Deep learning enables automated volumetric assessments of cardiac function in zebrafish [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 - October 24, 2019 Category: Biomedical Science Authors: Akerberg, A. A., Burns, C. E., Burns, C. G., Nguyen, C. Tags: Zebrafish as a Disease Model RESOURCE ARTICLE Source Type: research
Translational medicine in neuromuscular disorders: from academia to industry [SPECIAL ARTICLE]
This article discusses the advantages and challenges for translational research initiated from academia, and the trend towards bridging the gap between discovery and translation to the clinic. A focus is made on recent advances in therapeutic development for neuromuscular disorders. (Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - October 23, 2019 Category: Biomedical Science Authors: Cowling, B. S., Thielemans, L. Tags: Neuromuscular SPECIAL ARTICLE Source Type: research
First person - Jocelyn Wessels [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. Jocelyn Wessels is first author on ‘Medroxyprogesterone acetate alters the vaginal microbiota and microenvironment in women and increases susceptibility to HIV-1 in humanized mice’, published in DMM. Jocelyn conducted the research described in this article while a Postdoctoral Fellow in Dr Charu Kaushic's lab at McMaster University, Hamilton, Canada. She is now a Postdoctoral Fellow in the l...
Source: DMM Disease Models and Mechanisms - October 22, 2019 Category: Biomedical Science Tags: FIRST PERSON Source Type: research
Medroxyprogesterone acetate alters the vaginal microbiota and microenvironment in women and increases susceptibility to HIV-1 in humanized 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 - October 22, 2019 Category: Biomedical Science Authors: Wessels, J. M., Lajoie, J., Cooper, M. I. J. H., Omollo, K., Felker, A. M., Vitali, D., Dupont, H. A., Nguyen, P. V., Mueller, K., Vahedi, F., Kimani, J., Oyugi, J., Cheruiyot, J., Mungai, J. N., Deshiere, A., Tremblay, M. J., Mazzulli, T., Stearns, J. C. Tags: Microbiome RESEARCH ARTICLE Source Type: research
Fetal exposure to maternal inflammation interrupts murine intestinal development and increases susceptibility to neonatal intestinal injury [RESEARCH ARTICLE]
ABSTRACT
Fetal exposure to chorioamnionitis can impact the outcomes of the developing fetus both at the time of birth and in the subsequent neonatal period. Infants exposed to chorioamnionitis have a higher incidence of gastrointestinal (GI) pathology, including necrotizing enterocolitis (NEC); however, the mechanism remains undefined. To simulate the fetal exposure to maternal inflammation (FEMI) induced by chorioamnionitis, pregnant mice (C57BL/6J, IL-6–/–, RAG–/– or TNFR1–/–) were injected intraperitoneally on embryonic day (E)15.5 with lipopolysaccharide (LPS; 100 µg/kg bo...
Source: DMM Disease Models and Mechanisms - October 20, 2019 Category: Biomedical Science Authors: Elgin, T. G., Fricke, E. M., Gong, H., Reese, J., Mills, D. A., Kalantera, K. M., Underwood, M. A., McElroy, S. J. Tags: RESEARCH ARTICLE Source Type: research
Reversion of tumor hepatocytes to normal hepatocytes during liver tumor regression in an oncogene-expressing transgenic zebrafish model [RESEARCH ARTICLE]
ABSTRACT
Tumors are frequently dependent on primary oncogenes to maintain their malignant properties (known as ‘oncogene addiction’). We have previously established several inducible hepatocellular carcinoma (HCC) models in zebrafish by transgenic expression of an oncogene. These tumor models are strongly oncogene addicted, as the induced and histologically proven liver tumors regress after suppression of oncogene expression by removal of a chemical inducer. However, the question of whether the liver tumor cells are eliminated or revert to normal cells remains unanswered. In the present study, we generated a no...
