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Kidney360 May 2024
Topics: Animals; Disease Models, Animal; Dent Disease; Drosophila melanogaster; Humans
PubMed: 38814756
DOI: 10.34067/KID.0000000000000441 -
ELife May 2024To navigate their environment, insects need to keep track of their orientation. Previous work has shown that insects encode their head direction as a sinusoidal activity...
To navigate their environment, insects need to keep track of their orientation. Previous work has shown that insects encode their head direction as a sinusoidal activity pattern around a ring of neurons arranged in an eight-column structure. However, it is unclear whether this sinusoidal encoding of head direction is just an evolutionary coincidence or if it offers a particular functional advantage. To address this question, we establish the basic mathematical requirements for direction encoding and show that it can be performed by many circuits, all with different activity patterns. Among these activity patterns, we prove that the sinusoidal one is the most noise-resilient, but only when coupled with a sinusoidal connectivity pattern between the encoding neurons. We compare this predicted optimal connectivity pattern with anatomical data from the head direction circuits of the locust and the fruit fly, finding that our theory agrees with experimental evidence. Furthermore, we demonstrate that our predicted circuit can emerge using Hebbian plasticity, implying that the neural connectivity does not need to be explicitly encoded in the genetic program of the insect but rather can emerge during development. Finally, we illustrate that in our theory, the consistent presence of the eight-column organisation of head direction circuits across multiple insect species is not a chance artefact but instead can be explained by basic evolutionary principles.
Topics: Animals; Head; Grasshoppers; Neurons; Insecta; Models, Neurological; Drosophila melanogaster
PubMed: 38814703
DOI: 10.7554/eLife.91533 -
Nature Communications May 2024Although the effects of genetic and environmental perturbations on multicellular organisms are rarely restricted to single phenotypic layers, our current understanding...
Although the effects of genetic and environmental perturbations on multicellular organisms are rarely restricted to single phenotypic layers, our current understanding of how developmental programs react to these challenges remains limited. Here, we have examined the phenotypic consequences of disturbing the bicoid regulatory network in early Drosophila embryos. We generated flies with two extra copies of bicoid, which causes a posterior shift of the network's regulatory outputs and a decrease in fitness. We subjected these flies to EMS mutagenesis, followed by experimental evolution. After only 8-15 generations, experimental populations have normalized patterns of gene expression and increased survival. Using a phenomics approach, we find that populations were normalized through rapid increases in embryo size driven by maternal changes in metabolism and ovariole development. We extend our results to additional populations of flies, demonstrating predictability. Together, our results necessitate a broader view of regulatory network evolution at the systems level.
Topics: Animals; Drosophila Proteins; Gene Expression Regulation, Developmental; Gene Regulatory Networks; Female; Drosophila melanogaster; Gene Dosage; Homeodomain Proteins; Phenotype; Male; Embryo, Nonmammalian; Drosophila; Mutagenesis; Trans-Activators
PubMed: 38811562
DOI: 10.1038/s41467-024-48960-4 -
Nature Communications May 2024Gene drive systems could be a viable strategy to prevent pathogen transmission or suppress vector populations by propagating drive alleles with super-Mendelian...
Gene drive systems could be a viable strategy to prevent pathogen transmission or suppress vector populations by propagating drive alleles with super-Mendelian inheritance. CRISPR-based homing gene drives convert wild type alleles into drive alleles in heterozygotes with Cas9 and gRNA. It is thus desirable to identify Cas9 promoters that yield high drive conversion rates, minimize the formation rate of resistance alleles in both the germline and the early embryo, and limit somatic Cas9 expression. In Drosophila, the nanos promoter avoids leaky somatic expression, but at the cost of high embryo resistance from maternally deposited Cas9. To improve drive efficiency, we test eleven Drosophila melanogaster germline promoters. Some achieve higher drive conversion efficiency with minimal embryo resistance, but none completely avoid somatic expression. However, such somatic expression often does not carry detectable fitness costs for a rescue homing drive targeting a haplolethal gene, suggesting somatic drive conversion. Supporting a 4-gRNA suppression drive, one promoter leads to a low drive equilibrium frequency due to fitness costs from somatic expression, but the other outperforms nanos, resulting in successful suppression of the cage population. Overall, these Cas9 promoters hold advantages for homing drives in Drosophila species and may possess valuable homologs in other organisms.
