RESUMO
Ants communicate via large arrays of pheromones and possess expanded, highly complex olfactory systems, with antennal lobes in the brain comprising up to â¼500 glomeruli. This expansion implies that odors could activate hundreds of glomeruli, which would pose challenges for higher-order processing. To study this problem, we generated transgenic ants expressing the genetically encoded calcium indicator GCaMP in olfactory sensory neurons. Using two-photon imaging, we mapped complete glomerular responses to four ant alarm pheromones. Alarm pheromones robustly activated ≤6 glomeruli, and activity maps for the three pheromones inducing panic alarm in our study species converged on a single glomerulus. These results demonstrate that, rather than using broadly tuned combinatorial encoding, ants employ precise, narrowly tuned, and stereotyped representations of alarm pheromones. The identification of a central sensory hub glomerulus for alarm behavior suggests that a simple neural architecture is sufficient to translate pheromone perception into behavioral outputs.
Assuntos
Formigas , Animais , Formigas/genética , Encéfalo/fisiologia , Odorantes , Feromônios , Olfato/fisiologia , Comportamento AnimalRESUMO
Ants exhibit cooperative behaviors and advanced forms of sociality that depend on pheromone-mediated communication. Odorant receptor neurons (ORNs) express specific odorant receptors (ORs) encoded by a dramatically expanded gene family in ants. In most eusocial insects, only the queen can transmit genetic information, restricting genetic studies. In contrast, workers in Harpegnathos saltator ants can be converted into gamergates (pseudoqueens) that can found entire colonies. This feature facilitated CRISPR-Cas9 generation of germline mutations in orco, the gene that encodes the obligate co-receptor of all ORs. orco mutations should significantly impact olfaction. We demonstrate striking functions of Orco in odorant perception, reproductive physiology, and social behavior plasticity. Surprisingly, unlike in other insects, loss of OR functionality also dramatically impairs development of the antennal lobe to which ORNs project. Therefore, the development of genetics in Harpegnathos establishes this ant species as a model organism to study the complexity of eusociality.
Assuntos
Formigas/crescimento & desenvolvimento , Formigas/genética , Proteínas de Insetos/genética , Receptores Odorantes/genética , Comportamento Social , Sequência de Aminoácidos , Animais , Formigas/anatomia & histologia , Formigas/fisiologia , Antenas de Artrópodes/anatomia & histologia , Antenas de Artrópodes/metabolismo , Sequência de Bases , Comportamento Animal , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Feminino , Técnicas de Inativação de Genes , Proteínas de Insetos/química , Masculino , Mutação , Feromônios/metabolismo , Receptores Odorantes/químicaRESUMO
DNA-PKcs is a key regulator of DNA double-strand break repair. Apart from its canonical role in the DNA damage response, DNA-PKcs is involved in the cellular response to oxidative stress (OS), but its exact role remains unclear. Here, we report that DNA-PKcs-deficient human cells display depolarized mitochondria membrane potential (MMP) and reoriented metabolism, supporting a role for DNA-PKcs in oxidative phosphorylation (OXPHOS). DNA-PKcs directly interacts with mitochondria proteins ANT2 and VDAC2, and formation of the DNA-PKcs/ANT2/VDAC2 (DAV) complex supports optimal exchange of ADP and ATP across mitochondrial membranes to energize the cell via OXPHOS and to maintain MMP. Moreover, we demonstrate that the DAV complex temporarily dissociates in response to oxidative stress to attenuate ADP-ATP exchange, a rate-limiting step for OXPHOS. Finally, we found that dissociation of the DAV complex is mediated by phosphorylation of DNA-PKcs at its Thr2609 cluster by ATM kinase. Based on these findings, we propose that the coordination between the DAV complex and ATM serves as a novel oxidative stress checkpoint to decrease ROS production from mitochondrial OXPHOS and to hasten cellular recovery from OS.
