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1.
Nanoscale ; 16(17): 8504-8513, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38591642

RESUMO

Large negative photoconductance (NPC) of SnO2/TiO2 nanoparticles (NPs) heterostructure has been observed with thin film transistor (TFT) geometry and has been investigated using sub-bandgap light (blue) illumination. This negative photoconduction has been detected both in accumulation and depletion mode operation, which effectively reduces the carrier mobility (µ) of the TFT. Moreover, the threshold voltage (Vth) widely shifted in the positive direction under illumination. The combined effects of the reduction of mobility and Vth shifting led to a faster reduction of On (or Off) state current under illumination. The negative photosensitivity of this system is as high as 3.2 A W-1, which has been rarely reported in the earlier literature. Moreover, the variation of On (or Off) current, µ and Vth shift is linear with low-intensity blue light. This SnO2/TiO2 NP bilayer channel has been deposited on top of an ionic dielectric (Li-Al2O3) that reduces its operating voltage of this TFT within 2 V. Furthermore, the device has achieved a saturation mobility of 0.4 cm2 V-1 s-1 with an on/off ratio of 7.4 × 103 in the dark. An energy band diagram model has been proposed based on the type-II heterostructure formation between SnO2/TiO2 semiconductors to explain this NPC mechanism. According to the energy band diagram model, adsorbed H2O molecules of TiO2 NPs created a depleted layer in the heterostructure that accelerated the recombination process of photo-generated carriers rather than its transport.

2.
Sci Total Environ ; 891: 164488, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37247729

RESUMO

The extensive use of Chlorpyrifos (CP) as insecticide has raised concern to their hazardous impact on human health and ecosystems. Bioremediation has been proved as one of the key eco-compatible method for reducing these environmental toxicants. This study explores and evaluate the effectiveness of a combined process including solar Photo-Fenton process followed by bacterial degradation using Ochrobactrum sp. CPD-03 for effective CP degradation in wastewater. Moreover, the in vivo molecular biotoxicity of CP and degraded CP has been evaluated with embryonic zebrafish. The solar Photo-Fenton treatment showed CP degradation efficiency of ∼42 % in 4 h and ∼92 % in 96 h with combined bacterial degradation process. In vivo biotoxicity analysis showed increased survivability of embryonic zebrafish exposed to CP with CPD-03 in water with lesser morphological abnormalities. The mechanistic molecular analysis showed decreased acetylcholinesterase inhibition and GST activity in embryos exposed to CP with CPD-03 for a lesser apoptosis due to influential intrinsic interaction with metabolic proteins. The study advocated to the use of solar Photo-Fenton process followed by bacterial degradation for an efficient ecological degradation of CP for effective reduction of in vivo biotoxicity.


Assuntos
Clorpirifos , Poluentes Químicos da Água , Animais , Humanos , Clorpirifos/toxicidade , Peixe-Zebra , Eliminação de Resíduos Líquidos/métodos , Ferro , Acetilcolinesterase , Ecossistema , Peróxido de Hidrogênio , Bactérias , Poluentes Químicos da Água/toxicidade , Oxirredução
3.
Langmuir ; 38(51): 16067-16072, 2022 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-36512752

RESUMO

Bi-layer epitaxial graphene (BLG) on 6H-SiC(0001) (EG/SiC) was grown and modified by thermal deposition of the molecular electron acceptor tetrafluoro-tetra cyano quinodimethane (F4-TCNQ). The surface-modified system, F4-TCNQ/EG/SiC, was studied by X-ray photoelectron spectroscopy (XPS) and angle-resolved polarized Raman spectroscopy (ARPRS). XPS results indicate that bonding of deposited F4-TCNQ molecules depends on their concentration. Although bonding through the cyano groups is present at all concentrations, charge transfer from graphene to fluorine is evident only at sub-monolayer concentrations. The corresponding change in bond character is coupled with a change in molecular orientation. Raman spectroscopy not only provides results consistent with the findings from the XPS study but also reveals a significant degree of molecular stacking above the monolayer concentration. Thus, both the variation of the acceptor concentration and the number of graphene layers provide further handles to manipulate charge and doping that may be useful in device applications.

