First person - Laura Tamberg [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. Laura Tamberg is first author on ‘Daughterless, the Drosophila orthologue of TCF4, is required for associative learning and maintenance of the synaptic proteome’, published in DMM. Laura is a PhD student in the lab of Tõnis Timmusk at the Tallinn University of Technology, Tallinn, Estonia. Her research involves investigating the use of Drosophila melanogaster as a model system to understand...
Source: DMM Disease Models and Mechanisms - July 30, 2020 Category: Biomedical Science Tags: FIRST PERSON Source Type: research

First person - Jenny Vermeer and Jonathan lent [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. Jenny Vermeer and Jonathan lent are co-first authors on ‘A lineage-tracing tool to map the fate of hypoxic tumour cells’, published in DMM. Jenny conducted the research described in this article while a postdoctoral researcher in the lab of Ruth Muschel at the University of Oxford, Oxford, UK. She is now a project leader in the lab of Miranda van der Lee at Byondis, Nijmegen, The Netherlands, inve...
Source: DMM Disease Models and Mechanisms - July 30, 2020 Category: Biomedical Science Tags: FIRST PERSON Source Type: research

A lineage-tracing tool to map the fate of hypoxic tumour cells [RESEARCH ARTICLE]
This article has an associated First Person interview with the joint first authors of the paper. (Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - July 30, 2020 Category: Biomedical Science Authors: Vermeer, J. A. F., Ient, J., Markelc, B., Kaeppler, J., Barbeau, L. M. O., Groot, A. J., Muschel, R. J., Vooijs, M. A. Tags: Cancer metabolism RESEARCH ARTICLE Source Type: research

Ciliogenesis and Hedgehog signalling are suppressed downstream of KRAS during acinar-ductal metaplasia in mouse [RESEARCH ARTICLE]
ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths worldwide, but has a 5-year survival rate of only 7% primarily due to late diagnosis and ineffective therapies. To treat or even prevent PDAC, it is vital that we understand the initiating events that lead to tumour onset. PDAC develops from preneoplastic lesions, most commonly pancreatic intraepithelial neoplasias (PanINs), driven by constitutive activation of KRAS. In patients, PanINs are associated with regions of acinar-to-ductal metaplasia (ADM) where, in response to inflammation, acini dedifferentiate to a pancreatic ...
Source: DMM Disease Models and Mechanisms - July 30, 2020 Category: Biomedical Science Authors: Bangs, F. K., Miller, P., O'Neill, E. Tags: Cancer RESEARCH ARTICLE Source Type: research

Early evidence of delayed oligodendrocyte maturation in the mouse model of mucolipidosis type IV [RESEARCH ARTICLE]
ABSTRACT Mucolipidosis type IV (MLIV) is a lysosomal disease caused by mutations in the MCOLN1 gene that encodes the endolysosomal transient receptor potential channel mucolipin-1, or TRPML1. MLIV results in developmental delay, motor and cognitive impairments, and vision loss. Brain abnormalities include thinning and malformation of the corpus callosum, white-matter abnormalities, accumulation of undegraded intracellular ‘storage’ material and cerebellar atrophy in older patients. Identification of the early events in the MLIV course is key to understanding the disease and deploying therapies. The Mcoln1&ndash...
Source: DMM Disease Models and Mechanisms - July 30, 2020 Category: Biomedical Science Authors: Mepyans, M., Andrzejczuk, L., Sosa, J., Smith, S., Herron, S., DeRosa, S., Slaugenhaupt, S. A., Misko, A., Grishchuk, Y., Kiselyov, K. Tags: Neurodegenerative disorders RESEARCH ARTICLE Source Type: research

Daughterless, the Drosophila orthologue of TCF4, is required for associative learning and maintenance of the synaptic proteome [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 - July 30, 2020 Category: Biomedical Science Authors: Tamberg, L., Jaago, M., Säälik, K., Sirp, A., Tuvikene, J., Shubina, A., Kiir, C. S., Nurm, K., Sepp, M., Timmusk, T., Palgi, M. Tags: Developmental Disorders, Drosophila as a Disease Model RESEARCH ARTICLE Source Type: research