Assuntos
Proteínas Mutadas de Ataxia Telangiectasia , Proteínas de Ligação a DNA , Estresse Oxidativo , Humanos , Trifosfato de Adenosina/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , DNA/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Mitocôndrias/metabolismo , FosforilaçãoRESUMO
Mechanical grasping and holding devices depend upon a firm and controlled grip. The possibility to improve this gripping performance is severely limited by the need for miniaturization in many applications, such as robotics, microassembly, or surgery. In this paper, we show how this gripping can be improved in one application (the endoscopic needle holder) by understanding and imitating the design principles that evolution has selected to make the mandibles of an ant a powerful natural gripping device. State-of-the-art kinematic, morphological, and engineering approaches show that the ant, in contrast to other insects, has considerable movement within the articulation and the jaw´s rotational axis. We derived three major evolutionary design principles from the ant's biting apparatus: 1) a mobile joint axis, 2) a tilted orientation of the mandibular axis, and 3) force transmission of the adductor muscle to the tip of the mandible. Application of these three principles to a commercially available endoscopic needle holder resulted in calculated force amplification up to 296% and an experimentally measured one up to 433%. This reduced the amount of translations and rotations of the needle, compared to the needle's original design, while retaining its size or outer shape. This study serves as just one example showing how bioengineers might find elegant solutions to their design problems by closely observing the natural world.
Assuntos
Formigas , Mandíbula , Animais , Mandíbula/anatomia & histologia , Agulhas , Formigas/fisiologia , Fenômenos BiomecânicosRESUMO
Phosphoglycerate dehydrogenase (PHGDH) is a key serine biosynthesis enzyme whose aberrant expression promotes various types of tumors. Recently, PHGDH has been found to have some non-canonical functions beyond serine biosynthesis, but its specific mechanisms in tumorigenesis remain unclear. Here, we show that PHGDH localizes to the inner mitochondrial membrane and promotes the translation of mitochondrial DNA (mtDNA)-encoded proteins in liver cancer cells. Mechanistically, we demonstrate that mitochondrial PHGDH directly interacts with adenine nucleotide translocase 2 (ANT2) and then recruits mitochondrial elongation factor G2 (mtEFG2) to promote mitochondrial ribosome recycling efficiency, thereby promoting mtDNA-encoded protein expression and subsequent mitochondrial respiration. Moreover, we show that treatment with a mitochondrial translation inhibitor or depletion of mtEFG2 diminishes PHGDH-mediated tumor growth. Collectively, our findings uncover a previously unappreciated function of PHGDH in tumorigenesis acting via promotion of mitochondrial translation and bioenergetics.
Assuntos
Neoplasias Hepáticas , Fosfoglicerato Desidrogenase , Humanos , Fosfoglicerato Desidrogenase/genética , Fosfoglicerato Desidrogenase/metabolismo , Linhagem Celular Tumoral , Serina , Neoplasias Hepáticas/genética , Carcinogênese , DNA MitocondrialRESUMO
Colonies of the arboreal turtle ant create networks of trails that link nests and food sources on the graph formed by branches and vines in the canopy of the tropical forest. Ants put down a volatile pheromone on the edges as they traverse them. At each vertex, the next edge to traverse is chosen using a decision rule based on the current pheromone level. There is a bidirectional flow of ants around the network. In a previous field study, it was observed that the trail networks approximately minimize the number of vertices, thus solving a variant of the popular shortest path problem without any central control and with minimal computational resources. We propose a biologically plausible model, based on a variant of the reinforced random walk on a graph, which explains this observation and suggests surprising algorithms for the shortest path problem and its variants. Through simulations and analysis, we show that when the rate of flow of ants does not change, the dynamics converges to the path with the minimum number of vertices, as observed in the field. The dynamics converges to the shortest path when the rate of flow increases with time, so the colony can solve the shortest path problem merely by increasing the flow rate. We also show that to guarantee convergence to the shortest path, bidirectional flow and a decision rule dividing the flow in proportion to the pheromone level are necessary, but convergence to approximately short paths is possible with other decision rules.
