Read by QxMD icon Read

Zebrafish disease modelling

Voon Kin Chin, Tze Yan Lee, Basir Rusliza, Pei Pei Chong
Candida bloodstream infections remain the most frequent life-threatening fungal disease, with Candida albicans accounting for 70% to 80% of the Candida isolates recovered from infected patients. In nature, Candida species are part of the normal commensal flora in mammalian hosts. However, they can transform into pathogens once the host immune system is weakened or breached. More recently, mortality attributed to Candida infections has continued to increase due to both inherent and acquired drug resistance in Candida, the inefficacy of the available antifungal drugs, tedious diagnostic procedures, and a rising number of immunocompromised patients...
October 18, 2016: International Journal of Molecular Sciences
Chien-Wei Feng, Han-Chun Hung, Shi-Ying Huang, Chun-Hong Chen, Yun-Ru Chen, Chun-Yu Chen, San-Nan Yang, Hui-Min David Wang, Ping-Jyun Sung, Jyh-Horng Sheu, Kuan-Hao Tsui, Wu-Fu Chen, Zhi-Hong Wen
Parkinson's disease (PD) is a neurodegenerative disorder characterized by tremor, rigidity, bradykinesia, and gait impairment. In a previous study, we found that the marine-derived compound 11-dehydrosinulariolide (11-de) upregulates the Akt/PI3K pathway to protect cells against 6-hydroxydopamine (6-OHDA)-mediated damage. In the present study, SH-SY5Y, zebrafish and rats were used to examine the therapeutic effect of 11-de. The results revealed the mechanism by which 11-de exerts its therapeutic effect: the compound increases cytosolic or mitochondrial DJ-1 expression, and then activates the downstream Akt/PI3K, p-CREB, and Nrf2/HO-1 pathways...
October 17, 2016: Marine Drugs
Carl Nathan
In tuberculosis, some macrophages in granulomas assume an epitheloid appearance. Using the Mycobacterium marinum-zebrafish model, Cronan et al. (2016) now show that granuloma macrophages undergo reprograming events involving E-cadherin-dependent formation of epithelial-like cell-cell junctions. Interference with the function of E-cadherin in macrophages disorganized the granulomas and protected the fish, introducing new ideas and questions about macrophage function and granulomatous diseases.
October 18, 2016: Immunity
Xunian Zhou, Grace Gar-Lee Yue, Minghua Liu, Zhili Zuo, Julia Kin-Ming Lee, Mingyue Li, Stephen Kwok-Wing Tsui, Kwok-Pui Fung, Handong Sun, Jianxin Pu, Clara Bik-San Lau
Eriocalyxin B (EriB), a natural ent-kaurane diterpenoid isolated from the plant Isodon eriocalyx var. laxiflora, has emerged as a promising anticancer agent. The effects of EriB on angiogenesis were explored in the present study. Here we demonstrated that the subintestinal vein formation was significantly inhibited by EriB treatment (10, 15 μM) in zebrafish embryos, which was resulted from the alteration of various angiogenic genes as shown in transcriptome profiling. In human umbilical vein endothelial cells, EriB treatment (50, 100 nM) could significantly block vascular endothelial growth factors (VEGF)-induced cell proliferation, tube formation, cell migration and cell invasion...
October 14, 2016: Oncotarget
Gina L O'Grady, Heather A Best, Tamar E Sztal, Vanessa Schartner, Myriam Sanjuan-Vazquez, Sandra Donkervoort, Osorio Abath Neto, Roger Bryan Sutton, Biljana Ilkovski, Norma Beatriz Romero, Tanya Stojkovic, Jahannaz Dastgir, Leigh B Waddell, Anne Boland, Ying Hu, Caitlin Williams, Avnika A Ruparelia, Thierry Maisonobe, Anthony J Peduto, Stephen W Reddel, Monkol Lek, Taru Tukiainen, Beryl B Cummings, Himanshu Joshi, Juliette Nectoux, Susan Brammah, Jean-François Deleuze, Viola Oorschot Ing, Georg Ramm, Didem Ardicli, Kristen J Nowak, Beril Talim, Haluk Topaloglu, Nigel G Laing, Kathryn N North, Daniel G MacArthur, Sylvie Friant, Nigel F Clarke, Robert J Bryson-Richardson, Carsten G Bönnemann, Jocelyn Laporte, Sandra T Cooper
This study establishes PYROXD1 variants as a cause of early-onset myopathy and uses biospecimens and cell lines, yeast, and zebrafish models to elucidate the fundamental role of PYROXD1 in skeletal muscle. Exome sequencing identified recessive variants in PYROXD1 in nine probands from five families. Affected individuals presented in infancy or childhood with slowly progressive proximal and distal weakness, facial weakness, nasal speech, swallowing difficulties, and normal to moderately elevated creatine kinase...
