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1.
Sci Total Environ ; 804: 150254, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34798758

RESUMO

Although the toxicity of neonicotinoid insecticides has been demonstrated in several studies, the information on metabolism, behavior, and health risk remains limited and has raised concerns about its potential toxicity. Thus, in this study we assessed the effects of nitenpyram using different sublethal concentrations (one-third and one-tenth of the acute LC50 values) on various developmental and metabolic parameters from gene expression regulation in Drosophila melanogaster (model system used worldwide in ecotoxicological studies). As a result, nitenpyram sublethal concentrations prolonged the developmental time for both pupation and eclosion. Additionally, nitenpyram sublethal concentrations significantly decreased the lifespan, pupation rate, eclosion rate, and production of eggs of D. melanogaster. Moreover, the mRNA expression of genes relevant for development and metabolism was significantly elevated after exposure. Mixed function oxidase enzymes (Cyp12d1), (Cyp9f2), and (Cyp4ae1), hemocyte proliferation (RyR), and immune response (IM4) genes were upregulated, whereas lifespan (Atg7), male mating behavior (Ple), female fertility (Ddc), and lipid metabolism (Sxe2) genes were downregulated. These findings support a solid basis for further research to determine the hazardous effects of nitenpyram on health and the environment.


Assuntos
Proteínas de Drosophila , Drosophilidae , Inseticidas , Praguicidas , Animais , Proteína 7 Relacionada à Autofagia , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophilidae/metabolismo , Feminino , Inseticidas/toxicidade , Masculino , Neonicotinoides , Reprodução , Transcriptoma
3.
Elife ; 102021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34723794

RESUMO

Acoustic signals serve communication within and across species throughout the animal kingdom. Studying the genetics, evolution, and neurobiology of acoustic communication requires annotating acoustic signals: segmenting and identifying individual acoustic elements like syllables or sound pulses. To be useful, annotations need to be accurate, robust to noise, and fast.We here introduce DeepAudioSegmenter (DAS), a method that annotates acoustic signals across species based on a deep-learning derived hierarchical presentation of sound. We demonstrate the accuracy, robustness, and speed of DAS using acoustic signals with diverse characteristics from insects, birds, and mammals. DAS comes with a graphical user interface for annotating song, training the network, and for generating and proofreading annotations. The method can be trained to annotate signals from new species with little manual annotation and can be combined with unsupervised methods to discover novel signal types. DAS annotates song with high throughput and low latency for experimental interventions in realtime. Overall, DAS is a universal, versatile, and accessible tool for annotating acoustic communication signals.


Assuntos
Acústica , Comunicação Animal , Callithrix/fisiologia , Drosophila melanogaster/fisiologia , Etologia/métodos , Camundongos/fisiologia , Aves Canoras/fisiologia , Animais , Feminino , Tentilhões/fisiologia , Masculino , Redes Neurais de Computação
4.
Appl Microbiol Biotechnol ; 105(20): 7721-7730, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34596721

RESUMO

The steadily increasing prevalence of Alzheimer's disease (AD) worldwide and the lack of effective therapeutic agent attract novel therapeutic approach in recent years. In view of the close relationships between gut microbiota and AD, probiotics have been suggested as potential therapeutic options for AD in recent years. The present review discussed the research progresses concerning the effects of probiotics administration to combat AD. A total of 35 studies, including 26 animal model studies and 9 human studies, were included herein. Among the 26 animal model studies, 24 used mice model, and 2 used Caenorhabditis elegans and Drosophila melanogaster AD models, respectively. As for probiotics, a total of 13 studies employed single-strain probiotic, and the rest studies used multi-strain probiotics (ranged from 2 to 9 probiotic strains), 4 used probiotic-fermented milk or probiotic-fermented soybean, 2 studies used engineered probiotic strain, and 4 studies focused on the combined effect of probiotics with AD drug memantine, selenium, or exercise. Bifidobacterium and Lactobacillus species were the most frequently used probiotics in the included studies. Overall, currently available studies showed that probiotic administration conferred neuroprotective benefits and could attenuate cognitive deficits and modulate gut microbiota dysbiosis, which may be related to oxidative and inflammatory pathways. Several perspectives on future studies on this topic are proposed. Thus, probiotics seem to be an attractive approach to combat AD, which deserves to be further studied by well-designed large-scale clinical studies. KEY POINTS: •We discussed the recent progresses concerning the effects of probiotics administration to combat AD. •A total of 35 associated studies consisted of 26 animal model studies and 9 human studies were included. •Most studies found that probiotic administration conferred neuroprotective benefits and could attenuate cognitive deficits.