Assuntos
Formigas , Animais , Árvores , Algoritmos , Feromônios , FlorestasRESUMO
Historically, those ecological communities thought to be dominated by competitive interactions among their component species have been assumed to exhibit transitive competition, that is, a hierarchy of competitive strength from most dominant to most submissive. A surge of recent literature takes issue with this assumption and notes that some species in some communities are intransitive, where a rock/scissors/paper arrangement characterizes some components of some communities. We here propose a merging of these two ideas, wherein an intransitive subgroup of species connects with a distinct subcomponent that is organized hierarchically, such that the expected eventual takeover by the dominant competitor in the hierarchy is thwarted, and the entire community can be sustained. This means that the combination of transitive and intransitive structures can maintain many species even when competition is strong. Here, we develop this theoretical framework using a simple variant on the Lotka-Volterra competition equations to illustrate the process. We also present data for the ant community in a coffee agroecosystem in Puerto Rico, that appears to be organized in this way. A detailed study on one typical coffee farm illustrates an intransitive loop of three species that seems to maintain a distinct competitive community of at least 13 additional species.
RESUMO
Chemoresistance is the main obstacle in the clinical treatment of osteosarcoma (OS). In this study, we investigated the role of EF-hand domain-containing protein 1 (EFHD1) in OS chemotherapy resistance. We found that the expression of EFHD1 was highly correlated with the clinical outcome after chemotherapy. We overexpressed EFHD1 in 143B cells and found that it increased their resistance to cell death after drug treatment. Conversely, knockdown of EFHD1 in 143BR cells (a cisplatin-less-sensitive OS cell line derived from 143B cells) increased their sensitivity to treatment. Mechanistically, EFHD1 bound to adenine nucleotide translocase-3 (ANT3) and inhibited its conformational change, thereby inhibiting the opening of the mitochondrial membrane permeability transition pore (mPTP). This effect could maintain mitochondrial function, thereby favoring OS cell survival. The ANT3 conformational inhibitor carboxyatractyloside (CATR), which can promote mPTP opening, enhanced the chemosensitivity of EFHD1-overexpressing cells when combined with cisplatin. The ANT3 conformational inhibitor bongkrekic acid (BKA), which can inhibit mPTP opening, restored the resistance of EFHD1 knockdown cells. In conclusion, our results suggest that EFHD1-ANT3-mPTP might be a promising target for OS therapy in the future.
Assuntos
Proliferação de Células , Cisplatino , Resistencia a Medicamentos Antineoplásicos , Proteínas de Transporte da Membrana Mitocondrial , Poro de Transição de Permeabilidade Mitocondrial , Osteossarcoma , Humanos , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Osteossarcoma/tratamento farmacológico , Osteossarcoma/genética , Poro de Transição de Permeabilidade Mitocondrial/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/genética , Linhagem Celular Tumoral , Cisplatino/farmacologia , Neoplasias Ósseas/patologia , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/genética , Translocador 3 do Nucleotídeo Adenina/metabolismo , Translocador 3 do Nucleotídeo Adenina/genética , Antineoplásicos/farmacologia , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Animais , Camundongos , Ligação ProteicaRESUMO
Adenosine diphosphate (ADP) ribosylation is a reversible posttranslational modification involved in the regulation of numerous cellular processes. Prototype ADP ribosyltransferases (ARTs) from many pathogenic bacteria are known to function as toxins, while other bacterial ARTs have just recently emerged. Recent studies have shown that bacteria also possess enzymes that function as poly-ADP ribose (ADPr) glycohydrolases (PARGs), which reverse poly-ADP ribosylation. However, how bacteria manipulate host target proteins by coordinated reactions of ARTs and ADPr hydrolases (ARHs) remains elusive. The intracellular bacterial pathogen Legionella pneumophila, the causative agent of Legionnaires' disease, transports a large array of effector proteins via the Dot/Icm type IV secretion system to host cells. The effector proteins, which mostly function as enzymes, modulate host cellular processes for the bacteria's benefit. In this study, we identified a pair of L. pneumophila effector proteins, Lpg0080 and Lpg0081, which function as an ART and an ARH, respectively. The two proteins were shown to coordinately modulate mitochondrial ADP/adenosine triphosphate (ATP) translocases (ANTs) by their enzymatic activities to conjugate ADPr to, and remove it from, a key arginine residue. The crystal structures of Lpg0081 and the Lpg0081:ADPr complex indicated that Lpg0081 is a macroD-type ARH with a noncanonical macrodomain, whose folding topology is strikingly distinct from that of the canonical macrodomain that is ubiquitously found in eukaryotic PARGs and ARHs. Our results illustrate that L. pneumophila has acquired an effector pair that coordinately manipulate mitochondrial activity via reversible chemical modification of ANTs.
