scholarly journals Phenotypical Effect of Phosphodiesterase 5 (PDE5) Inhibitor on Behavioral Activities of Fruit Fly Drosophila melanogaster

2021 ◽  
Vol 12 (1) ◽  
pp. 222-229

Phosphodiesterase 5 (PDE5) inhibitor is a class of drugs currently used to treat erectile dysfunction. Physiologically, inhibition of PDE5 may lead to vasodilation, blood flow increment, and penile erection. However, PDE5 inhibitors have been reported not only to modify the function of the male reproductive organ but also to influence other physiological systems. To explore the effect of PDE5 inhibitor on metazoan physiological systems, a fruit fly (Drosophila melanogaster) model organism is used since the catalytic domain of fruit fly PDE5/6 shares a high similarity of amino acid sequence (58%) with the PDE5 of humans. This study aimed to investigate whether the effect of PDE5 inhibition by sildenafil is phenotypically observable as changes in the behavioral states. Two behavioral phenotypes of D. melanogaster, negative geotaxis, and ethanol sensitivity, were used as test parameters in this explorative study. The results demonstrated that sildenafil had a significant effect on reducing locomotor activity, as reflected by negative geotaxis assay, but it had no influence on the fruit fly sensitivity to ethanol. Taken together, our results suggested that PDE5 inhibition might impair the physiological condition of the metazoan species. Also, an explorative study using D. melanogaster might offer valuable insight as a model organism in the discovery and repurposing approach of PDE5 inhibitor.

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Xiaochan Xu ◽  
Wei Yang ◽  
Binghui Tian ◽  
Xiuwen Sui ◽  
Weilai Chi ◽  
...  

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.


2002 ◽  
Vol 79 (2) ◽  
pp. 111-118 ◽  
Author(s):  
K. NAGA MOHAN ◽  
PARAMITA RAY ◽  
H. SHARAT CHANDRA

The co-occurrence of three chromosome-wide phenomena – imprinting, facultative heterochromatization and diffuse centromere – in the mealybug Planococcus lilacinus makes investigation of the genomics of this species an attractive prospect. In order to estimate the complexity of the genome of this species, 300 random stretches of its DNA, constituting ∼0·1% of the genome, were sequenced. Coding sequences appear to constitute ∼53·5%, repeat sequences ∼44·5% and non-coding single-copy sequences ∼2% of the genome. The proportion of repetitive sequences in the mealybug is higher than that in the fruit fly Drosophila melanogaster (∼30%). The mealybug genome (∼220 Mb) is about 1·3 times the size of the fly genome (∼165 Mb) and its GC content (∼35%) less than that of the fly genome (∼40%). The relative abundance of various dinucleotides, as analysed by the method of Gentles and Karlin, shows that the dinucleotide signatures of the two species are moderately similar and that in the mealybug there is neither over-representation nor under-representation of any dinucleotide.


Author(s):  
Abeer Mohbeddin ◽  
Nawar Haj Ahmed ◽  
Layla Kamareddine

Apart from its traditional role in disease control, recent body of evidence has implicated a role of the immune system in regulating metabolic homeostasis. Owing to the importance of this “immune-metabolic alignment” in dictating a state of health or disease, a proper mechanistic understanding of this alignment is crucial in opening up for promising therapeutic approaches against a broad range of chronic, metabolic, and inflammatory disorders like obesity, diabetes, and inflammatory bowel syndrome. In this project, we addressed the role of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) innate immune pathway in regulating different metabolic parameters using the Drosophila melanogaster (DM) fruit fly model organism. Mutant JAK/STAT pathway flies with a systemic knockdown of either Domeless (Dome) [domeG0282], the receptor that activates JAK/STAT signaling, or the signal-transducer and activator of transcription protein at 92E (Stat92E) [stat92EEY10528], were used. The results of the study revealed that blocking JAK/STAT signaling alters the metabolic profile of mutant flies. Both domeG0282 and stat92EEY10528 mutants had an increase in body weight, lipid deprivation from their fat body (lipid storage organ in flies), irregular accumulation of lipid droplets in the gut, systemic elevation of glucose and triglyceride levels, and differential down-regulation in the relative gene expression of different peptide hormones (Tachykinin, Allatostatin C, and Diuretic hormone 31) known to regulate metabolic homeostasis in flies. Because the JAK/STAT pathway is evolutionary conserved between invertebrates and vertebrates, our potential findings in the fruit fly serves as a platform for further immune-metabolic translational studies in more complex mammalian systems including humans.


