scholarly journals ELAC2/RNaseZ linked cardiac hypertrophy in Drosophila melanogaster

2021 ◽  
Author(s):  
Ekaterina Migunova ◽  
Joanna Theophilopoulos ◽  
Marisa Mercadante ◽  
Jing Men ◽  
Chao Zhou ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Human Gene ◽  
Cardiac Contractility ◽  
Model Organism ◽  
Gene Mutations ◽  
Severe Form ◽  
Causal Connection ◽  
Biological Functions ◽  
Rare Form ◽  
Transgenic Lines

A severe form of infantile cardiomyopathy (CM) has been linked to ELAC2 gene mutations. ELAC2 is a highly conserved human gene. It encodes RNaseZL endoribonuclease that plays an essential role in the production of mature tRNAs. To establish a causal connection between ELAC2 variants and CM, here we use a model organism Drosophila melanogaster, which carries ELAC2 homolog - dRNaseZ. Even though dRNaseZ and ELAC2 have diverged in some of their biological functions, our study demonstrates the utility of the fly model to study the mechanism of ELAC2 related pathology. We established transgenic lines harboring dRNaseZ with CM-linked mutations in the background of endogenous dRNaseZ knockout. Importantly, we found that the phenotype of these flies is consistent with pathological features in human patients. Specifically, expression of CM-linked variants in flies causes heart hypertrophy and leads to reduction in cardiac contractility associated with a rare form of CM. This study provides first experimental evidence for the pathogenicity of CM-causing mutations in the ELAC2 protein and lay the foundation to improve our understanding and diagnosis of this rare infantile disease.

scholarly journals Prediction and enrichment analyses of the Homo sapiens−Drosophila melanogaster COPD-related orthologs

2021 ◽  
Author(s):  
Erasmia Rouka ◽  
Natalia Gourgoulianni ◽  
Stefan Lüpold ◽  
Chrissi Hatzoglou ◽  
Konstantinos I. Gourgoulianis ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Human Gene ◽  
Homo Sapiens ◽  
Gene List ◽  
Wnt Signaling Pathway ◽  
Model Organism ◽  
Fruit Fly ◽  
Airway Epithelial Cells ◽  
Chronic Obstructive ◽  
Beta Catenin

The significant similarities in airway epithelial cells between mammals and the fruit fly Drosophila melanogaster have rendered the latter an important model organism for studies of chronic inflammatory lung diseases. Focusing on the chronic obstructive pulmonary disease (COPD), we here mapped human gene orthologs associated with this disease in D. melanogaster to identify functionally equivalent genes for immediate, further screening with the fruit fly model. The DIOPT-DIST tool was accessed for the prediction of the COPD-associated orthologs between humans and Drosophila. Enrichment analyses with respect to pathways of the retrieved functional homologs were performed using the ToppFun and FlyMine tools, identifying 73 unique human genes as well as 438 fruit fly genes. The ToppFun analysis verified that the human gene list is associated with COPD phenotypes. Further, the FlyMine investigation highlighted that the Drosophila genes are functionally connected mainly with the 'ABC-family proteins mediated transport' and the 'beta-catenin independent WNT signaling pathway'. These results suggest an evolutionarily conserved role towards responses to inhaled toxicants and CO2 in both species. We reason that the predicted orthologous genes should be further studied in the Drosophila models of cigarette smoke-induced COPD.

scholarly journals FlyBase: updates to the Drosophila melanogaster knowledge base

2020 ◽  
Vol 49 (D1) ◽  
pp. D899-D907 ◽  
Author(s):  
Aoife Larkin ◽  
Steven J Marygold ◽  
Giulia Antonazzo ◽  
Helen Attrill ◽  
Gilberto dos Santos ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Knowledge Base ◽  
Fast Track ◽  
Model Organism ◽  
Disease Models ◽  
Online Database ◽  
Experimental Tool

Abstract FlyBase (flybase.org) is an essential online database for researchers using Drosophila melanogaster as a model organism, facilitating access to a diverse array of information that includes genetic, molecular, genomic and reagent resources. Here, we describe the introduction of several new features at FlyBase, including Pathway Reports, paralog information, disease models based on orthology, customizable tables within reports and overview displays (‘ribbons’) of expression and disease data. We also describe a variety of recent important updates, including incorporation of a developmental proteome, upgrades to the GAL4 search tab, additional Experimental Tool Reports, migration to JBrowse for genome browsing and improvements to batch queries/downloads and the Fast-Track Your Paper tool.

scholarly journals Influence of Dopamine on Fluorescent Advanced Glycation End Products Formation Using Drosophila melanogaster

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 453
Author(s):  
Ana Filošević Vujnović ◽  
Katarina Jović ◽  
Emanuel Pištan ◽  
Rozi Andretić Waldowski
Keyword(s):  
Drosophila Melanogaster ◽  
Advanced Glycation End Products ◽  
Model Organism ◽  
Covalent Modification ◽  
Advanced Glycation ◽  
Biomarkers Of Aging ◽  
Glycation End Products ◽  
End Products

