263134 research outputs found
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WeMu: Effective and Scalable Emulation of Microarchitectural Weird Machines
No full textsponsorship: Research Foundation - Flanders (FWO)|12B2A24Nstatus: Accepte
'It is always putting things into words, but now it was about feeling, truly feeling': <i>Affect Houses</i> as a novel method to attend to of affect
No full textsponsorship: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was funded by the FWO (https://www.fwo.be/nl/). Grant number: 12A8Q25N. (FWO|12A8Q25N)status: Published onlin
Machine learning on the edge for sustainable IoT networks: A systematic literature review
No full textsponsorship: The present work has received funding from the European Union's Horizon 2020 Marie Sk & lstrok;odowska Curie Innovative Training Network Greenedge (GA. No. 953775) . (European Union|953775)status: Accepte
Do commodity markets support the circular economy? Evidence from agri-food companies
No full textsponsorship: Funding by Internal Funds KU Leuven (C2 project 3H240469) is gratefully acknowledged. (Internal Funds KU Leuven|3H240469)status: Published onlin
Behavioral constructs and neural correlates of descriptive and responsive speech in post-stroke aphasia
No full textDiscourse refers to language that extends beyond a single clause and is used to express ideas, feelings or to interact with others. Persons with post-stroke aphasia often encounter difficulties in discourse, which can severely impede everyday communication. In recent years, discourse has received more attention in both research and clinical practice due to its high ecological validity. However, little is known about the underlying behavioral constructs and neural correlates of discourse in post-stroke aphasia. In the current study, discourse was assessed in 49 persons with chronic aphasia following left-hemispheric (n = 39) or bilateral (n = 10) stroke using picture description from the CAT (descriptive speech) and verbal responses to everyday scenarios from the ANELT (responsive speech). Factor analysis and voxel-wise lesion symptom mapping were performed to investigate the underlying behavioral and neural constructs. Factor analysis revealed four latent constructs that explained 64% of the total variance in the discourse variables: grammatical, phonological, lexical-semantic and macrostructural. Fluency variables were spread across these four different factors. For example, digression was associated with word repetitions and filled pauses, while grammatical deficits were associated with speech rate and long pauses. After correction for multiple comparisons, only the lexical-semantic factor was significantly associated with a left cluster covering lesions in the inferior parietal, superior and middle temporal and lateral occipital regions. In conclusion, this study shows that discourse analysis can reveal both clustered and distributed dimensions and further establishes the role of the left inferior parietal and superior and middle temporal lobe in lexical-semantic abilities.sponsorship: This work was supported by the Research Foundation Flanders (Fonds Wetenschappelijk Onderzoek) , Award ID 1SH1Q24N to Mara Barberis and Award ID G0D8520N to Maaike Vandermosten. (Research Foundation Flanders (Fonds Wetenschappelijk Onderzoek)|1SH1Q24N, Research Foundation Flanders (Fonds Wetenschappelijk Onderzoek)|G0D8520N)status: Accepte
A duo of redox-sensitive pore-loop cysteines controls the activity of the neural ion channel TRPM3.
No full textTransient Receptor Potential Melastatin 3 (TRPM3) is a non-selective, Ca2+-permeable ion channel that plays a pivotal role in peripheral thermosensation and nociception. Moreover, gain-of-function variants in TRPM3 underlie a spectrum of neurodevelopmental and epileptic disorders in humans, indicating an important role of TRPM3 in the central nervous system. Oxidative stress contributes to various neurological disorders of both the central and peripheral nervous system, but it is unknown whether TRPM3 activity is altered by the cellular redox state. Here, we report a direct, bidirectional modification of TRPM3 channel activity by oxidizing and reducing agents. Our data demonstrate a profound effect of the redox state on the channel properties of TRPM3, including a robust shift in the response profile to pharmacology and temperature sensitivity. In addition, we identified two cysteine residues in the extracellular pore loop of TRPM3 that underlie the redox-control of the channel, due to the reversible formation of intra-subunit cysteine bridges. Taken together, these observations raise the hypothesis that TRPM3 could be modulated through an alternative mechanism, potentially affecting pathways involved in pain and neurological function.sponsorship: KU Leuven (Katholieke Universiteit Leuven)|C14/24/152, Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)|G.084515Nstatus: Published onlin
Continuous glucose monitoring metrics and pregnancy outcomes in type 1 diabetes: a secondary analysis of the CRISTAL trial
No full textstatus: Publishe
Automated DWI-FLAIR mismatch assessment in stroke using DWI only
No full textsponsorship: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: (Agence Nationale de la Recherche|ANR-18-RHUS-0001, FP7 Health|278276, Socit Franaise de Radiologie|Research grant, Socit Franaise de Neuroradiologie|Research grant)status: Publishe
Signalerende subcellulaire Ca2+ microdomeinen reguleren cardiomyocyt groei en functie
No full textThe cyclic, coordinated contraction and relaxation of cardiomyocytes underlie the heart's pumping action. By linking electrical depolarisation of the sarcolemma during the action potential to myofilament contraction, calcium (Ca2+) is central to the excitation-contraction coupling (ECC) process underlying cardiomyocyte contraction. During ECC, a cell-wide rise in intracellular Ca2+ initiates contraction, while its subsequent clearance enables relaxation, resetting the cell for the next cycle. This global Ca2+ transient is spatially composed of synchronously evoked elementary Ca2+ release events, termed Ca2+ sparks, mediated by ryanodine receptors (RyRs), a class of sarcoplasmic reticulum Ca2+ channels, localised at specialised microdomains called dyads.
