Issues
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Cover image
Cover Image
Cover: Expression of phenylalanyl tRNA synthetase subunit alpha (α-PheRS) twin-spot clones in the follicle cells of the fly ovary. Twin spot clones were generated with the wild-type α-PheRS clone (blue) expressing normal endogenous levels as internal control, and its twin clone expressing elevated levels of α-PheRS (orange). See article by Ho et al. (dmm048132). Cover image is licensed under a Creative Commons Attribution 4.0 International license.
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REVIEWS
Mending a broken heart: In vitro, in vivo and in silico models of congenital heart disease
Summary:In vitro, in vivo and in silico models of congenital heart disease provide important insights into the causes, evolution and pathological effects of congenital structural heart disease – a group of largely heterogenous disorders with substantial morbidity – and aid in designing effective therapies.
Modelling epilepsy in the mouse: challenges and solutions
Summary: This Review discusses the challenges of modelling epilepsy in mice, a condition in which the outward manifestation of the disorder appears only sporadically, and reviews possible solutions encompassing both genetic and induced models.
RESEARCH ARTICLES
Modulation of serotonin in the gut-liver neural axis ameliorates the fatty and fibrotic changes in non-alcoholic fatty liver
Summary: The gut-liver neural axis is involved in NAFLD progression and serotonin is the key factor in allowing this pathway to change the expression of tight junction molecules, microbiota diversity and short-chain fatty acids.
Hyperuricemia causes kidney damage by promoting autophagy and NLRP3-mediated inflammation in rats with urate oxidase deficiency
Summary: We established a RISPR/Cas9-mediated Uox gene-KO Wistar rat model of hyperuricemia, and show that autophagy and NLRP3-related inflammation are involved in uric acid nephropathy.
Transformed notochordal cells trigger chronic wounds in zebrafish, destabilizing the vertebral column and bone homeostasis
Summary: Analyses using a zebrafish line expressing RAS in the notochord, under the control of the kita promoter, revealed that transformed notochord cells alter the skeleton during life, causing a wound-like phenotype and activating chronic wound response.
Murine myeloid cell MCPIP1 suppresses autoimmunity by regulating B-cell expansion and differentiation
Summary: Analyses of mice deficient in myeloid MCPIP1 reveal a function of myeloid MCPIP1 in the transition from autoinflammation to autoimmunity and a role for macrophage-dependent immune activation as a trigger of secondary autoimmunity.
High-dose vitamin B1 therapy prevents the development of experimental fatty liver driven by overnutrition
Editor's choice: Experiments using overnourished sheep raised on a high-calorie liver-fattening diet, treated with and without thiamine, revealed that vitamin B1 protects against the development of fatty liver driven by overnutrition.
A translation-independent function of PheRS activates growth and proliferation in Drosophila
Summary: A moonlighting activity of the α-subunit of the Phenylalanyl tRNA synthetase in Drosophila promotes growth and proliferation through a novel mechanism that neither involves aminoacylation nor translation.
EZH2 is required for parathyroid and thymic development through differentiation of the third pharyngeal pouch endoderm
Summary: EZH2 in the pharyngeal apparatus is required in the endoderm for the development of the parathyroids and thymus, and positively regulates the expression of the Tbx1 gene.
NODAL/TGFβ signalling mediates the self-sustained stemness induced by PIK3CAH1047R homozygosity in pluripotent stem cells
Summary: Transcriptomic and proteomic analyses of iPSCs with allele-dose dependent expression of the PIK3CAH1047R oncogene confirm network rewiring in homozygous mutants, with self-sustained stemness likely driven by constitutive TGFβ/NODAL pathway activation.
RESOURCE ARTICLE
Multiscale molecular profiling of pathological bone resolves sexually dimorphic control of extracellular matrix composition
Summary: Combined application of polarisation-resolved second-harmonic generation microscopy and Raman spectroscopy identified unique, sexually dimorphic extracellular matrix signatures linking pathological matrix disorganisation with composition.
FIRST PERSON
DMM Journal Meeting 2023: Infectious Diseases Through an Evolutionary Lens

The abstract submission deadline for our 2023 Journal Meeting ‘Infectious Diseases Through an Evolutionary Lens’ is 14 July 2023. Find out more and register here.
The Forest of Biologists

The Forest of Biologists is a biodiversity initiative created by The Company of Biologists, with support from the Woodland Trust. For every Research and Review article published in Disease Models & Mechanisms a native tree is planted in a UK forest. In addition to this we are protecting and restoring ancient woodland and are dedicating these trees to our peer reviewers. Visit our virtual forest to learn more.
Propose a new Workshop for 2025

Do you have an idea for a Workshop? If so, click here. We are now accepting proposals for our 2025 Workshops programme. As the scientific organiser, your involvement will be focused on the science. We'll take care of all the logistics. In 2025 we'll continue our efforts to diversify our Workshop programme and will be reserving one of our Workshops for an application from a Global South country to host an event overseas.
At a Glance - in vitro cardiac models

In our recent At a Glance feature Lika Drakhlis and Robert Zweigerdt provide an overview of in vitro cardiac models, their advantages and limitations and their applications for disease modelling and therapeutic development.
Perspective - Designer pigs for xenogeneic heart transplantation and beyond

Xenotransplantation of porcine hearts is a potential option for patients who cannot receive human organs. Eckhard Wolf and colleagues elaborate on how genetically engineered pigs can provide a powerful platform for restoration of cardiac function.