Rabbit model of Staphylococcus aureus implant-associated spinal infection [RESOURCE ARTICLE]
ABSTRACT Post-surgical implant-associated spinal infection is a devastating complication commonly caused by Staphylococcus aureus. Biofilm formation is thought to reduce penetration of antibiotics and immune cells, contributing to chronic and difficult-to-treat infections. A rabbit model of a posterior-approach spinal surgery was created, in which bilateral titanium pedicle screws were interconnected by a plate at the level of lumbar vertebra L6 and inoculated with a methicillin-resistant S. aureus (MRSA) bioluminescent strain. In vivo whole-animal bioluminescence imaging (BLI) and ex vivo bacterial cultures demonstrated a...
Source: DMM Disease Models and Mechanisms - July 28, 2020 Category: Biomedical Science Authors: Gordon, O., Miller, R. J., Thompson, J. M., Ordonez, A. A., Klunk, M. H., Dikeman, D. A., Joyce, D. P., Ruiz-Bedoya, C. A., Miller, L. S., Jain, S. K. Tags: RESOURCE ARTICLE Source Type: research

Mitochondrial damage and senescence phenotype of cells derived from a novel frataxin G127V point mutation mouse model of Friedreich's ataxia [RESEARCH ARTICLE]
ABSTRACT Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused by reduced expression of the mitochondrial protein frataxin (FXN). Most FRDA patients are homozygous for large expansions of GAA repeat sequences in intron 1 of FXN, whereas a fraction of patients are compound heterozygotes, with a missense or nonsense mutation in one FXN allele and expanded GAAs in the other. A prevalent missense mutation among FRDA patients changes a glycine at position 130 to valine (G130V). Herein, we report generation of the first mouse model harboring an Fxn point mutation. Changing the evolutiona...
Source: DMM Disease Models and Mechanisms - July 27, 2020 Category: Biomedical Science Authors: Fil, D., Chacko, B. K., Conley, R., Ouyang, X., Zhang, J., Darley-Usmar, V. M., Zuberi, A. R., Lutz, C. M., Napierala, M., Napierala, J. S. Tags: Neurodegenerative disorders RESEARCH ARTICLE Source Type: research

First person - Anjali Bajpai [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. Anjali Bajpai is first author on ‘A Drosophila model of oral peptide therapeutics for adult intestinal stem cell tumors’, published in DMM. Anjali is a Wellcome Trust DBT India Alliance early-career fellow in the lab of Prof. Pradip Sinha at Indian Institute of Technology, Kanpur, India, investigating the developmental principles that govern carcinogenesis using Drosophila as a model system. (Sour...
Source: DMM Disease Models and Mechanisms - July 23, 2020 Category: Biomedical Science Tags: FIRST PERSON Source Type: research

A Drosophila model of oral peptide therapeutics for adult intestinal stem cell tumors [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 - July 23, 2020 Category: Biomedical Science Authors: Bajpai, A., Quazi, T. A., Tang, H.-W., Manzar, N., Singh, V., Thakur, A., Ateeq, B., Perrimon, N., Sinha, P. Tags: Cancer, Drosophila as a Disease Model RESEARCH ARTICLE Source Type: research

Temporal patterning in neural progenitors: from Drosophila development to childhood cancers [REVIEW]
ABSTRACT The developing central nervous system (CNS) is particularly prone to malignant transformation, but the underlying mechanisms remain unresolved. However, periods of tumor susceptibility appear to correlate with windows of increased proliferation, which are often observed during embryonic and fetal stages and reflect stereotypical changes in the proliferative properties of neural progenitors. The temporal mechanisms underlying these proliferation patterns are still unclear in mammals. In Drosophila, two decades of work have revealed a network of sequentially expressed transcription factors and RNA-binding proteins t...
Source: DMM Disease Models and Mechanisms - July 22, 2020 Category: Biomedical Science Authors: Maurange, C. Tags: Cancer, Developmental Disorders, Drosophila as a Disease Model REVIEW Source Type: research