4.
Sensors (Basel) ; 22(23)2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36501795

RESUMO

Autonomous driving and its real-world implementation have been among the most actively studied topics in the past few years. In recent years, this growth has been accelerated by the development of advanced deep learning-based data processing technologies. Moreover, large automakers manufacture vehicles that can achieve partially or fully autonomous driving for driving on real roads. However, self-driving cars are limited to some areas with multi-lane roads, such as highways, and self-driving cars that drive in urban areas or residential complexes are still in the development stage. Among autonomous vehicles for various purposes, this paper focused on the development of autonomous vehicles for garbage collection in residential areas. Since we set the target environment of the vehicle as a residential complex, there is a difference from the target environment of a general autonomous vehicle. Therefore, in this paper, we defined ODD, including vehicle length, speed, and driving conditions for the development vehicle to drive in a residential area. In addition, to recognize the vehicle's surroundings and respond to various situations, it is equipped with various sensors and additional devices that can notify the outside of the vehicle's state or operate it in an emergency. In addition, an autonomous driving system capable of object recognition, lane recognition, route planning, vehicle manipulation, and abnormal situation detection was configured to suit the vehicle hardware and driving environment configured in this way. Finally, by performing autonomous driving in the actual experimental section with the developed vehicle, it was confirmed that the function of autonomous driving in the residential area works appropriately. Moreover, we confirmed that this vehicle would support garbage collection works through the experiment of work efficiency.


Assuntos
Condução de Veículo , Veículos Autônomos , Comércio , Reconhecimento Psicológico , Tecnologia
5.
BMC Genomics ; 23(1): 623, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36042416

RESUMO

The pathophysiological effects of a number of metabolic and age-related disorders can be prevented to some extent by exercise and increased physical activity. However, the molecular mechanisms that contribute to the beneficial effects of muscle activity remain poorly explored. Availability of a fast, inexpensive, and genetically tractable model system for muscle activity and exercise will allow the rapid identification and characterization of molecular mechanisms that mediate the beneficial effects of exercise. Here, we report the development and characterization of an optogenetically-inducible muscle contraction (OMC) model in Drosophila larvae that we used to study acute exercise-like physiological responses. To characterize muscle-specific transcriptional responses to acute exercise, we performed bulk mRNA-sequencing, revealing striking similarities between acute exercise-induced genes in flies and those previously identified in humans. Our larval muscle contraction model opens a path for rapid identification and characterization of exercise-induced factors.


Assuntos
Músculo Esquelético , Condicionamento Físico Animal , Animais , Drosophila/genética , Humanos , Larva/genética , Contração Muscular/fisiologia , Músculo Esquelético/metabolismo
6.
OMICS ; 26(9): 473-488, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36040392

RESUMO

COVID-19 is a systemic disease affecting multiple organ systems and caused by infection with the SARS-CoV-2 virus. Two years into the COVID-19 pandemic and after the introduction of several vaccines, the pandemic continues to evolve in part owing to global inequities in access to preventive and therapeutic measures. We are also witnessing the introduction of antivirals against COVID-19. Against this current background, we review the progress made with nanotechnology-based approaches such as nanoformulations to combat the multiorgan effects of SARS-CoV-2 infection from a systems medicine lens. While nanotechnology has previously been widely utilized in the antiviral research domain, it has not yet received the commensurate interest in the case of COVID-19 pandemic response strategies. Notably, SARS-CoV-2 and nanomaterials are similar in size ranging from 50 to 200 nm. Nanomaterials offer the promise to reduce the side effects of antiviral drugs, codeliver multiple drugs while maintaining stability in the biological milieu, and sustain the release of entrapped drug(s) for a predetermined time period, to name but a few conceivable scenarios, wherein nanotechnology can enable and empower preventive medicine and therapeutic innovations against SARS-CoV-2. We conclude the article by underlining that nanotechnology-based interventions warrant further consideration to enable precision planetary health responses against the COVID-19 pandemic.