September 28, 2016: American Journal of Human Genetics
Tongkai Chen, Chuwen Li, Ye Li, Yi Xiang, Simon Ming Yuen Lee, Ying Zheng
Schisantherin A (SA) is a promising anti-Parkinsonism Chinese herbal medicine but with poor water solubility and challenges to be delivered to the brain. We formulated SA as nanocrystals (SA-NC), aiming to improve its solubility, pharmacokinetic profile and thus provide a potential therapeutic agent for the treatment of Parkinson's disease (PD). The rod-shaped SA-NC had a particle size of ~160 nm with 33.3% drug loading, and the nanocrystals exhibited a fast dissolution rate in vitro. The intact drug nanocrystals could be internalized into Madin-Darby canine kidney (MDCK) cells, which were followed by rapid intracellular release, and most of the drug was transported to the basolateral side in its soluble form...
October 14, 2016: Molecular Pharmaceutics
Ann Williams, Ian M Orme
This article provides an overview of the animal models currently used in tuberculosis research, both for understanding the basic science of the disease process and also for practical issues such as testing new vaccine candidates and evaluating the activity of potential new drugs. Animals range in size, from zebrafish to cattle, and in degrees of similarity to the human disease from both an immunological and pathologic perspective. These models have provided a great wealth of information (impossible to obtain simply from observing infected humans), but we emphasize here that one must use care in interpreting or applying this information, and indeed the true art of animal modeling is in deciding what is pertinent information and what might not be...
August 2016: Microbiology Spectrum
Akira Hanashima, Ken Hashimoto, Yoshihiro Ujihara, Takeshi Honda, Tomoko Yobimoto, Aya Kodama, Satoshi Mohri
Connectin, also called titin, is the largest protein with a critical function as a molecular spring during contraction and relaxation of striated muscle; its mutation leads to severe myopathy and cardiomyopathy. To uncover the cause of this pathogenesis, zebrafish have recently been used as disease models because they are easier to genetically modify than mice. Although the gene structures and putative primary structures of zebrafish connectin have been determined, the actual primary structures of zebrafish connectin in heart and skeletal muscles remain unclear because of its large size and the PCR amplification-associated difficulties...
October 7, 2016: Gene
Charles H Williams, Charles C Hong
Target based chemical screens are a mainstay of modern drug discovery, but the effectiveness of this reductionist approach is being questioned in light of declines in pharmaceutical R & D efficiency. In recent years, phenotypic screens have gained increasing acceptance as a complementary/alternative approach to early drug discovery. We discuss the various model organisms used in phenotypic screens, with particular focus on zebrafish, which has emerged as a leading model of in vivo phenotypic screens. Additionally, we anticipate therapeutic opportunities, particularly in orphan disease space, in the context of rapid advances in human Mendelian genetics, electronic health record (EHR)-enabled genome-phenome associations, and genome editing...
2016: Computational and Structural Biotechnology Journal
Mauro S Porcel de Peralta, Valeria S Mouguelar, María Antonella Sdrigotti, Felipe A A Ishiy, Roberto D Fanganiello, Maria R Passos-Bueno, Gabriela Coux, Nora B Calcaterra
Treacher Collins Syndrome (TCS) is a rare congenital disease (1:50 000 live births) characterized by craniofacial defects, including hypoplasia of facial bones, cleft palate and palpebral fissures. Over 90% of the cases are due to mutations in the TCOF1 gene, which codifies the nucleolar protein Treacle. Here we report a novel TCS-like zebrafish model displaying features that fully recapitulate the spectrum of craniofacial abnormalities observed in patients. As it was reported for a Tcof1(+/-) mouse model, Treacle depletion in zebrafish caused reduced rRNA transcription, stabilization of Tp53 and increased cell death in the cephalic region...