First person - Lisa Elmen [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. Lisa Elmén is first author on ‘Silencing of CCR4-NOT complex subunits affects heart structure and function’, published in DMM. Lisa conducted the research described in this article while a lab manager/research associate in Rolf Bodmer's lab at Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA. She is now a scientist at Bloom Science, San Diego, CA, USA researching bacter...
Source: DMM Disease Models and Mechanisms - July 20, 2020 Category: Biomedical Science Tags: FIRST PERSON Source Type: research

First person - Nagisa Yoshida [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. Nagisa Yoshida is first author on ‘The zebrafish as a novel model for the in vivo study of Toxoplasma gondii replication and interaction with macrophages’, published in DMM. Nagisa conducted the research described in this article while a PhD student in Prof. Serge Mostowy and Dr Eva Frickel's labs at Imperial College London/The Francis Crick Institute/London School of Hygiene and Tropical Medicine...
Source: DMM Disease Models and Mechanisms - July 20, 2020 Category: Biomedical Science Tags: FIRST PERSON Source Type: research

Silencing of CCR4-NOT complex subunits affects heart structure and function [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 - July 20, 2020 Category: Biomedical Science Authors: Elmen, L., Volpato, C. B., Kervadec, A., Pineda, S., Kalvakuri, S., Alayari, N. N., Foco, L., Pramstaller, P. P., Ocorr, K., Rossini, A., Cammarato, A., Colas, A. R., Hicks, A. A., Bodmer, R. Tags: Stem Cells, Drosophila as a Disease Model RESEARCH ARTICLE Source Type: research

The zebrafish as a novel model for the in vivo study of Toxoplasma gondii replication and interaction with macrophages [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 - July 20, 2020 Category: Biomedical Science Authors: Yoshida, N., Domart, M.-C., Peddie, C. J., Yakimovich, A., Mazon-Moya, M. J., Hawkins, T. A., Collinson, L., Mercer, J., Frickel, E.-M., Mostowy, S. Tags: Zebrafish as a Disease Model RESEARCH ARTICLE Source Type: research

First person - Craig Keenan [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. Craig Keenan is first author on ‘Post-traumatic osteoarthritis development is not modified by postnatal chondrocyte deletion of Ccn2’, published in DMM. Craig conducted the research described in this article while a postdoctoral research associate in Dr Blandine Poulet's lab at the University of Liverpool, Liverpool, UK. He is now a lecturer in vertebrate physiology in the lab of Dr Jason Kirby at...
Source: DMM Disease Models and Mechanisms - July 14, 2020 Category: Biomedical Science Tags: FIRST PERSON Source Type: research

Post-traumatic osteoarthritis development is not modified by postnatal chondrocyte deletion of Ccn2 [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 - July 14, 2020 Category: Biomedical Science Authors: Keenan, C. M., Ramos-Mucci, L., Kanakis, I., Milner, P. I., Leask, A., Abraham, D., Bou-Gharios, G., Poulet, B. Tags: RESEARCH ARTICLE Source Type: research

A mouse SWATH-mass spectrometry reference spectral library enables deconvolution of species-specific proteomic alterations in human tumour xenografts [RESOURCE ARTICLE]
ABSTRACT SWATH-mass spectrometry (MS) enables accurate and reproducible proteomic profiling in multiple model organisms including the mouse. Here, we present a comprehensive mouse reference spectral library (MouseRefSWATH) that permits quantification of up to 10,597 proteins (62.2% of the mouse proteome) by SWATH-MS. We exploit MouseRefSWATH to develop an analytical pipeline for species-specific deconvolution of proteomic alterations in human tumour xenografts (XenoSWATH). This method overcomes the challenge of high sequence similarity between mouse and human proteins, facilitating the study of host microenvironment-tumour...
Source: DMM Disease Models and Mechanisms - July 14, 2020 Category: Biomedical Science Authors: Krasny, L., Bland, P., Burns, J., Lima, N. C., Harrison, P. T., Pacini, L., Elms, M. L., Ning, J., Martinez, V. G., Yu, Y.-R., Acton, S. E., Ho, P.-C., Calvo, F., Swain, A., Howard, B. A., Natrajan, R. C., Huang, P. H. Tags: Cancer, Tools and Resources for Mouse Studies RESOURCE ARTICLE Source Type: research

