Issues
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Cover image
Cover Image
Cover: Distribution of lysosomes (LysoTracker positive; red) in a 7-day-old brain (wholemount) of a wild-type Drosophila melanogaster. The nuclei and trachea are stained with DAPI (blue). See article by Onkar et al. (dmm050238). Cover image is licensed under a Creative Commons Attribution 4.0 International license.
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EDITORIAL
Crossroads in virology: current challenges and future perspectives in the age of emerging viruses
Summary: Understanding virus–host interactions at the microscopic and macroscopic scales is key to therapeutic and vaccine development, prediction of viral emergence and prevention of future outbreaks.
A MODEL FOR LIFE
REVIEWS
Nuclear mechanosensing of the aortic endothelium in health and disease
Summary: Endothelial cells are exposed to mechanical forces such as shear stress exerted by blood flow. We explore the emerging role of the nucleus in how these forces are sensed and transduced.
How metals fuel fungal virulence, yet promote anti-fungal immunity
Summary: Transition metals, such as copper, iron and zinc, are critical determinants of host immune responses to fungal pathogens. Paradoxically, metals may also support fungal virulence.
EDITOR'S CHOICE
RESEARCH ARTICLES
Mutation in the FUS nuclear localisation signal domain causes neurodevelopmental and systemic metabolic alterations
Summary: This work reinforces the fundamental role of FUS in neurodevelopment and systemic metabolism and the notion that the FUS gene should be considered in clinical neurodevelopmental genetic testing.
Increase in brain glycogen levels ameliorates Huntington's disease phenotype and rescues neurodegeneration in Drosophila
Summary: Whereas healthy brain contains very little glycogen, aged brains and brains of people with neurodegenerative disorders tend to accumulate glycogen. We demonstrate here that, in the Drosophila model of Huntington's disease, enhancement of glycogen synthesis in fly brain ameliorated the disease phenotype through activation of auto-lysosomal functions.
The roles of JAK2/STAT3 signaling in fusion of the secondary palate
Summary: Inhibition of JAK2/STAT3 results in failure to suppress p63, resulting in defects in palatal fusion. This defect is rescued by p63 haploinsufficiency and by folic acid treatment, reactivating JAK2/STAT3.
Glycosphingolipids are linked to elevated neurotransmission and neurodegeneration in a Drosophila model of Niemann Pick type C
Summary: Genetic analyses in a Drosophila disease model show that loss of Npc1 and glycosphingolipid pathway synthesis elevate glutamatergic neurotransmission within a common functional pathway, and this pathway links to subsequent neurodegeneration.
Microenvironment-dependent growth of Sezary cells in humanized IL-15 mice
Summary: The genetic humanization of IL-15 in immunodeficient host mice uniquely supports the engraftment and growth of Sezary syndrome (SS) patient samples, resulting in the generation of new SS patient-derived xenograft models.
Sodium butyrate does not protect spinal motor neurons from AMPA-induced excitotoxic degeneration in vivo
Summary: In rats with chronic spinal motor neuron death induced by AMPA-mediated excitotoxicity, HDAC4 inhibition through administration of sodium butyrate does not ameliorate paralysis or muscle pathology.
Identification of histone deacetylase inhibitors as neutrophil recruitment modulators in zebrafish using a chemical library screen
Summary: Multiple histone deacetylase inhibitors were identified from a chemical library screen to suppress neutrophil recruitment in a zebrafish injury model. AR-42 modulates neutrophil recruitment by suppressing the transcriptional expression of il1b/cxcl8.
A systematic approach identifies p53-DREAM pathway target genes associated with blood or brain abnormalities
Editor's choice: Putative DREAM-binding sites were identified for 151 genes associated with blood or brain abnormalities and mutation of 21 sites impacted gene expression, suggesting that p53-DREAM alterations contribute to bone marrow failure and glioblastoma cell phenotypes.
Loss of zebrafish pkd1l1 causes biliary defects that have implications for biliary atresia splenic malformation
Summary: PKD1L1-linked biliary atresia is a serious childhood liver disease with no effective therapies. Deletion of zebrafish pkd1l1 results in impaired function and abnormal development of bile ducts in the liver.
Comparative multi-omic analyses of cardiac mitochondrial stress in three mouse models of frataxin deficiency
Summary: The mitochondrial integrated stress response in the heart of a mouse model of Friedreich ataxia is surprisingly mild, despite a severe decrease in frataxin levels below 1% of normal.
Transcriptomic analysis of diabetic kidney disease and neuropathy in mouse models of type 1 and type 2 diabetes
Summary: Transcriptomic profiles from glomeruli and sciatic nerves of type 1 and type 2 diabetes mouse models support a strong influence of inflammation and genetic background on diabetic complications.
RESOURCE ARTICLES
Short tandem repeat profiling via next-generation sequencing for cell line authentication
Summary: Evaluation of next-generation sequencing (NGS)-based short tandem repeat (STR) profiling of human and mouse cell lines in a high-throughput format revealed that STR-NGS is a valuable platform for human and mouse cell line authentication.
Efficient genetic editing of human intestinal organoids using ribonucleoprotein-based CRISPR
Summary: High-efficiency ribonucleoprotein-mediated genome editing enables rapid functional studies in human organoids by avoiding the need for clonal selection.
FIRST PERSON
CORRECTIONS
Correction: Cells expressing PAX8 are the main source of homeostatic regeneration of adult mouse endometrial epithelium and give rise to serous endometrial carcinoma
DMM Journal Meeting 2024: Pre-clinical Modelling of Human Genetic Disease and Therapy

Registration is open for our 2024 Journal Meeting. Rapid advances in gene editing and genetic technologies have revolutionised our ability to model human genetic disease and provided new hope for gene therapies. At this Meeting, speakers will present the very latest advances in modelling human genetic disease.
Moving towards heart success – Disease Models & Mechanisms Special Issue

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Sustainable Conferencing Initiative

Through our Sustainable Conferencing Grants, we promote the use of new technology and greener modes of travel. Our blog posts showcase examples of sustainability in action and share guidance about how new technologies and different conference formats work in practice.