Results 61 to 70 of about 321,270 (256)

Targeting social learning and engagement

Environmental modelling & software, 2020
Serious games and gamification are useful tools for learning and sustaining long-term engagement in the activities that are not meant to be entertaining. However, the application of game design in the participatory modeling context remains fragmented and mostly limited to user-friendly interfaces, storytelling, and visualization for better ...
Bakhanova, Elena, Garcia, Jaime A., Raffe, William L., Voinov, Alexey   +3 more
openaire   +1 more source

Structural insights and therapeutic targets in Acinetobacter baumannii capsule biosynthesis

FEBS Letters, EarlyView.
Hypervirulent KL49 A. baumannii's capsular polysaccharide contains the nonulosonic acid 8‐epi‐Leg5,7Ac2, synthesized by epimerization via ElaA, ElaB, and ElaC. Crystal structures of ElaA, ElaB, and ElaC reveal their role in CMP‐Leg5,7Ac2 synthesis and regioselective C8 epimerization.
Woo Cheol Lee, Junho Jeong, Chae Yeong Lee, Hyunjoon Cho, Man Hwan Oh, Je Chul Lee, Jee‐Young Lee, Yangmee Kim   +7 more
wiley   +1 more source

Chemical genetics strategy to profile kinase target engagement reveals role of FES in neutrophil phagocytosis

Nature Communications, 2020
Chemical tools to monitor drug-target engagement of endogenous enzymes are essential for preclinical target validation. Here, the authors present a chemical genetics strategy to study target engagement of endogenous kinases, achieving specific labeling ...
Tom van der Wel, Riet Hilhorst, Hans den Dulk, Tim van den Hooven, Nienke M. Prins, Joost A. P. M. Wijnakker, Bogdan I. Florea, Eelke B. Lenselink, Gerard J. P. van Westen, Rob Ruijtenbeek, Herman S. Overkleeft, Allard Kaptein, Tjeerd Barf, Mario van der Stelt   +13 more
doaj   +1 more source

α‐Synuclein aggregation landscape from phase separation to neurotoxic intermediates

FEBS Letters, EarlyView.
Alpha‐synuclein aggregation in Parkinson's disease involves a complex landscape of transient intermediates, including oligomers, fibrils and liquid–liquid phase separation (LLPS). A view is emerging in which LLPS maturation into solid‐like condensates may contribute to the formation of neurotoxic species.
Silvia Arino, Giuliana Fusco, Alfonso De Simone   +2 more
wiley   +1 more source

Three phosphatase families form a community: The phosphohydrolases that act upon inositol pyrophosphates

FEBS Letters, EarlyView.
Inositol pyrophosphates are energy‐rich signaling molecules that perform critical functions in cells. Three different families of phosphatases hydrolyze the β phosphate of the inositol pyrophosphate molecules: two have narrow specificities and one is promiscuous.
Ronda J. Rolfes
wiley   +1 more source

Design and analysis strategies for robust microbiome ageing research

FEBS Letters, EarlyView.
The gut microbiome changes with age and associates with age‐related morbidity and mortality, establishing it as a potential biomarker and intervention target for ageing. Realising this potential requires methodological rigour, yet distinguishing biological signals from methodological artefacts remains challenging across cohorts. This review provides an
Mark Olenik, İsmail Güderer, Yi Wang, Tayyaba Alvi, Prasoon Pandey, Handan Melike Dönertaş   +5 more
wiley   +1 more source

When to consider intra-target microdosing: physiologically based pharmacokinetic modeling approach to quantitatively identify key factors for observing target engagement

Frontiers in Pharmacology
Intra-Target Microdosing (ITM), integral to Phase 0 clinical studies, offers a novel approach in drug development, effectively bridging the gap between preclinical and clinical phases.
Yasunori Aoki, Yasunori Aoki, Malcom Rowland, Yuichi Sugiyama, Yuichi Sugiyama   +4 more
doaj   +1 more source

Mixed‐class J‐domain protein scaffolds promote expanded aggregate handling and multivalent Hsp70 engagement during functional disaggregase assembly

FEBS Letters, EarlyView.
Protein aggregates threaten proteostasis and cell health. In human cells, Hsp70–J‐domain protein‐based disaggregases remove aggregates, but how they assemble remains unclear. Our biochemical findings show that DNAJA2‐ and DNAJB1‐containing disaggregase scaffolds enhance luciferase aggregate targeting, and that Hsp70 recruitment by both J‐domain ...
Anna Szlachcic, Nadinath B. Nillegoda
wiley   +1 more source

Investigating transcription factor dynamics in health and disease using FRAP

FEBS Letters, EarlyView.
FRAP analysis of GFP‐tagged transcription factors reveals how molecular mobility and target engagement change in response to drug treatment. By combining live‐cell imaging, quantitative model fitting, and statistical analysis, this approach uncovers transcription factor dynamics linked to disease mechanisms, providing a powerful framework for ...
Kannan Govindaraj, Carolina Vazquez Garzon, Jose Joaquin Velasco, Janine N. Post   +3 more
wiley   +1 more source

Tumour–host interactions in Drosophila: mechanisms in the tumour micro‐ and macroenvironment

Molecular Oncology, EarlyView.
This review examines how tumour–host crosstalk takes place at multiple levels of biological organisation, from local cell competition and immune crosstalk to organism‐wide metabolic and physiological collapse. Here, we integrate findings from Drosophila melanogaster studies that reveal conserved mechanisms through which tumours hijack host systems to ...
José Teles‐Reis, Tor Erik Rusten
wiley   +1 more source