Sentinel interaction mapping - a generic approach for the functional analysis of human disease gene variants using yeast [RESOURCE ARTICLE]
ABSTRACT Advances in sequencing technology have led to an explosion in the number of known genetic variants of human genes. A major challenge is to now determine which of these variants contribute to diseases as a result of their effect on gene function. Here, we describe a generic approach using the yeast Saccharomyces cerevisiae to quickly develop gene-specific in vivo assays that can be used to quantify the level of function of a genetic variant. Using synthetic dosage lethality screening, ‘sentinel’ yeast strains are identified that are sensitive to overexpression of a human disease gene. Variants of the ge...
Source: DMM Disease Models and Mechanisms - July 8, 2020 Category: Biomedical Science Authors: Young, B. P., Post, K. L., Chao, J. T., Meili, F., Haas, K., Loewen, C. Tags: RESOURCE ARTICLE Source Type: research

Neuromuscular disease modeling on a chip [REVIEW]
ABSTRACT Organs-on-chips are broadly defined as microfabricated surfaces or devices designed to engineer cells into microscale tissues with native-like features and then extract physiologically relevant readouts at scale. Because they are generally compatible with patient-derived cells, these technologies can address many of the human relevance limitations of animal models. As a result, organs-on-chips have emerged as a promising new paradigm for patient-specific disease modeling and drug development. Because neuromuscular diseases span a broad range of rare conditions with diverse etiology and complex pathophysiology, the...
Source: DMM Disease Models and Mechanisms - July 7, 2020 Category: Biomedical Science Authors: Santoso, J. W., McCain, M. L. Tags: Organoids, Neuromuscular, Model Systems in Drug Discovery REVIEW Source Type: research

First person - Dimitrije Stankovic [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. Dimitrije Stanković is first author on ‘A Drosophila model to study retinitis pigmentosa pathology associated with mutations in the core splicing factor Prp8’, published in DMM. Dimitrije is a PhD student in the lab of Mirka Uhlirova at CECAD Research Center in Cologne, Germany, investigating the functional consequences of aberrant pre-mRNA splicing in the context of regulation of gene expression...
Source: DMM Disease Models and Mechanisms - June 26, 2020 Category: Biomedical Science Tags: FIRST PERSON Source Type: research

First person - Alec Nickolls [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. Alec Nickolls is first author on ‘Human embryoid bodies as a 3D tissue model of the extracellular matrix and α-dystroglycanopathies’, published in DMM. Alec conducted the research described in this article while a PhD student in Carsten Bönnemann's lab at National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. He is now a postdoctoral fell...
Source: DMM Disease Models and Mechanisms - June 26, 2020 Category: Biomedical Science Tags: FIRST PERSON Source Type: research

First person - Sara Ibrahim [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. Sara Ibrahim is first author on ‘A novel Cre-enabled tetracycline-inducible transgenic system for tissue-specific cytokine expression in the zebrafish: CETI-PIC3’, published in DMM. Sara is an MD-PhD student in the lab of Emily K. Sims and Ryan M. Anderson at Indiana University School of Medicine, Indianapolis, IN, USA, developing and utilizing molecular biology techniques to study β cell dys...
Source: DMM Disease Models and Mechanisms - June 26, 2020 Category: Biomedical Science Tags: FIRST PERSON Source Type: research

Quantitative single-cell interactomes in normal and virus-infected mouse lungs [RESOURCE ARTICLE]
ABSTRACT Mammalian organs consist of diverse, intermixed cell types that signal to each other via ligand-receptor interactions – an interactome – to ensure development, homeostasis and injury-repair. Dissecting such intercellular interactions is facilitated by rapidly growing single-cell RNA sequencing (scRNA-seq) data; however, existing computational methods are often not readily adaptable by bench scientists without advanced programming skills. Here, we describe a quantitative intuitive algorithm, coupled with an optimized experimental protocol, to construct and compare interactomes in control and Sendai viru...
Source: DMM Disease Models and Mechanisms - June 26, 2020 Category: Biomedical Science Authors: Cain, M. P., Hernandez, B. J., Chen, J. Tags: RESOURCE ARTICLE Source Type: research

