A novel Cre-enabled tetracycline-inducible transgenic system for tissue-specific cytokine expression in the zebrafish: CETI-PIC3 [RESOURCE ARTICLE]
This article has an associated First Person interview with the first author of the paper. (Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - June 25, 2020 Category: Biomedical Science Authors: Ibrahim, S., Harris-Kawano, A., Haider, I., Mirmira, R. G., Sims, E. K., Anderson, R. M. Tags: Zebrafish as a Disease Model RESOURCE ARTICLE Source Type: research

Precision-based modeling approaches for necrotizing enterocolitis [REVIEW]
ABSTRACT Necrotizing enterocolitis (NEC) is the leading cause of death from gastrointestinal disease in premature infants and remains stubbornly difficult to treat in many cases. Much of our understanding of NEC pathogenesis has been gained through the study of highly translational animal models. However, most models of NEC are limited by their overall complexity and by the fact that they do not incorporate human tissue. To address these limitations, investigators have recently developed precision-based ex vivo models of NEC, also termed ‘NEC-in-a-dish’ models, which provide the opportunity to increase our unde...
Source: DMM Disease Models and Mechanisms - June 23, 2020 Category: Biomedical Science Authors: Kovler, M. L., Sodhi, C. P., Hackam, D. J. Tags: Organoids, Model Systems in Drug Discovery REVIEW Source Type: research

Zebrafish models of skeletal dysplasia induced by cholesterol biosynthesis deficiency [RESEARCH ARTICLE]
ABSTRACT Human disorders of the post-squalene cholesterol biosynthesis pathway frequently result in skeletal abnormalities, yet our understanding of the mechanisms involved is limited. In a forward-genetic approach, we have found that a late-onset skeletal mutant, named kolibernu7, is the result of a cis-acting regulatory mutation leading to loss of methylsterol monooxygenase 1 (msmo1) expression within pre-hypertrophic chondrocytes. Generated msmo1nu81 knockdown mutation resulted in lethality at larval stage. We demonstrated that this is a result of both cholesterol deprivation and sterol intermediate accumulation by crea...
Source: DMM Disease Models and Mechanisms - June 23, 2020 Category: Biomedical Science Authors: Anderson, R. A., Schwalbach, K. T., Mui, S. R., LeClair, E. E., Topczewska, J. M., Topczewski, J. Tags: Zebrafish as a Disease Model RESEARCH ARTICLE Source Type: research

Extracellular matrix induced by steroids and aging through a G-protein-coupled receptor in a Drosophila model of renal fibrosis [RESEARCH ARTICLE]
ABSTRACT Aldosterone is produced by the mammalian adrenal cortex to modulate blood pressure and fluid balance; however, excessive, prolonged aldosterone promotes fibrosis and kidney failure. How aldosterone triggers disease may involve actions independent of its canonical mineralocorticoid receptor. Here, we present a Drosophila model of renal pathology caused by excess extracellular matrix formation, stimulated by exogenous aldosterone and by insect ecdysone. Chronic administration of aldosterone or ecdysone induces expression and accumulation of collagen-like Pericardin in adult nephrocytes – podocyte-like cells th...
Source: DMM Disease Models and Mechanisms - June 23, 2020 Category: Biomedical Science Authors: Zheng, W., Ocorr, K., Tatar, M. Tags: Drosophila as a Disease Model RESEARCH ARTICLE Source Type: research

Labs in the time of COVID: an early-career scientist's view [EDITORIAL]
ABSTRACT The outbreak of COVID-19 has stalled both the basic, clinical and non-COVID medical research. The scientific community has shown extraordinary flexibility and resilience in responding to the pandemic. However, funding restructuring, risk of infection, cancelation of scientific conferences and delayed experiments have already proven detrimental to the career opportunities of early-career scientists. Moreover, school closures and a lack of systematic support for childcare have been additional challenges for early- and mid-career researchers who have young children. This Editorial describes an early-career researcher...
Source: DMM Disease Models and Mechanisms - June 22, 2020 Category: Biomedical Science Authors: Chuang, L.-s. Tags: EDITORIAL Source Type: research

Biomimetic device and foreign body reaction cooperate for efficient tumour cell capture in murine advanced ovarian cancer [RESEARCH ARTICLE]
In this study, we integrated the concept of creating an artificial niche to capture tumour cells actively disseminating in the peritoneal cavity with a therapeutic strategy modulating the interactions of metastatic cells with the ECM. The aim was to transform a disseminated disease into a focal disease. For this, we designed and developed a ‘biomimetic’ ECM composed of a nonresorbable three-dimensional scaffold with collagen coating and characterized the FBR to the implanted biomaterial. We also analysed the safety of the implanted devices and their ability to capture tumour cells in different murine preclinica...
Source: DMM Disease Models and Mechanisms - June 16, 2020 Category: Biomedical Science Authors: Alonso-Alconada, L., de la Fuente, A., Santacana, M., Ferreiros, A., Lopez-Lopez, R., Matias-Guiu, X., Abal, M. Tags: Cancer RESEARCH ARTICLE Source Type: research

First person - Amelie Bacle [FIRST PERSON]
ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping early-career researchers promote themselves alongside their papers. Amélie Bacle is first author on ‘A comprehensive study of phospholipid fatty acid rearrangements in metabolic syndrome: correlations with organ dysfunction’, published in DMM. Amélie conducted the research described in this article while a postdoc in Thierry Ferreira’s lab at Université de Poitiers, Poitiers, France, where she investigated lipid membranes, their composit...
Source: DMM Disease Models and Mechanisms - June 14, 2020 Category: Biomedical Science Tags: FIRST PERSON Source Type: research