Assuntos
COVID-19 , Pandemias , Antivirais/farmacologia , Antivirais/uso terapêutico , Vacinas contra COVID-19 , Humanos , Nanotecnologia , Pandemias/prevenção & controle , SARS-CoV-2
7.
Cureus ; 14(4): e23859, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35530886

RESUMO

Introduction Data are scarce on the hematological and biochemical changes caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in neonates. This study aimed to compare hematological and biochemical parameters in SARS-CoV-2-positive neonates with healthy neonates born to mothers diagnosed with coronavirus disease 2019 (COVID-19) and assess disease severity in both groups. Methodology  This prospective observational study was conducted at a COVID-19 hospital at Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India, from May 1 to November 30, 2020. Forty-eight babies, including 39 inborn and nine outborn, were enrolled in the study after their parents provided written informed consent. Neonates were diagnosed with COVID-19 via nasopharyngeal real-time reverse transcription-polymerase chain reaction testing. The hematological and biochemical parameters of these 48 neonates were recorded and analyzed. Results  SARS-CoV-2-infected neonates had lower hemoglobin, neutrophil to lymphocyte ratio, total white blood cell count, and absolute neutrophil count compared to noninfected babies (p<0.05). All SARS-CoV-2-infected neonates had serum transaminase levels and renal function tests within reference ranges. We saw no significant differences in hematological and biochemical parameters among asymptomatic SARS-CoV-2-infected and noninfected neonates.  Conclusions Hematological and biochemical parameters between asymptomatic SARS-CoV-2-infected and non-infected neonates were similar. The blood count abnormalities found in SARS-CoV-2-infected neonates could be due to other associated neonatal comorbidities. According to our results, asymptomatic SARS-CoV-2-infected newborns need close monitoring rather than a battery of investigation.

8.
Soil Sci Soc Am J ; 85(1): 172-183, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34853488

RESUMO

Phosphorus is an essential nutrient for crops. Precise spatiotemporal application of P fertilizer can improve plant P acquisition and reduce run-off losses of P. Optimizing application would benefit from understanding the dynamics of P release from a fertilizer pellet into bulk soil, which requires space- and time-resolved measurements of P concentration in soil solutions. In this study, we combined microdialysis and X-ray computed tomography to investigate P transport in soil. Microdialysis probes enabled repeated solute sampling from one location with minimal physical disturbance, and their small dimensions permitted spatially resolved monitoring. We observed a rapid initial release of P from the source, producing high dissolved P concentrations within the first 24 h, followed by a decrease in dissolved P over time compatible with adsorption onto soil particles. Soils with greater bulk density (i.e., reduced soil porosity) impeded the P pulse movement, which resulted in a less homogeneous distribution of total P in the soil column at the end of the experiment. The model fit to the data showed that the observed phenomena can be explained by diffusion and adsorption. The results showed that compared with conventional measurement techniques (e.g., suction cups), microdialysis measurements present a less invasive alternative. The time-resolved measurements ultimately highlighted rapid P dynamics that require more attention for improving P use efficiency.