A Drosophila model to study retinitis pigmentosa pathology associated with mutations in the core splicing factor Prp8 [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 26, 2020 Category: Biomedical Science Authors: Stankovic, D., Claudius, A.-K., Schertel, T., Bresser, T., Uhlirova, M. Tags: Drosophila as a Disease Model RESEARCH ARTICLE Source Type: research

Human embryoid bodies as a 3D tissue model of the extracellular matrix and {alpha}-dystroglycanopathies [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 26, 2020 Category: Biomedical Science Authors: Nickolls, A. R., Lee, M. M., Zukosky, K., Mallon, B. S., Bönnemann, C. G. Tags: Organoids, Neuromuscular RESOURCE ARTICLE Source Type: research

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 26, 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 24, 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 24, 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 24, 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 23, 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 17, 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 15, 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 15, 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 15, 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 3, 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 3, 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 3, 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 - June 1, 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 Sprin...
Source: DMM Disease Models and Mechanisms - May 29, 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 29, 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

Building bridges, not walls: spinal cord regeneration in zebrafish [REVIEW]
ABSTRACT Spinal cord injury is a devastating condition in which massive cell death and disruption of neural circuitry lead to long-term chronic functional impairment and paralysis. In mammals, spinal cord tissue has minimal capacity to regenerate after injury. In stark contrast, the regeneration of a completely transected spinal cord and accompanying reversal of paralysis in adult zebrafish is arguably one of the most spectacular biological phenomena in nature. Here, we review reports from the last decade that dissect the mechanisms of spinal cord regeneration in zebrafish. We highlight recent progress as well as areas req...
Source: DMM Disease Models and Mechanisms - May 27, 2020 Category: Biomedical Science Authors: Cigliola, V., Becker, C. J., Poss, K. D. Tags: Zebrafish as a Disease Model REVIEW Source Type: research

Activated pathogenic Th17 lymphocytes induce hypertension following high-fructose intake in Dahl salt-sensitive but not Dahl salt-resistant rats [RESEARCH ARTICLE]
ABSTRACT High-salt intake and high-fructose intake are risk factors for hypertension via oxidative stress and inflammation. T helper (Th)17 lymphocytes play an important role in the development of hypertension. Here, we tested the hypothesis that activation of pathogenic Th17 lymphocytes induces hypertension after high-fructose intake in Dahl salt-sensitive (SS) but not Dahl salt-resistant (SR) rats. Eight-week-old male SS and SR rats were offered 20% fructose solution or tap water only for 4 weeks. Systolic blood pressure was measured by the tail-cuff method. T lymphocyte [Th17 and T regulatory (Treg)] profiling was ...
Source: DMM Disease Models and Mechanisms - May 27, 2020 Category: Biomedical Science Authors: Lee, E., Kim, N., Kang, J., Yoon, S., Lee, H.-A., Jung, H., Kim, S.-H., Kim, I. Tags: Rat as a Disease Model RESEARCH ARTICLE Source Type: research

First person - Anna Gray [FIRST PERSON]
ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms (DMM), helping early-career researchers promote themselves alongside their papers. Anna Gray is first author on ‘ Deterioration of muscle force and contractile characteristics are early pathological events in spinal and bulbar muscular atrophy mice’, published in DMM. Anna conducted the research described in this article while a PhD student in Prof. Linda Greensmith's lab at the Department of Neuromuscular Disease, UCL Institute of Neurology, Queen Square, London, UK. She ...
Source: DMM Disease Models and Mechanisms - May 26, 2020 Category: Biomedical Science Tags: FIRST PERSON Source Type: research

First person - Kristin Ates [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. Kristin Ates is first author on ‘ Deficiency in the endocytic adaptor proteins PHETA1/2 impairs renal and craniofacial development’, published in DMM. Kristin is an MD/PhD student in the lab of Y. Albert Pan at Augusta University, Augusta, GA, USA, investigating the underlying pathogenesis of endosomal and lysosomal diseases. (Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - May 26, 2020 Category: Biomedical Science Tags: FIRST PERSON Source Type: research