2021 ◽  
Vol 15 ◽  
Author(s):  
Timothy D. Wiggin ◽  
Yungyi Hsiao ◽  
Jeffrey B. Liu ◽  
Robert Huber ◽  
Leslie C. Griffith

Maladaptive operant conditioning contributes to development of neuropsychiatric disorders. Candidate genes have been identified that contribute to this maladaptive plasticity, but the neural basis of operant conditioning in genetic model organisms remains poorly understood. The fruit fly Drosophila melanogaster is a versatile genetic model organism that readily forms operant associations with punishment stimuli. However, operant conditioning with a food reward has not been demonstrated in flies, limiting the types of neural circuits that can be studied. Here we present the first sucrose-reinforced operant conditioning paradigm for flies. In the paradigm, flies walk along a Y-shaped track with reward locations at the terminus of each hallway. When flies turn in the reinforced direction at the center of the track, they receive a sucrose reward at the end of the hallway. Only flies that rest early in training learn the reward contingency normally. Flies rewarded independently of their behavior do not form a learned association but have the same amount of rest as trained flies, showing that rest is not driven by learning. Optogenetically-induced sleep does not promote learning, indicating that sleep itself is not sufficient for learning the operant task. We validated the sensitivity of this assay to detect the effect of genetic manipulations by testing the classic learning mutant dunce. Dunce flies are learning-impaired in the Y-Track task, indicating a likely role for cAMP in the operant coincidence detector. This novel training paradigm will provide valuable insight into the molecular mechanisms of disease and the link between sleep and learning.


2019 ◽  
Vol 11 (12) ◽  
pp. 425-443 ◽  
Author(s):  
Alireza Zabihihesari ◽  
Arthur J Hilliker ◽  
Pouya Rezai

Abstract The fruit fly or Drosophila melanogaster has been used as a promising model organism in genetics, developmental and behavioral studies as well as in the fields of neuroscience, pharmacology, and toxicology. Not only all the developmental stages of Drosophila, including embryonic, larval, and adulthood stages, have been used in experimental in vivo biology, but also the organs, tissues, and cells extracted from this model have found applications in in vitro assays. However, the manual manipulation, cellular investigation and behavioral phenotyping techniques utilized in conventional Drosophila-based in vivo and in vitro assays are mostly time-consuming, labor-intensive, and low in throughput. Moreover, stimulation of the organism with external biological, chemical, or physical signals requires precision in signal delivery, while quantification of neural and behavioral phenotypes necessitates optical and physical accessibility to Drosophila. Recently, microfluidic and lab-on-a-chip devices have emerged as powerful tools to overcome these challenges. This review paper demonstrates the role of microfluidic technology in Drosophila studies with a focus on both in vivo and in vitro investigations. The reviewed microfluidic devices are categorized based on their applications to various stages of Drosophila development. We have emphasized technologies that were utilized for tissue- and behavior-based investigations. Furthermore, the challenges and future directions in Drosophila-on-a-chip research, and its integration with other advanced technologies, will be discussed.


2020 ◽  
Vol 11 ◽  
Author(s):  
Óscar M. Lezcano ◽  
Miriam Sánchez-Polo ◽  
José L. Ruiz ◽  
Elena Gómez-Díaz

The principles and function of chromatin and nuclear architecture have been extensively studied in model organisms, such as Drosophila melanogaster. However, little is known about the role of these epigenetic processes in transcriptional regulation in other insects including mosquitoes, which are major disease vectors and a worldwide threat for human health. Some of these life-threatening diseases are malaria, which is caused by protozoan parasites of the genus Plasmodium and transmitted by Anopheles mosquitoes; dengue fever, which is caused by an arbovirus mainly transmitted by Aedes aegypti; and West Nile fever, which is caused by an arbovirus transmitted by Culex spp. In this contribution, we review what is known about chromatin-associated mechanisms and the 3D genome structure in various mosquito vectors, including Anopheles, Aedes, and Culex spp. We also discuss the similarities between epigenetic mechanisms in mosquitoes and the model organism Drosophila melanogaster, and advocate that the field could benefit from the cross-application of state-of-the-art functional genomic technologies that are well-developed in the fruit fly. Uncovering the mosquito regulatory genome can lead to the discovery of unique regulatory networks associated with the parasitic life-style of these insects. It is also critical to understand the molecular interactions between the vectors and the pathogens that they transmit, which could hold the key to major breakthroughs on the fight against mosquito-borne diseases. Finally, it is clear that epigenetic mechanisms controlling mosquito environmental plasticity and evolvability are also of utmost importance, particularly in the current context of globalization and climate change.


