Summary: In anticipation of our upcoming Special Issue, ‘Translating Multiscale Research in Rare Disease’, we celebrate the strides taken in rare disease research that are improving patient diagnosis, prognosis and treatment.
Summary: We believe that increasing opportunities for scientists in low- and middle-income countries will translate to more impactful research done in these countries that inherently includes more samples from diverse populations.
Summary: Unconstrained tissue repair can lead to cancer. We explore how NOTCH signalling promotes ductular regeneration while asking whether it can be inhibited to limit tumour growth.
Glucocorticoid receptor regulates protein chaperone, circadian clock and affective disorder genes in the zebrafish brain
Summary: This study identifies molecular pathways through which the glucocorticoid receptor (GR) mediates stress responses in the zebrafish brain, providing further support for GR-mutant zebrafish as an affective disorder model.
Modeling a variant of unknown significance in the Drosophila ortholog of the human cardiogenic gene NKX2.5
Summary: A variant of unknown clinical significance of a human cardiogenic gene was modeled in Drosophila. In vitro assays showed defects in protein function, and mutation in vivo revealed defects in heart structure.
AGAP1-associated endolysosomal trafficking abnormalities link gene–environment interactions in neurodevelopmental disorders
Summary: AGAP1 deletion variants were identified in three individuals with neurodevelopmental disorders, and, using a loss-of-function Drosophila model, we show that AGAP1 disruption impairs neuronal endolysosomal trafficking and chronically activates the stress response.
DPH1 and DPH2 variants that confer susceptibility to diphthamide deficiency syndrome in human cells and yeast models
Summary: Diphthamide deficiency syndrome is caused by mutations in DPH genes. Analyses in human cell and yeast models identified functionally compromised missense alleles of human DPH1 and DPH2.
OPA1 deficiency impairs oxidative metabolism in cycling cells, underlining a translational approach for degenerative diseases
Summary: This study highlights the effects of OPA1 deficiency on oxidative metabolism in replicative cells and the use of a mathematical model in a translational process in a neurodegenerative context.
Summary: Cells involved in corneal stroma repair originate from corneal keratocytes. Corneal fibroblasts, originating from keratocytes, can regress to a keratocyte phenotype if relocated to a normal matrix.
The dual lipid desaturase/hydroxylase DEGS2 controls phytoceramide levels necessary to counter intestinal inflammation
Editor's choice: The dual lipid desaturase/hydroxylase DEGS2 contributes to mouse intestinal homeostasis and ameliorates colitis by converting dihydroceramides to phytoceramides. Without this enzyme, intestinal epithelial cells have diminished regenerative capacity.
The Drosophila homolog of APP promotes Dscam expression to drive axon terminal growth, revealing interaction between Down syndrome genes
Summary: Down syndrome is caused by an extra copy of human chromosome 21 (HSA21). This study reveals that the interaction between two HSA21 genes is important for axon development.
IL-33 regulates Müller cell-mediated retinal inflammation and neurodegeneration in diabetic retinopathy
Summary: IL-33 is upregulated in Müller cells of murine retina during experimental diabetes, and deletion of IL-33 promotes gliosis, inflammation and neurodegeneration during streptozotocin-induced diabetic retinopathy.
Summary: A zebrafish model of Tango2 deficiency provides insights into key disease processes and the impacts of specific defects on predisposition to environmental triggers in rhabdomyolysis in TANGO2-related disorders.
Blood levels of neurofilament light are associated with disease progression in a mouse model of spinocerebellar ataxia type 3
Summary: Peripheral blood of YACQ84 mice, a model of spinocerebellar ataxia type 3, exhibits increased neuronal-specific NfL, directly associated with disease progression, providing a biomarker to interrogate in preclinical therapeutic studies.
Altered expression, but small contribution, of the histone demethylase KDM6A in obstructive uropathy in mice
Summary: Tubule cell KDM6A expression is increased from a sex-determined baseline in obstructive uropathy. However, knockout of KDM6A in male mice causes only subtle changes, characterized by augmented inflammation.