Assuntos
Doença de Alzheimer , Microbioma Gastrointestinal , Probióticos , Doença de Alzheimer/tratamento farmacológico , Animais , Bifidobacterium , Drosophila melanogaster , Camundongos
5.
BMC Genomics ; 22(1): 771, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34711176

RESUMO

BACKGROUND: Temperature change affects the myriad of concurrent cellular processes in a non-uniform, disruptive manner. While endothermic organisms minimize the challenge of ambient temperature variation by keeping the core body temperature constant, cells of many ectothermic species maintain homeostatic function within a considerable temperature range. The cellular mechanisms enabling temperature acclimation in ectotherms are still poorly understood. At the transcriptional level, the heat shock response has been analyzed extensively. The opposite, the response to sub-optimal temperature, has received lesser attention in particular in animal species. The tissue specificity of transcriptional responses to cool temperature has not been addressed and it is not clear whether a prominent general response occurs. Cis-regulatory elements (CREs), which mediate increased transcription at cool temperature, and responsible transcription factors are largely unknown. RESULTS: The ectotherm Drosophila melanogaster with a presumed temperature optimum around 25 °C was used for transcriptomic analyses of effects of temperatures at the lower end of the readily tolerated range (14-29 °C). Comparative analyses with adult flies and cell culture lines indicated a striking degree of cell-type specificity in the transcriptional response to cool. To identify potential cis-regulatory elements (CREs) for transcriptional upregulation at cool temperature, we analyzed temperature effects on DNA accessibility in chromatin of S2R+ cells. Candidate cis-regulatory elements (CREs) were evaluated with a novel reporter assay for accurate assessment of their temperature-dependency. Robust transcriptional upregulation at low temperature could be demonstrated for a fragment from the pastrel gene, which expresses more transcript and protein at reduced temperatures. This CRE is controlled by the JAK/STAT signaling pathway and antagonizing activities of the transcription factors Pointed and Ets97D. CONCLUSION: Beyond a rich data resource for future analyses of transcriptional control within the readily tolerated range of an ectothermic animal, a novel reporter assay permitting quantitative characterization of CRE temperature dependence was developed. Our identification and functional dissection of the pst_E1 enhancer demonstrate the utility of resources and assay. The functional characterization of this CoolUp enhancer provides initial mechanistic insights into transcriptional upregulation induced by a shift to temperatures at the lower end of the readily tolerated range.


Assuntos
Drosophila melanogaster , Drosophila , Animais , Temperatura Baixa , Drosophila melanogaster/genética , Sequências Reguladoras de Ácido Nucleico , Temperatura
6.
J Vis Exp ; (175)2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34633381

RESUMO

The usefulness of Drosophila as a model organism for the study of human diseases, behaviors and basic biology is unquestionable. Although practical, Drosophila research lacks popularity in developing countries, possibly due to the misinformed idea that establishing a lab and performing relevant experiments with such tiny insects is difficult and requires expensive, specialized apparatuses. Here, we describe how to build an affordable flylab to quantitatively analyze a myriad of behavioral parameters in D. melanogaster, by 3D-printing many of the necessary pieces of equipment. We provide protocols to build in-house vial racks, courtship arenas, apparatuses for locomotor assays, etc., to be used for general fly maintenance and to perform behavioral experiments using adult flies and larvae. We also provide protocols on how to use more sophisticated systems, such as a high resolution oxygraph, to measure mitochondrial oxygen consumption in larval samples, and show its association with behavioral changes in the larvae upon the xenotopic expression of the mitochondrial alternative oxidase (AOX). AOX increases larval activity and mitochondrial leak respiration, and accelerates development at low temperatures, which is consistent with a thermogenic role for the enzyme. We hope these protocols will inspire researchers, especially from developing countries, to use Drosophila to easily combine behavior and mitochondrial metabolism data, which may lead to information on genes and/or environmental conditions that may also regulate human physiology and disease states.