Source: DMM Disease Models and Mechanisms - October 16, 2019 Category: Biomedical Science Authors: Li, Y., Agrawal, I., Gong, Z. Tags: Cancer, Zebrafish as a Disease Model RESEARCH ARTICLE Source Type: research
Inducible SMARCAL1 knockdown in iPSC reveals a link between replication stress and altered expression of master differentiation genes [RESEARCH ARTICLE]
In conclusion, our conditional SMARCAL1 knockdown model in iPSCs may represent a powerful model when studying pathogenetic mechanisms of severe Schimke immuno-osseous dysplasia. (Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - October 16, 2019 Category: Biomedical Science Authors: Pugliese, G. M., Salaris, F., Palermo, V., Marabitti, V., Morina, N., Rosa, A., Franchitto, A., Pichierri, P. Tags: Stem Cells, Rare diseases RESEARCH ARTICLE Source Type: research
CRISPR/Cas9-mediated genome editing in nonhuman primates [REVIEW]
ABSTRACT
Owing to their high similarity to humans, non-human primates (NHPs) provide an exceedingly suitable model for the study of human disease. In this Review, we summarize the history of transgenic NHP models and the progress of CRISPR/Cas9-mediated genome editing in NHPs, from the first proof-of-principle green fluorescent protein-expressing monkeys to sophisticated NHP models of human neurodegenerative disease that accurately phenocopy several complex disease features. We discuss not only the breakthroughs and advantages, but also the potential shortcomings of the application of the CRISPR/Cas9 system to NHPs that ha...
Source: DMM Disease Models and Mechanisms - October 15, 2019 Category: Biomedical Science Authors: Kang, Y., Chu, C., Wang, F., Niu, Y. Tags: REVIEW Source Type: research
mTOR hyperactivity mediates lysosomal dysfunction in Gaucher's disease iPSC-neuronal cells [RESEARCH ARTICLE]
ABSTRACT
Bi-allelic GBA1 mutations cause Gaucher's disease (GD), the most common lysosomal storage disorder. Neuronopathic manifestations in GD include neurodegeneration, which can be severe and rapidly progressive. GBA1 mutations are also the most frequent genetic risk factors for Parkinson's disease. Dysfunction of the autophagy-lysosomal pathway represents a key pathogenic event in GBA1-associated neurodegeneration. Using an induced pluripotent stem cell (iPSC) model of GD, we previously demonstrated that lysosomal alterations in GD neurons are linked to dysfunction of the transcription factor EB (TFEB). TFEB controls t...
Source: DMM Disease Models and Mechanisms - October 15, 2019 Category: Biomedical Science Authors: Brown, R. A., Voit, A., Srikanth, M. P., Thayer, J. A., Kingsbury, T. J., Jacobson, M. A., Lipinski, M. M., Feldman, R. A., Awad, O. Tags: Stem Cells, Rare diseases RESEARCH ARTICLE Source Type: research
A small bioactive glycoside inhibits epsilon toxin and prevents cell death [RESEARCH ARTICLE]
ABSTRACT
Clostridium perfringens epsilon toxin (Etx) is categorized as the third most lethal bioterrorism agent by the Centers for Disease Control and Prevention (CDC), with no therapeutic counter measures available for humans. Here, we have developed a high-affinity inhibitory compound by synthesizing and evaluating the structure activity relationship (SAR) of a library of diverse glycosides (numbered 1-12). SAR of glycoside-Etx heptamers revealed exceptionally strong H-bond interactions of glycoside-4 with a druggable pocket in the oligomerization and β-hairpin region of Etx. Analysis of its structure suggested that...
Source: DMM Disease Models and Mechanisms - October 9, 2019 Category: Biomedical Science Authors: Shivappagowdar, A., Pati, S., Narayana, C., Ayana, R., Kaushik, H., Sah, R., Garg, S., Khanna, A., Kumari, J., Garg, L., Sagar, R., Singh, S. Tags: RESEARCH ARTICLE Source Type: research
Spz/Toll-6 signal guides organotropic metastasis in Drosophila [RESEARCH ARTICLE]
ABSTRACT
Targeted cell migration plays important roles in developmental biology and disease processes, including in metastasis. Drosophila tumors exhibit traits characteristic of human cancers, providing a powerful model to study developmental and cancer biology. We now find that cells derived from Drosophila eye-disc tumors also display organ-specific metastasis, invading receptive organs but not wing disc. Toll receptors are known to affect innate immunity and the tumor inflammatory microenvironment by modulating the NF-B pathway. Our RNA interference (RNAi) screen and genetic analyses show that Toll-6 is required for mi...