Understanding the impact of fibroblast heterogeneity on skin fibrosis [REVIEW]
ABSTRACT Tissue fibrosis is the deposition of excessive extracellular matrix and can occur as part of the body's natural wound healing process upon injury, or as a consequence of diseases such as systemic sclerosis. Skin fibrosis contributes to significant morbidity due to the prevalence of injuries resulting from trauma and burn. Fibroblasts, the principal cells of the dermis, synthesize extracellular matrix to maintain the skin during homeostasis and also play a pivotal role in all stages of wound healing. Although it was previously believed that fibroblasts are homogeneous and mostly quiescent cells, it has become incre...
Source: DMM Disease Models and Mechanisms - June 14, 2020 Category: Biomedical Science Authors: Griffin, M. F., desJardins-Park, H. E., Mascharak, S., Borrelli, M. R., Longaker, M. T. Tags: REVIEW Source Type: research

A comprehensive study of phospholipid fatty acid rearrangements in metabolic syndrome: correlations with organ dysfunction [RESEARCH ARTICLE]
This article has an associated First Person interview with the first author of the paper. (Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - June 14, 2020 Category: Biomedical Science Authors: Bacle, A., Kadri, L., Khoury, S., Ferru-Clement, R., Faivre, J.-F., Cognard, C., Bescond, J., Krzesiak, A., Contzler, H., Delpech, N., Colas, J., Vandebrouck, C., Sebille, S., Ferreira, T. Tags: Metabolic Disorders RESEARCH ARTICLE Source Type: research

First person - Malabika Chakrabarti [FIRST PERSON]
ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping early-career researchers promote themselves alongside their papers. Malabika Chakrabarti is first author on ‘Targeted repression of Plasmodium apicortin by host microRNA impairs malaria parasite growth and invasion’, published in DMM. Malabika is a PhD student in the lab of Dr Shailja Singh at Jawaharlal Nehru University, New Delhi, India, investigating the functional roles of human microRNA in the pathogenicity of the malaria parasite. (Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - June 2, 2020 Category: Biomedical Science Tags: FIRST PERSON Source Type: research

Targeted repression of Plasmodium apicortin by host microRNA impairs malaria parasite growth and invasion [RESEARCH ARTICLE]
This article has an associated First Person interview with the first author of the paper. (Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - June 2, 2020 Category: Biomedical Science Authors: Chakrabarti, M., Garg, S., Rajagopal, A., Pati, S., Singh, S. Tags: RESEARCH ARTICLE Source Type: research

Frameshift mutations of YPEL3 alter the sensory circuit function in Drosophila [RESEARCH ARTICLE]
ABSTRACT A frameshift mutation in Yippee-like (YPEL) 3 was recently found from a rare human disorder with peripheral neurological conditions including hypotonia and areflexia. The YPEL gene family is highly conserved from yeast to human, but its members’ functions are poorly defined. Moreover, the pathogenicity of the human YPEL3 variant is completely unknown. We generated a Drosophila model of human YPEL3 variant and a genetic null allele of Drosophila homolog of YPEL3 (referred to as dYPEL3). Gene-trap analysis suggests that dYPEL3 is predominantly expressed in subsets of neurons, including larval nociceptors. Anal...
Source: DMM Disease Models and Mechanisms - June 2, 2020 Category: Biomedical Science Authors: Kim, J. H., Singh, M., Pan, G., Lopez, A., Zito, N., Bosse, B., Ye, B. Tags: Drosophila as a Disease Model RESEARCH ARTICLE Source Type: research

Genetic activation of Nrf2 reduces cutaneous symptoms in a murine model of Netherton syndrome [RESEARCH ARTICLE]
This article has an associated First Person interview with the first author of the paper. (Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - May 31, 2020 Category: Biomedical Science Authors: Muzumdar, S., Koch, M., Hiebert, H., Bapst, A., Gravina, A., Bloch, W., Beer, H.-D., Werner, S., Schäfer, M. Tags: Rare diseases RESEARCH ARTICLE Source Type: research

First person - Sukalp Muzumdar [FIRST PERSON]
ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping early-career researchers promote themselves alongside their papers. Sukalp Muzumdar is first author on ‘Genetic activation of Nrf2 reduces cutaneous symptoms in a murine model of Netherton syndrome’, published in DMM. Sukalp conducted the research described in this article while a PhD student in the lab of Prof. Dr Sabine Werner and PD Dr Matthias Schäfer at ETH Zurich, Zurich, Switzerland. He is now a postdoctoral fellow in the lab of Jesse Gillis at Cold...
Source: DMM Disease Models and Mechanisms - May 28, 2020 Category: Biomedical Science Tags: FIRST PERSON Source Type: research

Loss of PRSS56 function leads to ocular angle defects and increased susceptibility to high intraocular pressure [RESEARCH ARTICLE]
ABSTRACT Glaucoma is a leading cause of blindness, affecting up to 70 million people worldwide. High intraocular pressure (IOP) is a major risk factor for glaucoma. It is well established that inefficient aqueous humor (AqH) outflow resulting from structural or functional alterations in ocular drainage tissues causes high IOP, but the genes and pathways involved are poorly understood. We previously demonstrated that mutations in the gene encoding the serine protease PRSS56 induces ocular angle closure and high IOP in mice and identified reduced ocular axial length as a potential contributing factor. Here, we show that Prss...
Source: DMM Disease Models and Mechanisms - May 28, 2020 Category: Biomedical Science Authors: Labelle-Dumais, C., Pyatla, G., Paylakhi, S., Tolman, N. G., Hameed, S., Seymens, Y., Dang, E., Mandal, A. K., Senthil, S., Khanna, R. C., Kabra, M., Kaur, I., John, S. W. M., Chakrabarti, S., Nair, K. S. Tags: RESEARCH ARTICLE Source Type: research