19 pandemic. It concludes that design opportunities and design trade-offs in relation to digital technologies and learning should be explored by envisioning the cultural transformation that are desirable for making learning a part of life.Design/methodology/approach: This paper is based on the work conducted at the symposium "Rethinking and Reinventing Learning, Education, and Collaboration in the Digital Age-From Creating Technologies to Transforming Cultures" that took place in Engeltofta outside of Gavle, Sweden in September 2019. The symposium invited scholars in collaborative analysis of design opportunities and design trade-offs in relation to digital technologies and learning and explored design strategies for systematically and proactively increasing digital technology's contributions to learning and collaborating. The paper first provides a condensed introduction of a conceptual framework summarizing current practices, their problems and promising alternatives. Multi-dimensional aspects of learning and lifelong learning will be briefly described as promising future alternatives to school learning. Examples of transformative practices are supporting the major argument of the paper that creating new technologies is an important prerequisite to address the fundamental challenge of transforming cultures. The unanticipated but fundamental event of the occurrence of COVID-19 will be briefly described to provide further evidence for the need and the applicability of our conceptual framework for rethinking and reinventing learning, education and collaboration in the digital age.Findings: The paper provides a condensed introduction of a conceptual framework summarizing current practices, their problems and promising alternatives. The framework includes multi-dimensional aspects of learning and lifelong learning as a promising future alternative to a focus on school learning.Originality/value: This paper describes exemplary transformations from current to future practices. It illustrates multi-dimensional aspects of learning which complement and transcend current frameworks of learning focused on schools.
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| 7. |
- Fischer, Gerhard, 1978
(författare)
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Structure and Function of Aqua(glycero)porins - A Path to Drug Design
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Membrane proteins are a major class of the drug targets. Rational design of drugs requires knowledge about the structure and function of these proteins. Working with membrane proteins, however, is experimentally challenging as the required technology is still emerging. Water being the medium of life, Nature has evolved specialized water channels called aquaporins. These transporters are found in all kingdoms of life – from simple microorganisms to humans – and function to maintain water homeostasis. These water channels are surprisingly similar in structure and are divided into two major groups: While orthodox aquaporins transport water only, the closely related aquaglyceroporins also transport small solutes like glycerol or other sugar alcohols. Aquaporins have been suggested to be involved in a wide variety of human disorders, but also as a means to combat malicious parasites. During the course of this work, we discovered the only aquaporin from the yeast Pichia pastoris. We determined its atomic structure using X-ray crystallography to 0.90 Å resolution, the highest resolution for any membrane protein to date. Surprisingly, this structure showed the water pore being closed by its elongated N-terminus and provided in detail information on the water transport mechanism through this pore. Further functional characterization by a combination of size-based water conduction assays and temperature-dependent crystallography revealed that the channel can be opened. We suggested a gating mechanism via phosphorylation and mechanosensing, which was found to be beneficial to the survival of the organism. Medically, protein structures like these can also be used for rational drug design. For aqua(glycero)porins, however, the discovery of inhibitors is hampered by the lack of a medium- to high-throughput assay to test potential channel blockers. Using novel technology based on surface plasmon resonance (Biacore™), we established a fully automated drug screening assay with the capability to test up to 50 compounds/day. Application of this method in combination with virtual screening yielded a drug lead with an IC50-value of 1-10 μM against the aquaglyceroporin from the malaria parasite Plasmodium falciparum.
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| 8. |
- Fischer, Gerhard, et al.