Inositol 1,4,5-trisphosphate receptors (IP3Rs), another class of sarcoplasmic reticulum Ca2+ channels, have been shown to modulate ECC, an effect hypothesised to stem from their co-localisation with RyRs in the dyadic microdomain. To test this, we developed a spatial computational model of the dyad to investigate how functional IP3Rs influence Ca2+ dynamics within this microdomain. Simulations revealed that IP3Rs elevate dyadic Ca2+, sensitising proximal RyRs toward activation and thereby promoting spontaneous Ca2+ spark formation. The stochastic gating behaviour of IP3Rs is essential for eliciting this effect.
RyRs are also expressed outside dyads in non-coupled clusters. Confocal and super-resolution imaging have indicated that non-coupled RyR clusters are more prevalent in pathological conditions, with IP3Rs preferentially co-localising with them. To investigate the functional implications of this spatial organisation, we extended the aforementioned computational model to simulate the Ca2+ release behaviour of non-coupled RyR clusters in the presence of neighbouring sparking dyads. Simulations revealed that IP3Rs increased spontaneous Ca2+ release events and enhanced the sensitivity of non-coupled RyRs to Ca2+ diffusing from nearby dyads, thereby improving the synchronicity of Ca2+ release between non-coupled and dyadic RyRs during ECC.
In addition to ECC, Ca2+ also activates the pro-hypertrophic transcription factors NFAT and MEF2, driving gene expression programmes that underlie cardiomyocyte growth and cardiac hypertrophy. The necessity of nuclear Ca2+ for activating these transcription factors has been established, with Ca2+ release from IP3Rs expressed on the nuclear envelope (NE) shown to be sufficient for their activation. However, the nucleoplasm also exhibits Ca2+ fluctuations whose kinetics lag behind that of ECC-associated Ca2+ transients originating from the cytoplasm. The Ca2+-handling mechanisms hypothesised to underlie these ECC-associated nucleoplasmic Ca2+ transients have been indirectly supported, but remain to be biophysically demonstrated. Furthermore, it is unclear how NE-bound IP3Rs modulate nucleoplasmic Ca2+ amidst these transients to encode hypertrophic signalling. To address these gaps, we developed a spatial computational model of the perinuclear region that incorporates NE permeability, nuclear-specific Ca2+ buffering, and NE-bound IP3R activity to simulate nucleocytoplasmic Ca2+ dynamics during ECC. Simulations revealed that NE permeability primarily contributes to the kinetic delay of Ca2+ transients in the nucleoplasm relative to that of the cytoplasm, while NE-bound IP3R activity prolongs the transient's decay to baseline.
Structural remodelling of the nucleus may also influence nucleoplasmic Ca2+ handling. Using transmission electron microscopy, we characterised age- and disease-associated changes in nuclear morphology of cardiomyocytes in a sheep model of pressure overload. Morphometric analyses revealed an increase in nuclear length with age while nuclear shape complexity decreases in young hearts subject to pressure overload, due to a reduction in NE invagination density.
Together, this thesis provides mechanistic insights into the role of IP3Rs in regulating cardiomyocyte function and growth through new computational frameworks and experimental studies. These findings advance our understanding of subcellular Ca2+ signalling in cardiomyocyte pathophysiology.status: Accepte
Students' willingness to engage with feedback from central tests: The influence of cognitive and non-cognitive student characteristics
No full textsponsorship: Department for Education (DFE)|Steunpunt Centrale Toetsen in Onderwijsstatus: Publishe