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SPECIAL ARTICLE

Summary: Large-scale, focused phenotyping campaigns provide data for thousands of mutant mouse genes, yielding key information for understanding rare human diseases and for developing novel drug therapies.

REVIEW

Summary: This Review summarizes some of the exciting work that has used Drosophila as a model for the ever-expanding field of intellectual disability and autism spectrum disorders. It highlights disease-relevant assays, emerging themes and future challenges.

RESEARCH ARTICLES

Editor's choice: Using Drosophila as a low-complexity model for human myeloproliferative neoplasms, the authors identified a conserved mechanism by which the Tip60 lysine acetyltransferase acts as a tumor suppressor by repressing JAK protein expression in a histone-independent manner.

Summary: FGFR2 gain-of-function mutations differentially affect cartilage formation and intramembranous ossification of dermal bone, resulting in abnormal embryonic osteogenesis of the mandible.

Summary: In a zebrafish model for inflammation, glucocorticoids do not affect the migration of macrophages, but inhibit their differentiation towards an M1 phenotype, by strongly attenuating transcriptional responses in these cells.

Summary: Deep brain stimulation in the subthalamic nucleus in rats with a unilateral dopaminergic lesion established a new functional interhemispheric striatal network.

Summary: The roles of DYRK1A in angiogenesis and maintenance of the developing cerebral vasculature mediated by calcium signaling were revealed using zebrafish dyrk1aa knockout mutants.

Summary: The authors present a mechanistic model to understand how alterations of the membrane architecture by the progressive accumulation of sphingolipids undermines basic cell function, with potential implications for a variety of genetic sphingolipidoses and adult neurodegenerative conditions.

Summary: Loss of synaptic GluR1, and reduced excitability within pyramidal neurons, implicates hypoexcitability and attenuated synaptic function in the pathogenic decline of neuronal function in TDP-43-associated ALS.

Summary: Fibrotic deposition and PH are inhibited by the FDA-approved drug hymecromone, suggesting hyaluronan synthesis inhibition as a potential therapy for CPFE and highlighting a novel mechanism through HAS3-positive macrophages.

Summary: Homozygous loss of asxl1 in zebrafish leads to apoptosis of newly formed HSCs by upregulation of bim and bid. Half of the asxl1+/− zebrafish had MPNs by 5 months of age.

Summary: The beneficial effects of exercise against diet-induced early obesity and NAFLD are mediated by its capacity to modulate intestinal microbiota composition and functionality, restore lipid metabolism and prevent disruption of the gut-liver axis.

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