Assuntos
Drosophila melanogaster , Drosophila , Animais , Comportamento Animal , Humanos , Larva , Mitocôndrias
7.
Nat Commun ; 12(1): 5758, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34599173

RESUMO

Various behavioral and cognitive states exhibit circadian variations in animals across phyla including Drosophila melanogaster, in which only ~0.1% of the brain's neurons contain circadian clocks. Clock neurons transmit the timing information to a plethora of non-clock neurons via poorly understood mechanisms. Here, we address the molecular underpinning of this phenomenon by profiling circadian gene expression in non-clock neurons that constitute the mushroom body, the center of associative learning and sleep regulation. We show that circadian clocks drive rhythmic expression of hundreds of genes in mushroom body neurons, including the Neurofibromin 1 (Nf1) tumor suppressor gene and Pka-C1. Circadian clocks also drive calcium rhythms in mushroom body neurons via NF1-cAMP/PKA-C1 signaling, eliciting higher mushroom body activity during the day than at night, thereby promoting daytime wakefulness. These findings reveal the pervasive, non-cell-autonomous circadian regulation of gene expression in the brain and its role in sleep.


Assuntos
Relógios Circadianos/fisiologia , Proteínas de Drosophila/metabolismo , Corpos Pedunculados/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Proteínas Ativadoras de ras GTPase/metabolismo , Animais , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Drosophila melanogaster , Regulação da Expressão Gênica/fisiologia , Modelos Animais , Corpos Pedunculados/citologia , RNA-Seq , Transdução de Sinais/fisiologia , Sono/fisiologia , Vigília/fisiologia
8.
Elife ; 102021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596529

RESUMO

In multiple cell lineages, Delta-Notch signalling regulates cell fate decisions owing to unidirectional signalling between daughter cells. In Drosophila pupal sensory organ lineage, Notch regulates the intra-lineage pIIa/pIIb fate decision at cytokinesis. Notch and Delta that localise apically and basally at the pIIa-pIIb interface are expressed at low levels and their residence time at the plasma membrane is in the order of minutes. How Delta can effectively interact with Notch to trigger signalling from a large plasma membrane area remains poorly understood. Here, we report that the signalling interface possesses a unique apico-basal polarity with Par3/Bazooka localising in the form of nano-clusters at the apical and basal level. Notch is preferentially targeted to the pIIa-pIIb interface, where it co-clusters with Bazooka and its cofactor Sanpodo. Clusters whose assembly relies on Bazooka and Sanpodo activities are also positive for Neuralized, the E3 ligase required for Delta activity. We propose that the nano-clusters act as snap buttons at the new pIIa-pIIb interface to allow efficient intra-lineage signalling.


Assuntos
Divisão Celular , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/metabolismo , Receptores Notch/metabolismo , Órgãos dos Sentidos/metabolismo , Células-Tronco/metabolismo , Animais , Animais Geneticamente Modificados , Linhagem da Célula , Polaridade Celular , Citocinese , Proteínas de Drosophila/genética , Drosophila melanogaster/citologia , Drosophila melanogaster/genética , Regulação da Expressão Gênica no Desenvolvimento , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas de Membrana/genética , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Receptores Notch/genética , Órgãos dos Sentidos/citologia , Transdução de Sinais , Fatores de Tempo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
9.
Int J Mol Sci ; 22(19)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34638607

RESUMO

Asymmetric cell division (ACD) of neural stem cells and progenitors not only renews the stem cell population but also ensures the normal development of the nervous system, producing various types of neurons with different shapes and functions in the brain. One major mechanism to achieve ACD is the asymmetric localization and uneven segregation of intracellular proteins and organelles into sibling cells. Recent studies have demonstrated that liquid-liquid phase separation (LLPS) provides a potential mechanism for the formation of membrane-less biomolecular condensates that are asymmetrically distributed on limited membrane regions. Moreover, mechanical forces have emerged as pivotal regulators of asymmetric neural stem cell division by generating sibling cell size asymmetry. In this review, we will summarize recent discoveries of ACD mechanisms driven by LLPS and mechanical forces.