Assuntos
Legionella pneumophila , Legionella , Difosfato de Adenosina , Trifosfato de Adenosina , Proteínas de Bactérias , Mitocôndrias/fisiologia , Translocases Mitocondriais de ADP e ATPRESUMO
SignificanceInvasive social insects are among the most damaging of invasive organisms and have proved universally intractable to biological control. Despite this, populations of some invasive social insects collapse from unknown causes. We report long-term studies demonstrating that infection by a microsporidian pathogen causes populations of a globally significant invasive ant to collapse to local extinction, providing a mechanistic understanding of a pervasive phenomenon in biological invasions: the collapse of established populations from endogenous factors. We apply this knowledge and successfully eliminate two large, introduced populations of these ants. More broadly, microsporidian pathogens should be evaluated for control of other supercolonial invasive social insects. Diagnosing the cause of unanticipated population collapse in invasive organisms can lead to applied solutions.
Assuntos
Formigas , Microsporídios , Animais , Agentes de Controle Biológico , Espécies Introduzidas , Dinâmica PopulacionalRESUMO
BACKGROUND: Fungi and ants belong to the most important organisms in terrestrial ecosystems on Earth. In nutrient-poor niches of tropical rainforests, they have developed steady ecological relationships as a successful survival strategy. In tropical ant-plant mutualisms worldwide, where resident ants provide the host plants with defense and nutrients in exchange for shelter and food, fungi are regularly found in the ant nesting space, inhabiting ant-made dark-colored piles ("patches"). Unlike the extensively investigated fungus-growing insects, where the fungi serve as the primary food source, the purpose of this ant-fungi association is less clear. To decipher the roles of fungi in these structures within ant nests, it is crucial to first understand the dynamics and drivers that influence fungal patch communities during ant colony development. RESULTS: In this study, we investigated how the ant colony age and the ant-plant species affect the fungal community in the patches. As model we selected one of the most common mutualisms in the Tropics of America, the Azteca-Cecropia complex. By amplicon sequencing of the internal transcribed spacer 2 (ITS2) region, we analyzed the patch fungal communities of 93 Azteca spp. colonies inhabiting Cecropia spp. trees. Our study demonstrates that the fungal diversity in patches increases as the ant colony grows and that a change in the prevalent fungal taxa occurs between initial and established patches. In addition, the ant species significantly influences the composition of the fungal community in established ant colonies, rather than the host plant species. CONCLUSIONS: The fungal patch communities become more complex as the ant colony develops, due to an acquisition of fungi from the environment and a substrate diversification. Our results suggest a successional progression of the fungal communities in the patches during ant colony growth and place the ant colony as the main driver shaping such communities. The findings of this study demonstrate the unexpectedly complex nature of ant-plant mutualisms in tropical regions at a micro scale.