Modeling human epigenetic disorders in mice: Beckwith-Wiedemann syndrome and Silver-Russell syndrome [REVIEW]
ABSTRACT Genomic imprinting, a phenomenon in which the two parental alleles are regulated differently, is observed in mammals, marsupials and a few other species, including seed-bearing plants. Dysregulation of genomic imprinting can cause developmental disorders such as Beckwith-Wiedemann syndrome (BWS) and Silver-Russell syndrome (SRS). In this Review, we discuss (1) how various (epi)genetic lesions lead to the dysregulation of clinically relevant imprinted loci, and (2) how such perturbations may contribute to the developmental defects in BWS and SRS. Given that the regulatory mechanisms of most imprinted clusters are w...
Source: DMM Disease Models and Mechanisms - May 26, 2020 Category: Biomedical Science Authors: Chang, S., Bartolomei, M. S. Tags: REVIEW Source Type: research

Deterioration of muscle force and contractile characteristics are early pathological events in spinal and bulbar muscular atrophy mice [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 26, 2020 Category: Biomedical Science Authors: Gray, A. L., Annan, L., Dick, J. R. T., La Spada, A. R., Hanna, M. G., Greensmith, L., Malik, B. Tags: Neuromuscular RESEARCH ARTICLE Source Type: research

Deficiency in the endocytic adaptor proteins PHETA1/2 impairs renal and craniofacial development [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 26, 2020 Category: Biomedical Science Authors: Ates, K. M., Wang, T., Moreland, T., Veeranan-Karmegam, R., Ma, M., Jeter, C., Anand, P., Wenzel, W., Kim, H.-G., Wolfe, L. A., Stephen, J., Adams, D. R., Markello, T., Tifft, C. J., Settlage, R., Gahl, W. A., Gonsalvez, G. B., Malicdan, M. C., Flanagan-S Tags: Zebrafish as a Disease Model RESEARCH ARTICLE Source Type: research

Temperature-sensitive spinal muscular atrophy-causing point mutations lead to SMN instability, locomotor defects and premature lethality in Drosophila [RESEARCH ARTICLE]
ABSTRACT Spinal muscular atrophy (SMA) is the leading genetic cause of death in young children, arising from homozygous deletion or mutation of the survival motor neuron 1 (SMN1) gene. SMN protein expressed from a paralogous gene, SMN2, is the primary genetic modifier of SMA; small changes in overall SMN levels cause dramatic changes in disease severity. Thus, deeper insight into mechanisms that regulate SMN protein stability should lead to better therapeutic outcomes. Here, we show that SMA patient-derived missense mutations in the Drosophila SMN Tudor domain exhibit a pronounced temperature sensitivity that affects organ...
Source: DMM Disease Models and Mechanisms - May 22, 2020 Category: Biomedical Science Authors: Raimer, A. C., Singh, S. S., Edula, M. R., Paris-Davila, T., Vandadi, V., Spring, A. M., Matera, A. G. Tags: Neuromuscular, Drosophila as a Disease Model RESEARCH ARTICLE Source Type: research

Diverse dystonin gene mutations cause distinct patterns of Dst isoform deficiency and phenotypic heterogeneity in Dystonia musculorum mice [RESEARCH ARTICLE]
ABSTRACT Loss-of-function mutations in dystonin (DST) can cause hereditary sensory and autonomic neuropathy type 6 (HSAN-VI) or epidermolysis bullosa simplex (EBS). Recently, DST-related diseases were recognized to be more complex than previously thought because a patient exhibited both neurological and skin manifestations, whereas others display only one or the other. A single DST locus produces at least three major DST isoforms: DST-a (neuronal isoform), DST-b (muscular isoform) and DST-e (epithelial isoform). Dystonia musculorum (dt) mice, which have mutations in Dst, were originally identified as spontaneous mutants di...
Source: DMM Disease Models and Mechanisms - May 21, 2020 Category: Biomedical Science Authors: Yoshioka, N., Kabata, Y., Kuriyama, M., Bizen, N., Zhou, L., Tran, D. M., Yano, M., Yoshiki, A., Ushiki, T., Sproule, T. J., Abe, R., Takebayashi, H. Tags: Neuromuscular RESEARCH ARTICLE Source Type: research