Assuntos
Divisão Celular Assimétrica/fisiologia , Células-Tronco Neurais/citologia , Células-Tronco Neurais/fisiologia , Animais , Fenômenos Biomecânicos , Divisão Celular/fisiologia , Polaridade Celular/fisiologia , Tamanho Celular , Proteínas de Drosophila/fisiologia , Drosophila melanogaster/citologia , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/fisiologia , Modelos Neurológicos , Miosinas/fisiologia , Neurogênese/fisiologia , Organelas/fisiologia
10.
J Vis Exp ; (175)2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34605807

RESUMO

The genome is organized into topologically associating domains (TADs) delimited by boundaries that isolate interactions between domains. In Drosophila, the mechanisms underlying TAD formation and boundaries are still under investigation. The application of the in-nucleus Hi-C method described here helped to dissect the function of architectural protein (AP)-binding sites at TAD boundaries isolating the Notch gene. Genetic modification of domain boundaries that cause loss of APs results in TAD fusion, transcriptional defects, and long-range topological alterations. These results provided evidence demonstrating the contribution of genetic elements to domain boundary formation and gene expression control in Drosophila. Here, the in-nucleus Hi-C method has been described in detail, which provides important checkpoints to assess the quality of the experiment along with the protocol. Also shown are the required numbers of sequencing reads and valid Hi-C pairs to analyze genomic interactions at different genomic scales. CRISPR/Cas9-mediated genetic editing of regulatory elements and high-resolution profiling of genomic interactions using this in-nucleus Hi-C protocol could be a powerful combination for the investigation of the structural function of genetic elements.


Assuntos
Cromatina , Drosophila , Animais , Núcleo Celular , Drosophila/genética , Drosophila melanogaster/genética , Genômica
11.
BMC Bioinformatics ; 22(1): 516, 2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34688247

RESUMO

BACKGROUND: The origin is the starting site of DNA replication, an extremely vital part of the informational inheritance between parents and children. More importantly, accurately identifying the origin of replication has great application value in the diagnosis and treatment of diseases related to genetic information errors, while the traditional biological experimental methods are time-consuming and laborious. RESULTS: We carried out research on the origin of replication in a variety of eukaryotes and proposed a unique prediction method for each species. Throughout the experiment, we collected data from 7 species, including Homo sapiens, Mus musculus, Drosophila melanogaster, Arabidopsis thaliana, Kluyveromyces lactis, Pichia pastoris and Schizosaccharomyces pombe. In addition to the commonly used sequence feature extraction methods PseKNC-II and Base-content, we designed a feature extraction method based on TF-IDF. Then the two-step method was utilized for feature selection. After comparing a variety of traditional machine learning classification models, the multi-layer perceptron was employed as the classification algorithm. Ultimately, the data and codes involved in the experiment are available at https://github.com/Sarahyouzi/EukOriginPredict . CONCLUSIONS: The prediction accuracy of the training set of the above-mentioned seven species after 100 times fivefold cross validation reach 92.60%, 90.80%, 91.22%, 96.15%, 96.72%, 99.86%, 96.72%, respectively. It denotes that compared with other methods, the methods we designed could accomplish superior performance. In addition, our experiments reveals that the models of multiple species could predict each other with high accuracy, and the results of STREME shows that they have a certain common motif.


Assuntos
Drosophila melanogaster , Eucariotos , Animais , Drosophila melanogaster/genética , Kluyveromyces , Camundongos , Redes Neurais de Computação , Saccharomycetales
12.
Elife ; 102021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34605405