Author(s):  
Sumira Malik

Homo sapiens and Drosophila malenogaster, a fruit fly, share genetic homology in development process regulated through fundamental biological pathways and conserved mechanisms conserved as a process of evolution among these species. Drosophila melanogaster is an eminent model organism to study diverse biological species. In this chapter, the use of wide variety of nano particles and their impact on Drosophila melanogastsr's development, longevity, characteristics of reproduction has been studied.


2018 ◽  
Vol 80 (4) ◽  
pp. 272-277
Author(s):  
Jennifer Broo ◽  
Jessica Mahoney ◽  
Julie Bokor ◽  
Daniel Hahn

Climate change can drive evolution. This connection is clear both historically and in modern times. The three-lesson curriculum described below provides opportunities for students to make connections between climate change and evolution through various modes of inquiry and self-investigation. Students examine how genetic variation may either facilitate or limit the ability for species to survive changing climates through work with the model organism Drosophila melanogaster. Students are asked to layer new understanding of the mechanisms of evolution onto their observations of genetic variation in fruit fly thermotolerance, and then synthesize this information to make predictions regarding the survival of species threatened by climate change.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Annie Park ◽  
Tracy Tran ◽  
Elizabeth A Scheuermann ◽  
Dean P Smith ◽  
Nigel S Atkinson

For decades, numerous researchers have documented the presence of the fruit fly or Drosophila melanogaster on alcohol-containing food sources. Although fruit flies are a common laboratory model organism of choice, there is relatively little understood about the ethological relationship between flies and ethanol. In this study, we find that when male flies inhabit ethanol-containing food substrates they become more aggressive. We identify a possible mechanism for this behavior. The odor of ethanol potentiates the activity of sensory neurons in response to an aggression-promoting pheromone. Finally, we observed that the odor of ethanol also promotes attraction to a food-related citrus odor. Understanding how flies interact with the complex natural environment they inhabit can provide valuable insight into how different natural stimuli are integrated to promote fundamental behaviors.


2014 ◽  
Vol 306 (5) ◽  
pp. L442-L452 ◽  
Author(s):  
Zhichao Zhou ◽  
Vincent J. de Beer ◽  
Daphne de Wijs-Meijler ◽  
Shawn B. Bender ◽  
Maaike Hoekstra ◽  
...  

Both phosphodiesterase 5 (PDE5) inhibition and endothelin (ET) receptor blockade have been shown to induce pulmonary vasodilation. However, little is known about the effect of combined blockade of these two vasoconstrictor pathways. Since nitric oxide (NO) exerts its pulmonary vasodilator influence via production of cyclic guanosine monophosphate (cGMP) as well as through inhibition of ET, we hypothesized that interaction between the respective signaling pathways precludes an additive vasodilator effect. We tested this hypothesis in chronically instrumented swine exercising on a treadmill by comparing the vasodilator effect of the PDE5 inhibitor EMD360527, the ETA/ETB antagonist tezosentan, and combined EMD360527 and tezosentan. In the systemic circulation, vasodilation by tezosentan and EMD360527 was additive, both at rest and during exercise, resulting in a 17 ± 2% drop in blood pressure. In the pulmonary circulation, both EMD360527 and tezosentan produced vasodilation. However, tezosentan produced no additional pulmonary vasodilation in the presence of EMD360527, either at rest or during exercise. Moreover, in isolated preconstricted porcine pulmonary small arteries (∼300 μm) EMD360527 (1 nM–10 μM) induced dose-dependent vasodilation, whereas tezosentan (1 nM–10 μM) failed to elicit vasodilation irrespective of the presence of EMD360527. However, both PDE5 inhibition and 8Br-cGMP, but not 8Br-cAMP, blunted pulmonary small artery contraction to ET and its precursor Big ET in vitro. In conclusion, in healthy swine, either at rest or during exercise, PDE5 inhibition and the associated increase in cGMP produce pulmonary vasodilation that is mediated in part through inhibition of the ET pathway, thereby precluding an additional vasodilator effect of ETA/ETB receptor blockade in the presence of PDE5 inhibition.


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