(författare)
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The challenge for the digital age : making learning a part of life
- 2023
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Ingår i: The international journal of information and learning technology. - : Emerald Group Publishing Limited. - 2056-4880 .- 2056-4899. ; 40:1, s. 1-16
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The main argument behind this paper is learning in the digital age should not be restricted to creating digital infrastructures for supporting current forms of learning nor taking schools in their current form as God-given, natural entities, but changing current forms of education by developing new frameworks and socio-technical environments for making learning an integral part of life. The authors provide a framework for this argumentation as well as a call-to-action for research on the co-evolution of learning, media, and learning organizations. Design/methodology/approach: This paper theoretically and argumentatively explores the core assumption that the digitalization of society results in challenges and opportunities for learning and education based on fundamental transformations (Collins and Halverson, 2009; Fischer et al., 2020). Findings: The digital age greatly enhances the opportunities and supports the necessity for “making learning a part of life”. But while the growth of technology is certain, the inevitability of any particular future is not. The impact of schooling goes beyond that new information about computers, the Internet, and social media are integrated into the schools of today. The transformation of schools needs to be informed by an understanding of the impact of mindset formation that will determine people’s approach to learning for the rest of their lives. The authors’ framework is focused on moving “beyond gift-wrapping” by not only fixing and existing systems but to change them and not only reforming but transforming them. Originality/value: It is the authors’ hope that this article will be of interest to many stakeholders (including learners, teachers, curriculum designers, technology experts, parents, and politicians) and provide a foundation for an ongoing debate and informed actions for “Making Learning a Part of Life” in the digital age. © 2022, Gerhard Fischer, Johan Lundin and Ola J. Lindberg.
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| 9. |
- Fischer, Vinicius Jobim, et al.
(författare)
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A randomized controlled trial of an Internet-based emotion regulation intervention for sexual health : study protocol
- 2021
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Ingår i: Trials. - : BMC. - 1745-6215. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Emotion regulation difficulties have been associated with mental disorders and sexual dysfunctions. Traditional face-to-face transdiagnostic emotion regulation interventions have shown positive results for emotional and personality disorders. Only recently have the effects of these interventions on sexual health started to be investigated. Internet-delivered psychological interventions have several advantages over face-to-face interventions, such as cost-effectiveness, accessibility, and suitability for people who experience shame because of their stigmatized problematic behaviors and those who avoid seeking help. The aims of the SHER 2-TREpS (Portuguese acronym for Emotion Regulation training for sexual health) project are as follows: (a) determine the efficacy of an Internet-based emotion regulation intervention for sexual health and sexual satisfaction and (b) explore the effects of the intervention on (1) emotion regulation skills, (2) mental health, and (3) sexual self-perception. Methods and analysis The study will use a randomized controlled trial design. Eligible participants will be randomly allocated to one of two groups: intervention (Internet-based emotion regulation training) or waitlist control. Assessments will take place before the start of the trial, at the end of the trial, and at 6-month follow up, after which participants assigned to the waitlist control condition will receive the same intervention. Primary outcomes include sexual function and satisfaction and secondary outcomes self-report measures of depression, anxiety, difficulties in emotion regulation, and sexual self-perception. This intervention study is financed by the Luxembourg National Research Fund (FNS). Ethics and dissemination Ethics approval was obtained from the Ethics Review Panel of the University of Luxembourg. Findings will be disseminated via peer-reviewed publications and conference presentations.
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| 10. |
- Fischer, Vinicius Jobim, et al.
(författare)
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The Relationship Between Emotion Regulation and Sexual Function and Satisfaction: A Scoping Review
- 2022
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Ingår i: Sexual Medicine Reviews. - : Elsevier. - 2050-0521. ; 10:2, s. 195-208
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Forskningsöversikt (refereegranskat)abstract
- Introduction: Sexual problems are characterized by difficulties in the ability to respond sexually or to obtain sexual pleasure. Their etiology is assumed to be multifactorial, demanding a biopsychosocial treatment approach. Positive sexual experiences involve the dynamic interplay between cognitive, emotional, and motivational factors. Difficulties in emotion identification or impairment in emotion regulation may thus play a pivotal role in the development and maintenance of sexual problems.Objectives: To conduct a scoping review of the literature on the effects of emotion regulation on sexual function and satisfaction.Methods: We conducted a scoping review using Cinahl, Lilacs, Scielo, Scopus, PsycInfo and Pubmed electronic databases using search terms related to emotion regulation and sexual function and satisfaction.Results: 27 articles met the inclusion criteria and were further analyzed. Overall, emotion regulation difficulties were associated with poorer sexual health outcomes, difficulties in the sexual response cycle and overall lower sexual satisfaction. Laboratory studies and intervention trials found positive effects of promoting emotion regulation change on sexual function and satisfaction.Conclusions: Despite the methodological diversity of studies, it can be concluded from this review that difficulties in emotion regulation are related to sexual difficulties and sexual dissatisfaction. Future research should consider emotion regulation-focused interventions to mitigate sexual health problems.
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