Assuntos
Formigas , Fungos , Micobioma , Simbiose , Formigas/microbiologia , Formigas/fisiologia , Animais , Fungos/genética , Fungos/fisiologia , Fungos/classificação , Cecropia/microbiologia , MirmecófitasRESUMO
BACKGROUND: High-throughput experimental technologies can provide deeper insights into pathway perturbations in biomedical studies. Accordingly, their usage is central to the identification of molecular targets and the subsequent development of suitable treatments for various diseases. Classical interpretations of generated data, such as differential gene expression and pathway analyses, disregard interconnections between studied genes when looking for gene-disease associations. Given that these interconnections are central to cellular processes, there has been a recent interest in incorporating them in such studies. The latter allows the detection of gene modules that underlie complex phenotypes in gene interaction networks. Existing methods either impose radius-based restrictions or freely grow modules at the expense of a statistical bias towards large modules. We propose a heuristic method, inspired by Ant Colony Optimization, to apply gene-level scoring and module identification with distance-based search constraints and penalties, rather than radius-based constraints. RESULTS: We test and compare our results to other approaches using three datasets of different neurodegenerative diseases, namely Alzheimer's, Parkinson's, and Huntington's, over three independent experiments. We report the outcomes of enrichment analyses and concordance of gene-level scores for each disease. Results indicate that the proposed approach generally shows superior stability in comparison to existing methods. It produces stable and meaningful enrichment results in all three datasets which have different case to control proportions and sample sizes. CONCLUSION: The presented network-based gene expression analysis approach successfully identifies dysregulated gene modules associated with a certain disease. Using a heuristic based on Ant Colony Optimization, we perform a distance-based search with no radius constraints. Experimental results support the effectiveness and stability of our method in prioritizing modules of high relevance. Our tool is publicly available at github.com/GhadiElHasbani/ACOxGS.git.
Assuntos
Redes Reguladoras de Genes , Redes Reguladoras de Genes/genética , Humanos , Algoritmos , Doenças Neurodegenerativas/genética , Perfilação da Expressão Gênica/métodos , Biologia Computacional/métodos , Animais , Formigas/genética , Bases de Dados GenéticasRESUMO
Salinity and phosphate (Pi) starvation are the most common abiotic stresses that threaten crop productivity. Salt cress (Eutrema salsugineum) displays good tolerance to both salinity and Pi limitation. Previously, we found several Phosphate Transporter (PHT) genes in salt cress upregulated under salinity. Here, EsPHT1;5 induced by both low Pi (LP) and salinity was further characterized. Overexpression of EsPHT1;5 in salt cress enhanced plant tolerance to LP and salinity, while the knock-down lines exhibited growth retardation. The analysis of phosphorus (P) content and shoot/root ratio of total P in EsPHT1;5-overexpressing salt cress seedlings and the knock-down lines as well as arsenate uptake assays suggested the role of EsPHT1;5 in Pi acquisition and root-shoot translocation under Pi limitation. In addition, overexpression of EsPHT1;5 driven by the native promoter in salt cress enhanced Pi mobilization from rosettes to siliques upon a long-term salt treatment. Particularly, the promoter of EsPHT1;5 outperformed that of AtPHT1;5 in driving gene expression under salinity. We further identified a transcription factor EsANT, which negatively regulated EsPHT1;5 expression and plant tolerance to LP and salinity. Taken together, EsPHT1;5 plays an integral role in Pi acquisition and distribution in plant response to LP and salt stress. Further, EsANT may be involved in the cross-talk between Pi starvation and salinity signaling pathways. This work provides further insight into the mechanism underlying high P use efficiency in salt cress in its natural habitat, and evidence for a link between Pi and salt signaling.