Topics: Animals; Promoter Regions, Genetic; Drosophila melanogaster; Drosophila Proteins; Gene Drive Technology; CRISPR-Cas Systems; Germ Cells; RNA, Guide, CRISPR-Cas Systems; Animals, Genetically Modified; CRISPR-Associated Protein 9; Alleles; Female; Male; RNA-Binding Proteins
PubMed: 38811556
DOI: 10.1038/s41467-024-48874-1 -
ELife May 2024is a powerful model to study how lipids affect spermatogenesis. Yet, the contribution of neutral lipids, a major lipid group which resides in organelles called lipid...
is a powerful model to study how lipids affect spermatogenesis. Yet, the contribution of neutral lipids, a major lipid group which resides in organelles called lipid droplets (LD), to sperm development is largely unknown. Emerging evidence suggests LD are present in the testis and that loss of neutral lipid- and LD-associated genes causes subfertility; however, key regulators of testis neutral lipids and LD remain unclear. Here, we show LD are present in early-stage somatic and germline cells within the testis. We identified a role for triglyceride lipase () in regulating testis LD, and found that whole-body loss of leads to defects in sperm development. Importantly, these represent cell-autonomous roles for in regulating testis LD and spermatogenesis. Because lipidomic analysis of mutants revealed excess triglyceride accumulation, and spermatogenic defects in mutants were rescued by genetically blocking triglyceride synthesis, our data suggest that -mediated regulation of triglyceride influences sperm development. This identifies triglyceride as an important neutral lipid that contributes to sperm development, and reveals a key role for in regulating testis triglyceride levels during spermatogenesis.
Topics: Spermatogenesis; Animals; Male; Triglycerides; Drosophila Proteins; Testis; Drosophila melanogaster; Lipase; Lipid Droplets; Spermatozoa
PubMed: 38805376
DOI: 10.7554/eLife.87523 -
Frontiers in Immunology 2024Since infections with antibiotic-resistant bacteria cause increasing problems worldwide, the identification of alternative therapies is of great importance....
Since infections with antibiotic-resistant bacteria cause increasing problems worldwide, the identification of alternative therapies is of great importance. Plant-derived bioactives, including allyl-isothiocyanate (AITC), have received attention for their antimicrobial properties. The present study therefore investigates the impact of AITC on survival and antimicrobial peptide (AMP) levels in challenged with the fly pathogenic bacteria subsp. and . AITC, a sulfur-containing compound derived from glucosinolates, exhibits antimicrobial properties and has been suggested to modulate AMP expression. By using , we demonstrate that AITC treatment resulted in a concentration-dependent decrease of survival rates among female flies, particularly in the presence of the Gram-negative bacterium subsp. , whereas AITC did not affect survival in male flies. Despite the ability of isothiocyanates to induce AMP expression in cell culture, we did not detect significant changes in AMP mRNA levels in infected flies exposed to AITC. Our findings suggest sex-specific differences in response to AITC treatment and bacterial infections, underlining the complexity of host-pathogen interactions and potential limitations of AITC as a preventive or therapeutic compound at least in models of bacterial infections.
Topics: Animals; Isothiocyanates; Drosophila melanogaster; Female; Male; Antimicrobial Peptides; Pectobacterium carotovorum; Drosophila Proteins
PubMed: 38803500
DOI: 10.3389/fimmu.2024.1404086 -
Wellcome Open Research 2024We present a genome assembly from an individual male (drosophilid fruit fly, Arthropoda; Insecta; Diptera; Drosophilidae). The genome sequence is 223.9 megabases in...
We present a genome assembly from an individual male (drosophilid fruit fly, Arthropoda; Insecta; Diptera; Drosophilidae). The genome sequence is 223.9 megabases in span. Most of the assembly is scaffolded into 7 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 16.14 kilobases in length. Gene annotation of this assembly on Ensembl identified 18,973 protein coding genes.