RESUMO

PERK is an endoplasmic reticulum (ER) transmembrane sensor that phosphorylates eIF2α to initiate the Unfolded Protein Response (UPR). eIF2α phosphorylation promotes stress-responsive gene expression most notably through the transcription factor ATF4 that contains a regulatory 5' leader. Possible PERK effectors other than ATF4 remain poorly understood. Here, we report that the bZIP transcription factor Xrp1 is required for ATF4-independent PERK signaling. Cell-type-specific gene expression profiling in Drosophila indicated that delta-family glutathione-S-transferases (gstD) are prominently induced by the UPR-activating transgene Rh1G69D. Perk was necessary and sufficient for such gstD induction, but ATF4 was not required. Instead, Perk and other regulators of eIF2α phosphorylation regulated Xrp1 protein levels to induce gstDs. The Xrp1 5' leader has a conserved upstream Open Reading Frame (uORF) analogous to those that regulate ATF4 translation. The gstD-GFP reporter induction required putative Xrp1 binding sites. These results indicate that antioxidant genes are highly induced by a previously unrecognized UPR signaling axis consisting of PERK and Xrp1.


Assuntos
Antioxidantes/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/enzimologia , Glutationa Transferase/metabolismo , Discos Imaginais/enzimologia , eIF-2 Quinase/metabolismo , Animais , Animais Geneticamente Modificados , Sítios de Ligação , Proteínas de Ligação a DNA/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/embriologia , Drosophila melanogaster/genética , Estresse do Retículo Endoplasmático , Fator de Iniciação 2 em Eucariotos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Glutationa Transferase/genética , Discos Imaginais/embriologia , Fases de Leitura Aberta , Fosforilação , Rodopsina/genética , Rodopsina/metabolismo , Transdução de Sinais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Resposta a Proteínas não Dobradas , eIF-2 Quinase/genética
13.
Elife ; 102021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34636720

RESUMO

Associative learning allows animals to use past experience to predict future events. The circuits underlying memory formation support immediate and sustained changes in function, often in response to a single example. Larval Drosophila is a genetic model for memory formation that can be accessed at molecular, synaptic, cellular, and circuit levels, often simultaneously, but existing behavioral assays for larval learning and memory do not address individual animals, and it has been difficult to form long-lasting memories, especially those requiring synaptic reorganization. We demonstrate a new assay for learning and memory capable of tracking the changing preferences of individual larvae. We use this assay to explore how activation of a pair of reward neurons changes the response to the innately aversive gas carbon dioxide (CO2). We confirm that when coupled to CO2 presentation in appropriate temporal sequence, optogenetic reward reduces avoidance of CO2. We find that learning is switch-like: all-or-none and quantized in two states. Memories can be extinguished by repeated unrewarded exposure to CO2 but are stabilized against extinction by repeated training or overnight consolidation. Finally, we demonstrate long-lasting protein synthesis dependent and independent memory formation.


Assuntos
Aprendizagem por Associação , Aprendizagem da Esquiva , Comportamento Animal , Drosophila melanogaster/fisiologia , Memória , Animais , Animais Geneticamente Modificados , Dióxido de Carbono , Proteínas de Drosophila/biossíntese , Proteínas de Drosophila/genética , Drosophila melanogaster/embriologia , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Extinção Psicológica , Larva/genética , Larva/metabolismo , Larva/fisiologia , Odorantes , Percepção Olfatória , Optogenética , Recompensa , Olfato , Fatores de Tempo
14.
Int J Mol Sci ; 22(19)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34638786

RESUMO

Alzheimer's disease is a widespread and devastating neurological disorder associated with proteotoxic events caused by the misfolding and aggregation of the amyloid-ß peptide. To find therapeutic strategies to combat this disease, Drosophila melanogaster has proved to be an excellent model organism that is able to uncover anti-proteotoxic candidates due to its outstanding genetic toolbox and resemblance to human disease genes. In this review, we highlight the use of Drosophila melanogaster to both study the proteotoxicity of the amyloid-ß peptide and to screen for drug candidates. Expanding the knowledge of how the etiology of Alzheimer's disease is related to proteotoxicity and how drugs can be used to block disease progression will hopefully shed further light on the field in the search for disease-modifying treatments.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Doença de Alzheimer/genética , Peptídeos beta-Amiloides/genética , Animais , Modelos Animais de Doenças , Drosophila melanogaster , Humanos
15.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638976