Assuntos
Arabidopsis , Brassicaceae , Brassicaceae/genética , Arabidopsis/genética , Salinidade , Regulação da Expressão Gênica de Plantas , Fosfatos/metabolismo , Raízes de Plantas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
ANT3310 is a novel broad-spectrum diazabicyclooctane serine ß-lactamase inhibitor being developed in combination with meropenem (MEM) for the treatment of serious infections in hospitalized patients where carbapenem-resistant Gram-negative pathogens are expected. In this study, we evaluated the in vitro antibacterial activity of MEM in the presence of ANT3310 at 8 µg/mL against global clinical isolates that included Acinetobacter baumannii (n = 905), carbapenem-resistant Enterobacterales (CRE), carrying either oxacillinase (OXA) (n = 252) or Klebsiella pneumoniae carbapenemase (KPC) (n = 180) carbapenemases, and Pseudomonas aeruginosa (n = 502). MEM was poorly active against A. baumannii, as were MEM-vaborbactam, ceftazidime-avibactam, aztreonam-avibactam, cefepime-taniborbactam, cefepime-zidebactam, and imipenem-relebactam (MIC90 values of ≥32 µg/mL). On the other hand, MEM-ANT3310 displayed an MIC90 value of 4 µg/mL, similar to that observed with sulbactam-durlobactam, a drug developed to specifically treat A. baumannii infections. ANT3310 (8 µg/mL) additionally restored the activity of MEM against OXA- and KPC-producing CREs decreasing MEM MIC90 values from >32 µg/mL to 0.25 and 0.5 µg/mL, respectively. The combination of 8 µg/mL of both MEM and ANT3310 prevented growth of 97.5% of A. baumannii and 100% of OXA- and KPC-positive CREs, with ~90% of P. aeruginosa isolates also displaying MEM MICs ≤8 µg/mL. Furthermore, MEM-ANT3310 was efficacious in both thigh and lung murine infection models with OXA-23 A. baumannii. This study demonstrates the potent in vitro activity of the MEM-ANT3310 combination against both carbapenem-resistant A. baumannii and Enterobacterales clinical isolates, a key differentiator to other ß-lactam/ß-lactamase combinations.
Assuntos
Acinetobacter baumannii , Inibidores de beta-Lactamases , Humanos , Animais , Camundongos , Meropeném/farmacologia , Inibidores de beta-Lactamases/farmacologia , Lactamas , Antibacterianos/farmacologia , beta-Lactamases , Carbapenêmicos/farmacologia , Compostos Azabicíclicos/farmacologia , Combinação de Medicamentos , Testes de Sensibilidade MicrobianaRESUMO
Birds and ants are among the most ubiquitous taxa co-occurring in terrestrial ecosystems, but how they mutually interact is almost unknown. Here, the main features of this neglected interaction are synthetized in a systematic literature review. Interaction with ants has been recorded in 1122 bird species (11.2% of extant species) belonging to 131 families widely distributed across the globe and the avian phylogeny. On the other hand, 47 genus of ants (14.4% of extant genus) belonging to eight subfamilies interact with birds. Interactions include competition, antagonism (either ant-bird mutual predation or parasitism) and living together commensally or mutualistically. Competition (48.9%) and antagonism (36.1%) were the most common reported interactions. The potential for engaging in commensalism and competition with ants has a phylogenetic structure in birds and was present in the birds' ancestor. Interaction is better studied in the tropics, in where the network is less dense and more nested than in temperate or arid biomes. This review demonstrates that ant-bird interactions are a pervasive phenomenon across ecological domains, playing a key role in ecosystem function. Future studies need to combine sensible experimentation within anthropogenic disturbance gradients in order to achieve a better understanding of this interaction.
Assuntos
Formigas , Ecossistema , Animais , Evolução Biológica , Aves , FilogeniaRESUMO
Obligatory ant-plant symbioses often appear to be single evolutionary shifts within particular ant lineages; however, convergence can be revealed once natural history observations are complemented with molecular phylogenetics. Here, we describe a remarkable example of convergent evolution in an ant-plant symbiotic system. Exclusively arboreal, Myrmelachista species can be generalized opportunists nesting in several plant species or obligately symbiotic, live-stem nesters of a narrow set of plant species. Instances of specialization within Myrmelachista are known from northern South America and throughout Middle America. In Middle America, a diverse radiation of specialists occupies understory treelets of lowland rainforests. The morphological and behavioural uniformity of specialists suggests that they form a monophyletic assemblage, diversifying after a single origin of specialization. Using ultraconserved element phylogenomics and ancestral state reconstructions, we show that shifts from opportunistic to obligately symbiotic evolved independently in South and Middle America. Furthermore, our analyses support a remarkable case of convergence within the Middle American radiation, with two independently evolved specialist clades, arising nearly simultaneously from putative opportunistic ancestors during the late Pliocene. This repeated evolution of a complex phenotype suggests similar mechanisms behind trait shifts from opportunists to specialists, generating further questions about the selective forces driving specialization.