Non-enzymatic glycation and covalent modification of proteins leads to Advanced Glycation End products (AGEs). AGEs are biomarkers of aging and neurodegenerative disease, and can be induced by impaired neuronal signaling. The objective of this study was to investigate if manipulation of dopamine (DA) in vitro using the model protein, bovine serum albumin (BSA), and in vivo using the model organism Drosophila melanogaster, influences fluorescent AGEs (fAGEs) formation as an indicator of dopamine-induced oxidation events. DA inhibited fAGEs-BSA synthesis in vitro, suggesting an anti-oxidative effect, which was not observed when flies were fed DA. Feeding flies cocaine and methamphetamine led to increased fAGEs formation. Mutants lacking the dopaminergic transporter or the D1-type showed further elevation of fAGEs accumulation, indicating that the long-term perturbation in DA function leads to higher production of fAGEs. To confirm that DA has oxidative properties in vivo, we fed flies antioxidant quercetin (QUE) together with methamphetamine. QUE significantly decreased methamphetamine-induced fAGEs formation suggesting that the perturbation of DA function in vivo leads to increased oxidation. These findings present arguments for the use of fAGEs as a biomarker of DA-associated neurodegenerative changes and for assessment of antioxidant interventions such as QUE treatment.

scholarly journals Quantitative investigation reveals distinct phases in Drosophila sleep

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Xiaochan Xu ◽  
Wei Yang ◽  
Binghui Tian ◽  
Xiuwen Sui ◽  
Weilai Chi ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
General Pattern ◽  
Model Organism ◽  
Infrared Camera ◽  
Fruit Fly ◽  
Genetic Dissection ◽  
Power Law Distribution ◽  
Quantitative Investigation ◽  
Waking Up ◽  
Set Up

AbstractThe fruit fly, Drosophila melanogaster, has been used as a model organism for the molecular and genetic dissection of sleeping behaviors. However, most previous studies were based on qualitative or semi-quantitative characterizations. Here we quantified sleep in flies. We set up an assay to continuously track the activity of flies using infrared camera, which monitored the movement of tens of flies simultaneously with high spatial and temporal resolution. We obtained accurate statistics regarding the rest and sleep patterns of single flies. Analysis of our data has revealed a general pattern of rest and sleep: the rest statistics obeyed a power law distribution and the sleep statistics obeyed an exponential distribution. Thus, a resting fly would start to move again with a probability that decreased with the time it has rested, whereas a sleeping fly would wake up with a probability independent of how long it had slept. Resting transits to sleeping at time scales of minutes. Our method allows quantitative investigations of resting and sleeping behaviors and our results provide insights for mechanisms of falling into and waking up from sleep.

scholarly journals Repeated stress exposure results in a survival–reproduction trade-off in Drosophila melanogaster

2009 ◽  
Vol 277 (1683) ◽  
pp. 963-969 ◽  
Author(s):  
Katie E. Marshall ◽  
Brent J. Sinclair
Keyword(s):  
Drosophila Melanogaster ◽  
Model Organism ◽  
Intrinsic Rate ◽  
Intrinsic Rate Of Increase ◽  
Stress Exposure ◽  
Trade Off ◽  
Repeated Stress ◽  
Rate Of Increase ◽  
In The Wild ◽  
Future Reproduction

While insect cold tolerance has been well studied, the vast majority of work has focused on the effects of a single cold exposure. However, many abiotic environmental stresses, including temperature, fluctuate within an organism's lifespan. Given that organisms may trade-off survival at the cost of future reproduction, we investigated the effects of multiple cold exposures on survival and fertility in the model organism Drosophila melanogaster . We found that multiple cold exposures significantly decreased mortality compared with the same length of exposure in a single sustained bout, but significantly decreased fecundity (as measured by r , the intrinsic rate of increase) as well, owing to a shift in sex ratio. This change was reflected in a long-term decrease in glycogen stores in multiply exposed flies, while a brief effect on triglyceride stores was observed, suggesting flies are reallocating energy stores. Given that many environments are not static, this trade-off indicates that investigating the effects of repeated stress exposure is important for understanding and predicting physiological responses in the wild.

scholarly journals Genetic variation in Drosophila melanogaster pathogen susceptibility

Parasitology ◽  
2006 ◽  
Vol 132 (6) ◽  
pp. 767-773 ◽  
Author(s):  
M. C. TINSLEY ◽  
S. BLANFORD ◽  
F. M. JIGGINS
Keyword(s):  
Biological Control ◽  
Drosophila Melanogaster ◽  
Genetic Variation ◽  
Model Organism ◽  
Resistance Evolution ◽  
Control Programmes ◽  
Host Ecology ◽  
Insect Pathogens ◽  
Immunological Research ◽  
Pathogen Exposure