9.
Pediatr Neonatol ; 62(5): 499-505, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34147430

RESUMO

BACKGROUND: Current evidence on vertical transmission of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) and neonatal outcome among exposed newborns is emerging and posing a challenge for preventive interventions. Perinatal transmission to the neonates especially during breastfeeding and rooming in is also relatively unknown. METHODS: This prospective observational study was conducted in Kalinga Institute of Medical Science (KIMS), Odisha state from 1st May to 20th October 2020. A total of 165 neonates born to SARS-CoV-2 infected mothers were enrolled. Real time polymerase chain reaction (RT PCR) testing was done in first 32 neonates in initial 24 h of life. RESULTS: The clinical characteristics of 162 mothers & 165 neonates were analyzed. Mode of delivery was by caesarian section in most (n = 103, 60%) cases. Three (3/32, 9.4%) inborn and 6 outborn neonates were SARS-CoV-2 positive. Thirty-eight (23%) babies needed neonatal intensive care. Clinical characteristics of neonates were meconium-stained amniotic fluid (MSAF [23.63%]), prematurity (16.9%), respiratory distress (10.5%), moderate to severe hypoxic ischemic encephalopathy (3.6%), sepsis (7%) and hyperbilirubinemia (8.7%). Out of 138 stable babies kept on mother side and initiated breast feeding, none of them developed any signs and symptoms attributable to SARS-CoV-2. Five (3%) neonates died in COVID hospital of which one baby was SARS-CoV-2 positive. CONCLUSION: There was an increased rate of incidences of hypoxic ischemic encephalopathy, meconium stained liquor and cesarean section delivery in COVID hospital. We found a possible vertical transmission in 9.4% cases. None of the neonates developed sign and symptoms of SARS-CoV-2 infection during rooming in and breast feeding.


Assuntos
COVID-19 , Complicações Infecciosas na Gravidez , Gestantes/psicologia , Cesárea/estatística & dados numéricos , Feminino , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Masculino , Pandemias , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/virologia , Resultado da Gravidez , RNA Viral , SARS-CoV-2
11.
Comput Biol Med ; 128: 104158, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33301953

RESUMO

The COVID-19 pandemic has affected 215 countries and territories around the world with 60,187,347 coronavirus cases and 17,125,719 currently infected patients confirmed as of the November 25, 2020. Currently, many countries are working on developing new vaccines and therapeutic drugs for this novel virus strain, and a few of them are in different phases of clinical trials. The advancement in high-throughput sequence technologies, along with the application of bioinformatics, offers invaluable knowledge on genomic characterization and molecular pathogenesis of coronaviruses. Recent multi-disciplinary studies using bioinformatics methods like sequence-similarity, phylogenomic, and computational structural biology have provided an in-depth understanding of the molecular and biochemical basis of infection, atomic-level recognition of the viral-host receptor interaction, functional annotation of important viral proteins, and evolutionary divergence across different strains. Additionally, various modern immunoinformatic approaches are also being used to target the most promiscuous antigenic epitopes from the SARS-CoV-2 proteome for accelerating the vaccine development process. In this review, we summarize various important computational tools and databases available for systematic sequence-structural study on coronaviruses. The features of these public resources have been comprehensively discussed, which may help experimental biologists with predictive insights useful for ongoing research efforts to find therapeutics against the infectious COVID-19 disease.


Assuntos
COVID-19/epidemiologia , COVID-19/genética , Biologia Computacional , Pandemias , Proteoma/genética , SARS-CoV-2/genética , Simulação por Computador , Humanos
12.
Elife ; 92020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33107824

RESUMO

PDGF/VEGF ligands regulate a plethora of biological processes in multicellular organisms via autocrine, paracrine, and endocrine mechanisms. We investigated organ-specific metabolic roles of Drosophila PDGF/VEGF-like factors (Pvfs). We combine genetic approaches and single-nuclei sequencing to demonstrate that muscle-derived Pvf1 signals to the Drosophila hepatocyte-like cells/oenocytes to suppress lipid synthesis by activating the Pi3K/Akt1/TOR signaling cascade in the oenocytes. Functionally, this signaling axis regulates expansion of adipose tissue lipid stores in newly eclosed flies. Flies emerge after pupation with limited adipose tissue lipid stores and lipid level is progressively accumulated via lipid synthesis. We find that adult muscle-specific expression of pvf1 increases rapidly during this stage and that muscle-to-oenocyte Pvf1 signaling inhibits expansion of adipose tissue lipid stores as the process reaches completion. Our findings provide the first evidence in a metazoan of a PDGF/VEGF ligand acting as a myokine that regulates systemic lipid homeostasis by activating TOR in hepatocyte-like cells.