PubMed: 38800521
DOI: 10.12688/wellcomeopenres.20634.1 -
Wellcome Open Research 2023We present a genome assembly from an individual male (drosophilid fruit fly; Arthropoda; Insecta; Diptera; Drosophilidae). The genome sequence is 181.1 megabases in...
We present a genome assembly from an individual male (drosophilid fruit fly; Arthropoda; Insecta; Diptera; Drosophilidae). The genome sequence is 181.1 megabases in span. Most of the assembly is scaffolded into 7 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 16.15 kilobases in length.
PubMed: 38798998
DOI: 10.12688/wellcomeopenres.20035.1 -
Narra J Apr 2024Aging is commonly characterized by a decline in the physiological functioning of the body organs, with one hallmark being the impairment of intestinal function, leading...
Aging is commonly characterized by a decline in the physiological functioning of the body organs, with one hallmark being the impairment of intestinal function, leading to increased intestinal permeability known as leaky gut. The aim of this study was to investigate the potential of curcumin to prevent the development of leaky gut in utilizing the smurf fly method. In this study, flies aged 3-5 days underwent a 10-day dextran sulfate sodium (DSS) treatment to induce intestinal permeability, followed by a smurf assay using brilliant blue dye and locomotor testing the next day. Flies displaying the smurf phenotype were divided into four groups: untreated control and curcumin-treated (10 μM, 50 μM, and 250 μM). After 21 days of treatment, flies were reassessed for the smurf phenotype and underwent locomotor testing. On day 23, flies were subjected to RT-qPCR analysis. By inducing increased intestinal permeability through the administration of DSS, a higher proportion of flies exhibiting the smurf phenotype and a reduced survival rate in the DSS-treated group were observed. Such phenotypes were reversed, decreased number of flies displaying the smurf phenotype and improved fly survival, upon the incorporation of curcumin in the fly food at concentrations of 10, 50, and 250 μM. Subsequent molecular analysis revealed upregulated expression of , and genes, while no significant changes were observed in the expression of , and genes following treatment with curcumin at high concentration. Overall, our findings provide insight into the potential effect of curcumin to alleviate the phenotypical features associated with DSS-induced leaky gut, possibly via the selective regulation of aging-related genes.
Topics: Animals; Curcumin; Drosophila melanogaster; Permeability; Dextran Sulfate; Phenotype
PubMed: 38798865
DOI: 10.52225/narra.v4i1.743 -
Narra J Apr 2024It is widely acknowledged that smoking exacerbates the severity of infectious diseases. A presumed mechanism involves the damage inflicted by tobacco smoke on the organs...
It is widely acknowledged that smoking exacerbates the severity of infectious diseases. A presumed mechanism involves the damage inflicted by tobacco smoke on the organs of host organisms. In this study, an alternative hypothesis was explored: smoking enhances the virulence of bacteria. This possibility was investigated using as the model bacteria and as the host organism. Our inquiry focused on the potential gene expression changes in subsequent to exposure to tobacco smoke extracts. Analysis of the transcription promoter activity of genes encoding proteins within the two-component system, a regulatory machinery governing gene expression, revealed the suppression of thirteen out of 23 promoters in response to tobacco smoke extracts. Subsequently, was infected with exposed to tobacco smoke extracts or left untreated. Interestingly, there were no significant differences observed in the survival periods of following infection with , whether treated or untreated with tobacco smoke extracts. Contrary to the initial hypothesis, the findings suggest that while tobacco smoke extracts alter gene expression in , these changes do not appear to impact bacterial virulence. Although this study has illuminated the influence of tobacco smoke extracts on the gene expression of , further analyses are necessary to elucidate the implications of these changes. Nevertheless, the results imply that smoking affects not only host organisms but may also exert influence on invading bacteria.
Topics: Escherichia coli; Animals; Virulence; Nicotiana; Drosophila; Gene Expression Regulation, Bacterial; Smoke; Virulence Factors
PubMed: 38798851
DOI: 10.52225/narra.v4i1.754