October 6, 2016: Cell Death & Disease
Christopher J Sifuentes, Jung-Woong Kim, Anand Swaroop, Pamela A Raymond
Purpose: Zebrafish neurons regenerate from Müller glia following retinal lesions. Genes and signaling pathways important for retinal regeneration in zebrafish have been described, but our understanding of how Müller glial stem cell properties are regulated is incomplete. Mammalian Müller glia possess a latent neurogenic capacity that might be enhanced in regenerative therapies to treat degenerative retinal diseases. Methods: To identify transcriptional changes associated with stem cell properties in zebrafish Müller glia, we performed a comparative transcriptome analysis from isolated cells at 8 and 16 hours following an acute photic lesion, prior to the asymmetric division that produces retinal progenitors...
October 1, 2016: Investigative Ophthalmology & Visual Science
Rachael A Powis, Evangelia Karyka, Penelope Boyd, Julien Côme, Ross A Jones, Yinan Zheng, Eva Szunyogova, Ewout J N Groen, Gillian Hunter, Derek Thomson, Thomas M Wishart, Catherina G Becker, Simon H Parson, Cécile Martinat, Mimoun Azzouz, Thomas H Gillingwater
The autosomal recessive neuromuscular disease spinal muscular atrophy (SMA) is caused by loss of survival motor neuron (SMN) protein. Molecular pathways that are disrupted downstream of SMN therefore represent potentially attractive therapeutic targets for SMA. Here, we demonstrate that therapeutic targeting of ubiquitin pathways disrupted as a consequence of SMN depletion, by increasing levels of one key ubiquitination enzyme (ubiquitin-like modifier activating enzyme 1 [UBA1]), represents a viable approach for treating SMA...
July 21, 2016: JCI Insight
Marta Carnovali, Livio Luzi, Giuseppe Banfi, Massimo Mariotti
Type II diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia that induce other pathologies including diabetic retinopathy and bone disease. The mechanisms implicated in bone alterations induced by type II diabetes mellitus have been debated for years and are not yet clear because there are other factors involved that hide bone mineral density alterations. Despite this, it is well known that chronic hyperglycemia affects bone health causing fragility, mechanical strength reduction and increased propensity of fractures because of impaired bone matrix microstructure and aberrant bone cells function...
October 1, 2016: Endocrine
Meriam Boubakri, Taro Chaya, Hiromi Hirata, Naoko Kajimura, Ryusuke Kuwahara, Akiko Ueno, Jarema Malicki, Takahisa Furukawa, Yoshihiro Omori
In the retina, aberrant opsin transport from cell bodies to outer segments leads to retinal degenerative diseases such as retinitis pigmentosa. Opsin transport is facilitated by the intraflagellar transport (IFT) system which mediates the bidirectional movement of proteins within cilia. In contrast to functions of the anterograde transport executed by IFT complex B (IFT-B), the precise functions of the retrograde transport mediated by IFT complex A (IFT-A) have not been well studied in photoreceptor cilia. Here, we analyzed developing zebrafish larvae carrying a null mutation in ift122 encoding a component of IFT-A...
September 28, 2016: Journal of Biological Chemistry
Federico Sicca, Elena Ambrosini, Maria Marchese, Luigi Sforna, Ilenio Servettini, Giulia Valvo, Maria Stefania Brignone, Angela Lanciotti, Francesca Moro, Alessandro Grottesi, Luigi Catacuzzeno, Sara Baldini, Sonia Hasan, Maria Cristina D'Adamo, Fabio Franciolini, Paola Molinari, Filippo M Santorelli, Mauro Pessia
Dysfunction of the inwardly-rectifying potassium channels Kir4.1 (KCNJ10) represents a pathogenic mechanism contributing to Autism-Epilepsy comorbidity. To define the role of Kir4.1 variants in the disorder, we sequenced KCNJ10 in a sample of affected individuals, and performed genotype-phenotype correlations. The effects of mutations on channel activity, protein trafficking, and astrocyte function were investigated in Xenopus laevis oocytes, and in human astrocytoma cell lines. An in vivo model of the disorder was also explored through generation of kcnj10a morphant zebrafish overexpressing the mutated human KCNJ10...