Assuntos
Proteínas de Drosophila/metabolismo , Proteínas do Ovo/metabolismo , Hepatócitos/metabolismo , Músculo Esquelético/metabolismo , Obesidade/metabolismo , Transdução de Sinais/fisiologia , Animais , Drosophila melanogaster , Corpo Adiposo/metabolismo
13.
Bioessays ; 40(11): e1800044, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30264417

RESUMO

The Transforming growth factor beta (TGF-ß) family of secreted proteins regulates a variety of key events in normal development and physiology. In mammals, this family, represented by 33 ligands, including TGF-ß, activins, nodal, bone morphogenetic proteins (BMPs), and growth and differentiation factors (GDFs), regulate biological processes as diverse as cell proliferation, differentiation, apoptosis, metabolism, homeostasis, immune response, wound repair, and endocrine functions. In Drosophila, only 7 members of this family are present, with 4 TGF-ß/BMP and 3 TGF-ß/activin ligands. Studies in the fly have illustrated the role of TGF-ß/BMP ligands during embryogenesis and organ patterning, while the TGF-ß/activin ligands have been implicated in the control of wing growth and neuronal functions. In this review, we focus on the emerging roles of Drosophila TGF-ß/activins in inter-organ communication via long-distance regulation, especially in systemic lipid and carbohydrate homeostasis, and discuss findings relevant to metabolic diseases in humans.


Assuntos
Ativinas/metabolismo , Metabolismo dos Carboidratos/fisiologia , Drosophila/metabolismo , Metabolismo dos Lipídeos/fisiologia , Transdução de Sinais/fisiologia , Fator de Crescimento Transformador beta/metabolismo , Ativinas/genética , Animais , Proteínas Morfogenéticas Ósseas/metabolismo
14.
Development ; 145(6)2018 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-29467242

RESUMO

Adult size and fitness are controlled by a combination of genetics and environmental cues. In Drosophila, growth is confined to the larval phase and final body size is impacted by the duration of this phase, which is under neuroendocrine control. The neuropeptide prothoracicotropic hormone (PTTH) has been proposed to play a central role in controlling the length of the larval phase through regulation of ecdysone production, a steroid hormone that initiates larval molting and metamorphosis. Here, we test this by examining the consequences of null mutations in the Ptth gene for Drosophila development. Loss of Ptth causes several developmental defects, including a delay in developmental timing, increase in critical weight, loss of coordination between body and imaginal disc growth, and reduced adult survival in suboptimal environmental conditions such as nutritional deprivation or high population density. These defects are caused by a decrease in ecdysone production associated with altered transcription of ecdysone biosynthetic genes. Therefore, the PTTH signal contributes to coordination between environmental cues and the developmental program to ensure individual fitness and survival.


Assuntos
Adaptação Fisiológica/genética , Plasticidade Celular/fisiologia , Drosophila/crescimento & desenvolvimento , Hormônios de Inseto/fisiologia , Adaptação Fisiológica/fisiologia , Animais , Plasticidade Celular/genética , Sinais (Psicologia) , Drosophila/genética , Drosophila/fisiologia , Proteínas de Drosophila/metabolismo , Ecdisona/biossíntese , Meio Ambiente , Imuno-Histoquímica , Hormônios de Inseto/genética , Larva/metabolismo , Larva/fisiologia , Metamorfose Biológica/fisiologia , Mutagênese , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais
16.
Artigo em Inglês | MEDLINE | ID: mdl-28130362

RESUMO

The transforming growth factor ß (TGF-ß) family signaling pathway is conserved and ubiquitous in animals. In Drosophila, fewer representatives of each signaling component are present compared with vertebrates, simplifying mechanistic study of the pathway. Although there are fewer family members, the TGF-ß family pathway still regulates multiple and diverse functions in Drosophila. In this review, we focus our attention on several of the classic and best-studied functions for TGF-ß family signaling in regulating Drosophila developmental processes such as embryonic and imaginal disc patterning, but we also describe several recently discovered roles in regulating hormonal, physiological, neuronal, innate immunity, and tissue homeostatic processes.