Assuntos
Formigas , Evolução Biológica , Filogenia , Simbiose , Formigas/fisiologia , Formigas/genética , Animais , América do Sul , América Central , MirmecófitasRESUMO
BACKGROUND: Angiopoietin-like protein 3 (ANGPTL3) is secreted by hepatocytes and inhibits lipoprotein lipase and endothelial lipase activity. Previous studies reported the correlation between plasma ANGPTL3 levels and high-density lipoprotein (HDL). Recently ANGPTL3 was found to preferentially bind to HDL in healthy human circulation. Here, we examined whether ANGPTL3, as a component of HDL, modulates HDL function and affects HDL other components in human and mice with non-diabetes or type 2 diabetes mellitus. METHODS: HDL was isolated from the plasma of female non-diabetic subjects and type-2 diabetic mellitus (T2DM) patients. Immunoprecipitation, western blot, and ELISA assays were used to examine ANGPTL3 levels in HDL. Db/m and db/db mice, AAV virus mediated ANGPTL3 overexpression and knockdown models and ANGPTL3 knockout mice were used. The cholesterol efflux capacity induced by HDL was analyzed in macrophages preloaded with fluorescent cholesterol. The anti-inflammation capacity of HDL was assessed using flow cytometry to measure VCAM-1 and ICAM-1 expression levels in TNF-α-stimulated endothelial cells pretreated with HDL. RESULTS: ANGPTL3 was found to bind to HDL and be a component of HDL in both non-diabetic subjects and T2DM patients. Flag-ANGPTL3 was found in the HDL of transgenic mice overexpressing Flag-ANGPTL3. ANGPLT3 of HDL was positively associated with cholesterol efflux in female non-diabetic controls (r = 0.4102, p = 0.0117) but not in female T2DM patients (r = - 0.1725, p = 0.3224). Lower ANGPTL3 levels of HDL were found in diabetic (db/db) mice compared to control (db/m) mice and were associated with reduced cholesterol efflux and inhibition of VCAM-1 and ICAM-1 expression in endothelial cells (p < 0.05 for all). Following AAV-mediated ANGPTL3 cDNA transfer in db/db mice, ANGPTL3 levels were found to be increased in HDL, and corresponded to increased cholesterol efflux and decreased ICAM-1 expression. In contrast, knockdown of ANGPTL3 levels in HDL by AAV-mediated shRNA transfer led to a reduction in HDL function (p < 0.05 for both). Plasma total cholesterol, total triglycerides, HDL-c, protein components of HDL and the cholesterol efflux function of HDL were lower in ANGPTL3-/- mice than ANGPTL3+/+ mice, suggesting that ANGPTL3 in HDL may regulate HDL function by disrupting the balance of protein components in HDL. CONCLUSION: ANGPTL3 was identified as a component of HDL in humans and mice. ANGPTL3 of HDL regulated cholesterol efflux and the anti-inflammatory functions of HDL in T2DM mice. Both the protein components of HDL and cholesterol efflux capacity of HDL were decreased in ANGPTL3-/- mice. Our findings suggest that ANGPTL3 in HDL may regulate HDL function by disrupting the balance of protein components in HDL. Our study contributes to a more comprehensive understanding of the role of ANGPTL3 in lipid metabolism.