RESUMO

Lysosomal degradation, the common destination of autophagy and endocytosis, is one of the most important elements of eukaryotic metabolism. The small GTPases Rab39A and B are potential new effectors of this pathway, as their malfunction is implicated in severe human diseases like cancer and neurodegeneration. In this study, the lysosomal regulatory role of the single Drosophila Rab39 ortholog was characterized, providing valuable insight into the potential cell biological mechanisms mediated by these proteins. Using a de novo CRISPR-generated rab39 mutant, we found no failure in the early steps of endocytosis and autophagy. On the contrary, we found that Rab39 mutant nephrocytes internalize and degrade endocytic cargo at a higher rate compared to control cells. In addition, Rab39 mutant fat body cells contain small yet functional autolysosomes without lysosomal fusion defect. Our data identify Drosophila Rab39 as a negative regulator of lysosomal clearance during both endocytosis and autophagy.


Assuntos
Autofagia/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/enzimologia , Drosophila melanogaster/genética , Endocitose/genética , Lisossomos/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , Animais , Animais Geneticamente Modificados , Sistemas CRISPR-Cas , Proteínas de Drosophila/genética , Larva/enzimologia , Larva/genética , Fenótipo , Proteínas rab de Ligação ao GTP/genética
16.
Phytomedicine ; 93: 153757, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34619431

RESUMO

BACKGROUND: Prolonged maintenance of proteome stability and functionality (proteostasis) is of emerging significance in aging retardation and healthspan. PURPOSE: An enriched polyphenolic extract obtained from the hydrodistillation of rose petals was tested for its capacity to activate the proteostasis network modules, and thus modulate health- and/or lifespan at the cellular and whole organism level. METHODS: The aqueous extract that remained after the hydrodistillation of Rosa damascena petals, was processed with a polystyrene-FPX66 adsorption resin and sequentially fractionated by FCPC. NMR and UHPLC-HRMS analyses revealed the presence of 28 metabolites, mainly glycosides of kaempferol and quercetin. RESULTS: The extract showed high in vitro antioxidant activity and was not toxic in normal human skin fibroblasts, while it promoted the upregulation of NRF2-induced antioxidant genes and main proteostatic modules. Consistently, supplementation of this extract in Drosophila flies' culture medium induced a cncC/NRF2-mediated upregulation of antioxidant and proteostatic modules. Prolonged administration of the extract in flies' culture medium was not toxic and did not affect food intake rate or fecundity; also, it delayed the age-related decline of stress tolerance and locomotion performance (neuromuscular functionality) and dose-dependently extended flies' lifespan. CONCLUSION: Our findings indicate that the enriched polyphenolic extract obtained from the residue of R. damascena hydrodistillation activates cytoprotective cellular modules that, likely, contribute to its potential anti-aging properties.


Assuntos
Rosa , Animais , Antioxidantes/farmacologia , Drosophila melanogaster , Humanos , Longevidade , Proteostase
17.
Nat Commun ; 12(1): 5878, 2021 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620845

RESUMO

Microtubule (MT)-based transport is an evolutionary conserved process finely tuned by posttranslational modifications. Among them, α-tubulin acetylation, primarily catalyzed by a vesicular pool of α-tubulin N-acetyltransferase 1 (Atat1), promotes the recruitment and processivity of molecular motors along MT tracks. However, the mechanism that controls Atat1 activity remains poorly understood. Here, we show that ATP-citrate lyase (Acly) is enriched in vesicles and provide Acetyl-Coenzyme-A (Acetyl-CoA) to Atat1. In addition, we showed that Acly expression is reduced upon loss of Elongator activity, further connecting Elongator to Atat1 in a pathway regulating α-tubulin acetylation and MT-dependent transport in projection neurons, across species. Remarkably, comparable defects occur in fibroblasts from Familial Dysautonomia (FD) patients bearing an autosomal recessive mutation in the gene coding for the Elongator subunit ELP1. Our data may thus shine light on the pathophysiological mechanisms underlying FD.