Assuntos
Drosophila/metabolismo , Fator de Crescimento Transformador beta/fisiologia , Animais , Padronização Corporal , Proteínas Morfogenéticas Ósseas/metabolismo , Proteínas Morfogenéticas Ósseas/fisiologia , Drosophila/embriologia , Drosophila/crescimento & desenvolvimento , Discos Imaginais/citologia , Discos Imaginais/metabolismo , Redes e Vias Metabólicas , Modelos Moleculares , Transdução de Sinais , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo
17.
Sci Rep ; 5: 13176, 2015 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-26271729

RESUMO

Uracil phosphoribosyltransferase (UPRT) is a pyrimidine salvage pathway enzyme that catalyzes the conversion of uracil to uridine monophosphate (UMP). The enzyme is highly conserved from prokaryotes to humans and yet phylogenetic evidence suggests that UPRT homologues from higher-eukaryotes, including Drosophila, are incapable of binding uracil. Purified human UPRT also do not show any enzymatic activity in vitro, making microbial UPRT an attractive candidate for anti-microbial drug development, suicide-gene therapy, and cell-specific mRNA labeling techniques. Nevertheless, the enzymatic site of UPRT remains conserved across the animal kingdom indicating an in vivo role for the enzyme. We find that the Drosophila UPRT homologue, krishah (kri), codes for an enzyme that is required for larval growth, pre-pupal/pupal viability and long-term adult lifespan. Our findings suggest that UPRT from all higher eukaryotes is likely enzymatically active in vivo and challenges the previous notion that the enzyme is non-essential in higher eukaryotes and cautions against targeting the enzyme for therapeutic purposes. Our findings also suggest that expression of the endogenous UPRT gene will likely cause background incorporation when using microbial UPRT as a cell-specific mRNA labeling reagent in higher eukaryotes.


Assuntos
Envelhecimento/fisiologia , Proteínas de Drosophila/fisiologia , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/metabolismo , Longevidade/fisiologia , Pentosiltransferases/fisiologia , Animais , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Larva/crescimento & desenvolvimento , Larva/metabolismo
18.
Proc Natl Acad Sci U S A ; 112(14): 4195-201, 2015 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-25825777

RESUMO

We examine in Drosophila a group of ∼35 ionotropic receptors (IRs), the IR20a clade, about which remarkably little is known. Of 28 genes analyzed, GAL4 drivers representing 11 showed expression in the larva. Eight drivers labeled neurons of the pharynx, a taste organ, and three labeled neurons of the body wall that may be chemosensory. Expression was not observed in neurons of one taste organ, the terminal organ, although these neurons express many drivers of the Gr (Gustatory receptor) family. For most drivers of the IR20a clade, we observed expression in a single pair of cells in the animal, with limited coexpression, and only a fraction of pharyngeal neurons are labeled. The organization of IR20a clade expression thus appears different from the organization of the Gr family or the Odor receptor (Or) family in the larva. A remarkable feature of the larval pharynx is that some of its organs are incorporated into the adult pharynx, and several drivers of this clade are expressed in the pharynx of both larvae and adults. Different IR drivers show different developmental dynamics across the larval stages, either increasing or decreasing. Among neurons expressing drivers in the pharynx, two projection patterns can be distinguished in the CNS. Neurons exhibiting these two kinds of projection patterns may activate different circuits, possibly signaling the presence of cues with different valence. Taken together, the simplest interpretation of our results is that the IR20a clade encodes a class of larval taste receptors.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila/embriologia , Regulação da Expressão Gênica no Desenvolvimento , Receptores Ionotrópicos de Glutamato/metabolismo , Paladar/fisiologia , Animais , Sistema Nervoso Central/fisiologia , Imuno-Histoquímica , Larva/fisiologia , Neurônios/fisiologia , Faringe/embriologia , Células Receptoras Sensoriais/fisiologia
19.
Proc Natl Acad Sci U S A ; 111(15): 5729-34, 2014 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-24706779