Source: DMM Disease Models and Mechanisms - October 6, 2019 Category: Biomedical Science Authors: Mishra-Gorur, K., Li, D., Ma, X., Yarman, Y., Xue, L., Xu, T. Tags: Drosophila as a Disease Model RESEARCH ARTICLE Source Type: research
Perturbed development of cranial neural crest cells in association with reduced sonic hedgehog signaling underlies the pathogenesis of retinoic-acid-induced cleft palate [RESEARCH ARTICLE]
ABSTRACT
Cleft palate (CP) is one of the most common congenital craniofacial anomalies in humans and can be caused by either single or multiple genetic and environmental factor(s). With respect to environmental factors, excessive intake of vitamin A during early pregnancy is associated with increased incidence of CP in offspring both in humans and in animal models. Vitamin A is metabolized to retinoic acid (RA); however, the pathogenetic mechanism of CP caused by altered RA signaling during early embryogenesis is not fully understood. To investigate the detailed cellular and molecular mechanism of RA-induced CP, we adminis...
Source: DMM Disease Models and Mechanisms - October 3, 2019 Category: Biomedical Science Authors: Wang, Q., Kurosaka, H., Kikuchi, M., Nakaya, A., Trainor, P. A., Yamashiro, T. Tags: RESEARCH ARTICLE Source Type: research
The use of genetically humanized animal models for personalized medicine approaches [SPECIAL ARTICLE]
ABSTRACT
For many genetic diseases, researchers are developing personalized medicine approaches. These sometimes employ custom genetic interventions such as antisense-mediated exon skipping or genome editing, aiming to restore protein function in a mutation-specific manner. Animal models can facilitate the development of personalized medicine approaches; however, given that they target human mutations and therefore human genetic sequences, scientists rely on the availability of humanized animal models. Here, we outline the usefulness, caveats and potential of such models, using the example of the hDMDdel52/mdx model, a hum...
Source: DMM Disease Models and Mechanisms - September 30, 2019 Category: Biomedical Science Authors: Aartsma-Rus, A., van Putten, M. Tags: Neuromuscular SPECIAL ARTICLE Source Type: research
Haploinsufficiency of mechanistic target of rapamycin ameliorates bag3 cardiomyopathy in adult zebrafish [RESEARCH ARTICLE]
This study established the bag3e2/e2 mutant as a DCM model in adult zebrafish and suggested mtor as a candidate therapeutic target gene for BAG3 cardiomyopathy. (Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - September 30, 2019 Category: Biomedical Science Authors: Ding, Y., Dvornikov, A. V., Ma, X., Zhang, H., Wang, Y., Lowerison, M., Packard, R. R., Wang, L., Chen, J., Zhang, Y., Hsiai, T., Lin, X., Xu, X. Tags: Zebrafish as a Disease Model RESEARCH ARTICLE Source Type: research
Drosophila melanogaster: a simple system for understanding complexity [EDITORIAL]
ABSTRACT
Understanding human gene function is fundamental to understanding and treating diseases. Research using the model organism Drosophila melanogaster benefits from a wealth of molecular genetic resources and information useful for efficient in vivo experimentation. Moreover, Drosophila offers a balance as a relatively simple organism that nonetheless exhibits complex multicellular activities. Recent examples demonstrate the power and continued promise of Drosophila research to further our understanding of conserved gene functions. (Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - September 26, 2019 Category: Biomedical Science Authors: Mohr, S. E., Perrimon, N. Tags: Editorials, ASHG, Drosophila as a Disease Model Source Type: research