Assuntos
ATP Citrato (pro-S)-Liase/metabolismo , Transporte Axonal/fisiologia , ATP Citrato (pro-S)-Liase/genética , Acetilcoenzima A/metabolismo , Acetilação , Acetiltransferases/genética , Animais , Transporte Axonal/genética , Drosophila melanogaster , Disautonomia Familiar/metabolismo , Feminino , Fibroblastos/metabolismo , Humanos , Larva , Masculino , Camundongos , Microtúbulos/metabolismo , Processamento de Proteína Pós-Traducional , Tubulina (Proteína)/metabolismo
18.
Elife ; 102021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34664550

RESUMO

Individual animals vary in their behaviors. This is true even when they share the same genotype and were reared in the same environment. Clusters of covarying behaviors constitute behavioral syndromes, and an individual's position along such axes of covariation is a representation of their personality. Despite these conceptual frameworks, the structure of behavioral covariation within a genotype is essentially uncharacterized and its mechanistic origins unknown. Passing hundreds of inbred Drosophila individuals through an experimental pipeline that captured hundreds of behavioral measures, we found sparse but significant correlations among small sets of behaviors. Thus, the space of behavioral variation has many independent dimensions. Manipulating the physiology of the brain, and specific neural populations, altered specific correlations. We also observed that variation in gene expression can predict an individual's position on some behavioral axes. This work represents the first steps in understanding the biological mechanisms determining the structure of behavioral variation within a genotype.


Assuntos
Comportamento Animal , Drosophila melanogaster/genética , Genótipo , Animais
19.
Elife ; 102021 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-34677126

RESUMO

Wolbachia are the most widespread bacterial endosymbionts in animals. Within arthropods, these maternally transmitted bacteria can selfishly hijack host reproductive processes to increase the relative fitness of their transmitting females. One such form of reproductive parasitism called male killing, or the selective killing of infected males, is recapitulated to degrees by transgenic expression of the prophage WO-mediated killing (wmk) gene. Here, we characterize the genotype-phenotype landscape of wmk-induced male killing in D. melanogaster using transgenic expression. While phylogenetically distant wmk homologs induce no sex-ratio bias, closely-related homologs exhibit complex phenotypes spanning no death, male death, or death of all hosts. We demonstrate that alternative start codons, synonymous codons, and notably a single synonymous nucleotide in wmk can ablate killing. These findings reveal previously unrecognized features of transgenic wmk-induced killing and establish new hypotheses for the impacts of post-transcriptional processes in male killing variation. We conclude that synonymous sequence changes are not necessarily silent in nested endosymbiotic interactions with life-or-death consequences.


Assuntos
Proteínas de Bactérias/genética , Drosophila melanogaster/microbiologia , Prófagos/genética , Simbiose , Wolbachia/fisiologia , Animais , Proteínas de Bactérias/metabolismo , Masculino , Microrganismos Geneticamente Modificados/genética , Microrganismos Geneticamente Modificados/fisiologia , Wolbachia/genética
20.
Elife ; 102021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34698017

RESUMO

A key regulator of collective cell migrations, which drive development and cancer metastasis, is substrate stiffness. Increased substrate stiffness promotes migration and is controlled by Myosin. Using Drosophila border cell migration as a model of collective cell migration, we identify, for the first time, that the actin bundling protein Fascin limits Myosin activity in vivo. Loss of Fascin results in: increased activated Myosin on the border cells and their substrate, the nurse cells; decreased border cell Myosin dynamics; and increased nurse cell stiffness as measured by atomic force microscopy. Reducing Myosin restores on-time border cell migration in fascin mutant follicles. Further, Fascin's actin bundling activity is required to limit Myosin activation. Surprisingly, we find that Fascin regulates Myosin activity in the border cells to control nurse cell stiffness to promote migration. Thus, these data shift the paradigm from a substrate stiffness-centric model of regulating migration, to uncover that collectively migrating cells play a critical role in controlling the mechanical properties of their substrate in order to promote their own migration. This understudied means of mechanical regulation of migration is likely conserved across contexts and organisms, as Fascin and Myosin are common regulators of cell migration.


Assuntos
Proteínas de Transporte/genética , Movimento Celular/fisiologia , Drosophila melanogaster/fisiologia , Proteínas dos Microfilamentos/genética , Miosinas/metabolismo , Animais , Proteínas de Transporte/metabolismo , Drosophila melanogaster/genética , Proteínas dos Microfilamentos/metabolismo
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