RESUMO

The ability to maintain cellular and physiological metabolic homeostasis is key for the survival of multicellular organisms in changing environmental conditions. However, our understanding of extracellular signaling pathways that modulate metabolic processes remains limited. In this study we show that the Activin-like ligand Dawdle (Daw) is a major regulator of systemic metabolic homeostasis and cellular metabolism in Drosophila. We find that loss of canonical Smad signaling downstream of Daw leads to defects in sugar and systemic pH homeostasis. Although Daw regulates sugar homeostasis by positively influencing insulin release, we find that the effect of Daw on pH balance is independent of its role in insulin signaling and is caused by accumulation of organic acids that are primarily tricarboxylic acid (TCA) cycle intermediates. RNA sequencing reveals that a number of TCA cycle enzymes and nuclear-encoded mitochondrial genes including genes involved in oxidative phosphorylation and ß-oxidation are up-regulated in the daw mutants, indicating either a direct or indirect role of Daw in regulating these genes. These findings establish Activin signaling as a major metabolic regulator and uncover a functional link between TGF-ß signaling, insulin signaling, and metabolism in Drosophila.


Assuntos
Ativinas/metabolismo , Metabolismo dos Carboidratos/fisiologia , Proteínas de Drosophila/deficiência , Drosophila melanogaster/fisiologia , Regulação da Expressão Gênica/fisiologia , Homeostase/fisiologia , Transdução de Sinais/fisiologia , Análise de Variância , Animais , Western Blotting , Proteínas de Transporte , Drosophila melanogaster/metabolismo , Fluorescência , Regulação da Expressão Gênica/genética , Concentração de Íons de Hidrogênio , Larva/crescimento & desenvolvimento , Larva/metabolismo , Reação em Cadeia da Polimerase , Transdução de Sinais/genética
20.
Dev Biol ; 347(2): 271-8, 2010 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-20816678

RESUMO

In Drosophila melanogaster, hypomorphic mutations in the gap gene giant (gt) have long been known to affect ecdysone titers resulting in developmental delay and the production of large (giant) larvae, pupae and adults. However, the mechanism by which gt regulates ecdysone production has remained elusive. Here we show that hypomorphic gt mutations lead to ecdysone deficiency and developmental delay by affecting the specification of the PG neurons that produce prothoracicotropic hormone (PTTH). The gt¹ hypomorphic mutation leads to random loss of PTTH production in one or more of the 4 PG neurons in the larval brain. In cases where PTTH production is lost in all four PG neurons, delayed development and giant larvae are produced. Since immunostaining shows no evidence for Gt expression in the PG neurons once PTTH production is detectable, it is unlikely that Gt directly regulates PTTH expression. Instead, we find that innervation of the prothoracic gland by the PG neurons is absent in gt hypomorphic larvae that do not express PTTH. In addition, PG neuron axon fasciculation is abnormal in many gt hypomorphic larvae. Since several other anteriorly expressed gap genes such as tailless and orthodenticle have previously been found to affect the fate of the cerebral labrum, a region of the brain that gives rise to the neuroendocrine cells that innervate the ring gland, we conclude that gt likely controls ecdysone production indirectly by contributing the peptidergic phenotype of the PTTH-producing neurons in the embryo.


Assuntos
Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Ecdisona/biossíntese , Genes de Insetos , Hormônios de Inseto/biossíntese , Neurônios/metabolismo , Proteínas Repressoras/genética , Animais , Animais Geneticamente Modificados , Axônios/metabolismo , Axônios/ultraestrutura , Padronização Corporal/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crescimento & desenvolvimento , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Masculino , Modelos Neurológicos , Mutação , Neurônios/ultraestrutura , Proteínas Repressoras/metabolismo , Transdução de Sinais
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