Issues
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Cover image
Cover Image
Cover: Actin and myosin networks, respectively, in magenta and green, of a cardiomyocyte of a Drosophila fly with heart-specific depletion of the frataxin mitochondrial protein. See article by Palandri et al. (dmm033811). Cover image is licensed under a Creative Commons Attribution 4.0 International license.
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REVIEWS
Plasticity of differentiated cells in wound repair and tumorigenesis, part I: stomach and pancreas
Summary: Epithelial cells in diverse tissues have an innate plasticity program (recently dubbed ‘paligenosis’) such that differentiated cells can become regenerative upon large-scale insults to an organ. Thus, the proliferating, regenerative cells in an organ may not always derive directly from stem cells, which invites us to refine theories about the cell of origin of cancer such as the multi-hit model of tumorigenesis.
Probiotics against airway allergy: host factors to consider
Summary: This Review discusses the host factors that influence the outcomes of in vivo probiotic interventions in allergy, focusing on genetics, sex, age and microbiological status in mouse models of allergic disease.
RESEARCH ARTICLES
Orthotopic and heterotopic murine models of pancreatic cancer and their different responses to FOLFIRINOX chemotherapy
Summary: Orthotopic and heterotopic allograft locations confer unique microenvironments that influence growth kinetics, desmoplasia and angiogenesis. These differences translate to differential sensitivities to FOLFIRINOX and should inform future preclinical study design.
Retina-specific loss of Ikbkap/Elp1 causes mitochondrial dysfunction that leads to selective retinal ganglion cell degeneration in a mouse model of familial dysautonomia
Summary: The elongator subunit IKBKAP/ELP1 is not required for development, but is essential for maintaining mitochondrial function and retina morphology. Loss of this subunit causes progressive, selective degeneration of retinal ganglion cells.
Octopamine signaling in the metazoan pathogen Schistosoma mansoni: localization, small-molecule screening and opportunities for drug development
Summary: The nervous system of Schistosoma mansoni has been mapped and the widespread presence of octopamine revealed. The identification of agonists and antagonists of tyrosine-derivative signaling might provide opportunities for drug repurposing.
HIF-1α activation in myeloid cells accelerates dextran sodium sulfate-induced colitis progression in mice
Summary: We challenged myeloid-specific knockout mice targeting the hypoxia-inducible factor (HIF) pathway to dextran sodium sulfate-induced colitis, demonstrating that HIF-1α, but not HIF-2α, activation in myeloid cells regulates colitis severity in mice.
Identification of cardioprotective drugs by medium-scale in vivo pharmacological screening on a Drosophila cardiac model of Friedreich's ataxia
Editor's choice: The first medium-scale pharmacological in vivo screen on a Drosophila cardiac model identified 11 compounds with protective effects on Friedreich's ataxia cardiomyopathy.
Dissecting recipient from donor contribution in experimental kidney transplantation: focus on endothelial proliferation and inflammation
Summary: Using experimental kidney transplantation, we dissected donor graft from recipient environment effects, focusing on the endothelium and inflammation. These results can direct strategies to improve graft survival after suboptimal transplantation.
ZMPSTE24 missense mutations that cause progeroid diseases decrease prelamin A cleavage activity and/or protein stability
Summary: The zinc metalloprotease ZMPSTE24 performs the final step of prelamin A processing. Here, a yeast-based system shows differences in protein stability and activity for alleles of ZMPSTE24 that cause progeria disease.
Cerebellar synapse properties and cerebellum-dependent motor and non-motor performance in Dp71-null mice
Summary: Dp71 is the most prominent dystrophin gene product in the adult brain. Here, multiple approaches including behavioral tests and electrophysiology are adopted to explore the role of Dp71 in the cerebellum.
Transcriptional upregulation of Bag3, a chaperone-assisted selective autophagy factor, in animal models of KY-deficient hereditary myopathy
Summary: Increased transcriptional activation of the tension-mediated autophagy factor Bag3 is shown to be a consistent molecular hallmark of KY deficiency in animal models.
Fetal articular cartilage regeneration versus adult fibrocartilaginous repair: secretome proteomics unravels molecular mechanisms in an ovine model
Summary: Secretome proteomics identifies differential regulation of inflammation modulators during fetal and adult articular cartilage defect healing, offering novel strategies for therapy.
Identification of brain metastasis genes and therapeutic evaluation of histone deacetylase inhibitors in a clinically relevant model of breast cancer brain metastasis
Summary: The authors introduce a new syngeneic mouse model of spontaneous breast cancer brain metastasis, demonstrate its phenotypic, functional and transcriptomic relevance to human TNBC brain metastasis, and test novel therapies.
Use of sodium 4-phenylbutyrate to define therapeutic parameters for reducing intracerebral hemorrhage and myopathy in Col4a1 mutant mice
Summary: COL4A1 mutations cause a multisystem disorder by impairing secretion of COL4A1/A2 heterotrimers. We define parameters for reducing stroke and myopathy in Col4a1 mutant mice by pharmacologically promoting heterotrimer secretion.
RESOURCE ARTICLE
Recapitulating muscle disease phenotypes with myotonic dystrophy 1 induced pluripotent stem cells: a tool for disease modeling and drug discovery
Summary: This work provides proof of principle for the use of myotonic dystrophy 1 patient-specific induced pluripotent stem cells to model muscle pathology in vitro and in drug discovery.
PREPRINT HIGHLIGHTS
Virtual Meeting - Developmental Disorders: From Mechanism to Treatment
A collaboration between the Development and Disease Models & Mechanisms journal teams, this virtual Meeting will unite developmental biologists, human geneticists and clinical researchers to focus on building bridges from bench to clinic. Register your interest and find out more.
High-dose vitamin B1 therapy prevents the development of experimental fatty liver driven by overnutrition
Vitamin B1 is shown to prevent nutrition-induced fatty liver in our current Editor’s choice by Hay Davir and his colleagues, when they use sheep as a large-animal model for studying the disease.
Find out more in an interview with the paper's first authors, Mugagga Kalyesubula and Ramgopal Mopuri.
Upcoming grant deadlines
Grants awarded by The Company of Biologists help scientists travel, attend events and host sustainable activities. Make a note of the upcoming application deadlines and find out more about the grants on offer:
DMM Conference Travel Grants
17 May 2021
Sustainable Conferencing Grants
17 May 2021
Travelling Fellowships
31 May 2021
Scientific Meeting Grants
4 June 2021
Call for papers - The RAS Pathway: Diseases, Therapeutics and Beyond
Our upcoming special issue is welcoming submissions until 3 May 2021. Guest-edited by Donita Brady (Perelman School of Medicine at the University of Pennsylvania, USA) and Arvin Dar (Icahn School of Medicine at Mount Sinai, USA), the issue will focus on targeting the RAS pathway.