September 28, 2016: Scientific Reports
Krzysztof Jagla, Benoit Kalman, Thomas Boudou, Sylvie Hénon, Sabrina Batonnet-Pichon
The use of the adapted models to decipher patho-physiological mechanisms of human diseases is always a great challenge. This is of particular importance for early-onset myopathies, in which pathological mutations often impact not only on muscle structure and function but also on developmental processes. Mice are currently the main animal model used to study neuromuscular disorders including the early-onset myopathies. However strategies based on simple animal models and on transdisciplinary approaches exploring mechanical muscle cell properties emerge as attractive, non-exclusive alternatives...
September 23, 2016: Seminars in Cell & Developmental Biology
Victoria McCutcheon, Eugene Park, Elaine Liu, Pooya Sobhe Bidari, Jahan Tavakkoli, Xiao-Yan Wen, Andrew J Baker
Traumatic brain injury (TBI) is a leading cause of death and morbidity in industrialized countries with considerable associated healthcare costs. The cost and time associated with preclinical development of TBI therapeutics is lengthy and expensive with a poor track record of successful translation to the clinic. The zebrafish is an emerging model organism in research with unique technical and genomic strengths in the study of disease and development. Its high degree of genetic homology and cell signaling pathways relative to mammalian species and amenability to high and medium throughput assays has potential to accelerate the rate of therapeutic drug identification...
September 20, 2016: Journal of Neurotrauma
Edward Málaga-Trillo, Katharina Ochs
Prions and Amyloid beta (Aβ) peptides induce synaptic damage via complex mechanisms that include the pathological alteration of intracellular signaling cascades. The host-encoded cellular prion protein (PrP(C)) acts as a high-affinity cell surface receptor for both toxic species and it can modulate the endocytic trafficking of the N-methyl D-aspartate (NMDA) receptor and E-cadherin adhesive complexes via Src family kinases (SFKs). Interestingly, SFK-mediated control of endocytosis is a widespread mechanism used to regulate the activity of important transmembrane proteins, including neuroreceptors for major excitatory and inhibitory neurotransmitters...
September 20, 2016: Prion
Dong-Yang Guo, Chao Cao, Xiao-Yu Zhang, Li-Xin Xiang, Jian-Zhong Shao
Scavenger receptor class A member 5 (SCARA5) and high-mobility group box 1 (HMGB1) protein have become increasingly attractive for their critical functions in innate inflammatory reactions and disorders. However, the functional relevance between these two molecules has never been described. This study discovered that SCARA5 is an HMGB1 recognition receptor that is negatively involved in HMGB1-mediated inflammation in pufferfish (Tetraodon nigroviridis) and zebrafish (Danio rerio) models. Hence, SCARA5 is added as a new member to the HMGB1 receptor family...
September 19, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Yonghe Ding, Pamela A Long, J Martijn Bos, Yu-Huan Shih, Xiao Ma, Rhianna S Sundsbak, Jianhua Chen, Yiwen Jiang, Liqun Zhao, Xinyang Hu, Jianan Wang, Yongyong Shi, Michael J Ackerman, Xueying Lin, Stephen C Ekker, Margaret M Redfield, Timothy M Olson, Xiaolei Xu
Mutagenesis screening is a powerful forward genetic approach that has been successfully applied in lower-model organisms to discover genetic factors for biological processes. This phenotype-based approach has yet to be established in vertebrates for probing major human diseases, largely because of the complexity of colony management. Herein, we report a rapid strategy for identifying genetic modifiers of cardiomyopathy (CM). Based on the application of doxorubicin stress to zebrafish insertional cardiac (ZIC) mutants, we identified 4 candidate CM-modifying genes, of which 3 have been linked previously to CM...
September 8, 2016: JCI Insight
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"