Genetic variation in susceptibility to pathogens is a central concern both to evolutionary and medical biologists, and for the implementation of biological control programmes. We have investigated the extent of such variation in Drosophila melanogaster, a major model organism for immunological research. We found that within populations, different Drosophila genotypes show wide-ranging variation in their ability to survive infection with the entomopathogenic fungus Beauveria bassiana. Furthermore, striking divergence in susceptibility has occurred between genotypes from temperate and tropical African locations. We hypothesize that this may have been driven by adaptation to local differences in pathogen exposure or host ecology. Genetic variation within populations may be maintained by temporal or spatial variation in the costs and benefits of pathogen defence. Insect pathogens are employed widely as biological control agents and entomopathogenic fungi are currently being developed for reducing malaria transmission by mosquitoes. Our data highlight the need for concern about resistance evolution to these novel biopesticides in vector populations.

scholarly journals Definition of a RACK1 Interaction Network in Drosophila melanogaster Using SWATH-MS

2017 ◽  
Vol 7 (7) ◽  
pp. 2249-2258 ◽  
Author(s):  
Lauriane Kuhn ◽  
Karim Majzoub ◽  
Evelyne Einhorn ◽  
Johana Chicher ◽  
Julien Pompon ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Activated Protein C ◽  
Model Organism ◽  
Interaction Network ◽  
Added Value ◽  
Label Free ◽  
Nucleic Acid Binding ◽  
Entry Site

Abstract Receptor for Activated protein C kinase 1 (RACK1) is a scaffold protein that has been found in association with several signaling complexes, and with the 40S subunit of the ribosome. Using the model organism Drosophila melanogaster, we recently showed that RACK1 is required at the ribosome for internal ribosome entry site (IRES)-mediated translation of viruses. Here, we report a proteomic characterization of the interactome of RACK1 in Drosophila S2 cells. We carried out Label-Free quantitation using both Data-Dependent and Data-Independent Acquisition (DDA and DIA, respectively) and observed a significant advantage for the Sequential Window Acquisition of all THeoretical fragment-ion spectra (SWATH) method, both in terms of identification of interactants and quantification of low abundance proteins. These data represent the first SWATH spectral library available for Drosophila and will be a useful resource for the community. A total of 52 interacting proteins were identified, including several molecules involved in translation such as structural components of the ribosome, factors regulating translation initiation or elongation, and RNA binding proteins. Among these 52 proteins, 15 were identified as partners by the SWATH strategy only. Interestingly, these 15 proteins are significantly enriched for the functions translation and nucleic acid binding. This enrichment reflects the engagement of RACK1 at the ribosome and highlights the added value of SWATH analysis. A functional screen did not reveal any protein sharing the interesting properties of RACK1, which is required for IRES-dependent translation and not essential for cell viability. Intriguingly however, 10 of the RACK1 partners identified restrict replication of Cricket paralysis virus (CrPV), an IRES-containing virus.

scholarly journals Recurrent Collection of Drosophila melanogaster from Wild African Environments and Genomic Insights into Species History

2019 ◽  
Vol 37 (3) ◽  
pp. 627-638 ◽  
Author(s):  
Quentin D Sprengelmeyer ◽  
Suzan Mansourian ◽  
Jeremy D Lange ◽  
Daniel R Matute ◽  
Brandon S Cooper ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Demographic History ◽  
Central Africa ◽  
Model Organism ◽  
Sub Saharan Africa ◽  
Wilderness Areas ◽  
Southern Central ◽  
History Of ◽  
Sub Saharan ◽  
Improved Model

Abstract A long-standing enigma concerns the geographic and ecological origins of the intensively studied vinegar fly, Drosophila melanogaster. This globally distributed human commensal is thought to originate from sub-Saharan Africa, yet until recently, it had never been reported from undisturbed wilderness environments that could reflect its precommensal niche. Here, we document the collection of 288 D. melanogaster individuals from multiple African wilderness areas in Zambia, Zimbabwe, and Namibia. The presence of D. melanogaster in these remote woodland environments is consistent with an ancestral range in southern-central Africa, as opposed to equatorial regions. After sequencing the genomes of 17 wilderness-collected flies collected from Kafue National Park in Zambia, we found reduced genetic diversity relative to town populations, elevated chromosomal inversion frequencies, and strong differences at specific genes including known insecticide targets. Combining these genomes with existing data, we probed the history of this species’ geographic expansion. Demographic estimates indicated that expansion from southern-central Africa began ∼13,000 years ago, with a Saharan crossing soon after, but expansion from the Middle East into Europe did not begin until roughly 1,800 years ago. This improved model of demographic history will provide an important resource for future evolutionary and genomic studies of this key model organism. Our findings add context to the history of D. melanogaster, while opening the door for future studies on the biological basis of adaptation to human environments.

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