Assuntos
Proteína 3 Semelhante a Angiopoietina , Diabetes Mellitus Tipo 2 , Animais , Feminino , Humanos , Camundongos , Proteínas Semelhantes a Angiopoietina , Colesterol , Células Endoteliais , Molécula 1 de Adesão Intercelular , Lipoproteínas HDL , Triglicerídeos , Molécula 1 de Adesão de Célula VascularRESUMO
Plants consist of fundamental units of growth called phytomers (leaf or bract, axillary bud, node, and internode), which are repeated and modified throughout shoot development to give plants plasticity for survival and adaptation. One phytomer modification is the suppression or outgrowth of bracts, the leaves subtending the flowers. The floral meristem identity regulator LEAFY (LFY) and the organ boundary genes BLADE-ON-PETIOLE1 (BOP1) and BOP2 have been shown to suppress bract development in Arabidopsis, as mutations in these genes result in bract outgrowth. However, much less is known about the mechanisms that promote bract outgrowth in Arabidopsis mutants such as these. Further understanding of this mechanism may provide a potential tool for modifying leaf development. Here, we showed that the MADS-box genes SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1), FRUITFUL (FUL), and AGAMOUS-LIKE24 (AGL24) play more important roles than BOP1/2 and LFY in bract suppression, and that AINTEGUMENTA (ANT) and the partially redundant AINTEGUMENTA-LIKE6 (AIL6) are necessary for bract outgrowth in these mutant backgrounds. We also demonstrated that misexpression of AIL6 alone is sufficient for bract outgrowth. Our data reveal a mechanism for bract suppression and outgrowth and provide insight into phytomer plasticity.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Flores/crescimento & desenvolvimento , Flores/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Domínio MADS/genética , Proteínas de Domínio MADS/metabolismo , Mutação , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/genética , Folhas de Planta/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genéticaRESUMO
BACKGROUND: Anaphylaxis represents the most severe end of the spectrum of allergic reactions. Frequent elicitors of anaphylaxis are insects, foods, and drugs. This paper summarizes recent development with regard to emerging and novel elicitors of anaphylaxis. SUMMARY: Food allergens on the rise include pulses (like pea, chickpea), seeds (hemp, chia), nuts (cashew), pseudograins (buckwheat, quinoa), fruits, and microalgae. Novel foods are foods that were not consumed to any significant extent in the European Union before May 1997, which includes four edible insects (mealworm, migratory locust, house cricket, and buffalo worm). Recent investigations have pointed out the risk of anaphylaxis associated with the consumption of yellow mealworm for people allergic to shellfish and house dust mites. In Europe, fire ants (mostly Solenopsis invicta) and Vespa velutina nigrithorax represent invasive species, which account for increasing numbers of anaphylactic reactions. Also, several new drugs, especially biologicals, have been associated with anaphylaxis. KEY MESSAGES: Elicitors of anaphylaxis are changing as a result of (i) increase in demand for plant-based food, (ii) introduction of novel foods, (iii) spreading of allergens by climate changes and globalization, or (iv) due to exposure to newly developed drugs.
Assuntos
Alérgenos , Anafilaxia , Hipersensibilidade Alimentar , Anafilaxia/etiologia , Anafilaxia/imunologia , Humanos , Animais , Hipersensibilidade Alimentar/imunologia , Alérgenos/imunologiaRESUMO
Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a widespread invasive procedure for treating drug-resistant epilepsy. Nonetheless, there is a persistent debate regarding the short-term and long-term efficacy and safety of ANT-DBS. Thus we conducted a systematic review and meta-analysis. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we searched PubMed, Cochrane, Embase, and Web of Science for studies treating refractory epilepsy with ANT-DBS. Short-term analysis was considered for studies with a mean follow-up of 3 years or less. The following outcomes were assessed for data extraction: procedure responders and nonresponders, increased seizure frequency, complications, and procedure-related mortality. Of 650 studies, 25 fit our inclusion criteria, involving 427 patients. Previous surgical treatments have been reported in 214 patients (50.1%) and a median average baseline seizure frequency of 64.9 monthly seizures. In the short-term analysis, we observed a proportion of 67% (95% confidence interval [CI] 54%-79%) of responders and 33% (95% CI 21%-46%) of nonresponders. In addition, 4% (95% CI 0%-9%) of the patients presented increased seizure frequency. In the long-term analysis, we observed 72% (95% CI 66%-78%) responders and 27% (95% CI 21%-34%) nonresponders. Moreover, there was a 2% (95% CI 0%-5%) increase in seizure frequency. No procedure-related mortality was reported at any follow-up. ANT-DBS effectively treats refractory epilepsy, with lasting short-term and long-term benefits. It remains safe and efficient despite complications, showing no procedure-linked fatalities, high patient responsiveness, and minimal increased seizures. Consistent results over time and low morbidity/mortality rates emphasize its worth. Further research is necessary to diminish the discrepancy among results.