RESUMO
Finding a mate is of the utmost importance for organisms, and the traits associated with successfully finding one can be under strong selective pressures. In habitats where biomass and population density is often low, like the enormous open spaces of the deep sea, animals have evolved many adaptations for finding mates. One convergent adaptation seen in many deep-sea fishes is sexual dimorphism in olfactory organs, where, relative to body size, males have evolved greatly enlarged olfactory organs compared to females. Females are known to give off chemical cues such as pheromones, and these chemical stimuli can traverse long distances in the stable, stratified water of the deep sea and be picked up by the olfactory organs of males. This adaptation is believed to help males in multiple lineages of fishes find mates in deep-sea habitats. In this study, we describe the first morphological evidence of sexual dimorphism in the olfactory organs of lanternfishes (Myctophidae) in the genus Loweina. Lanternfishes are one of the most abundant vertebrates in the deep sea and are hypothesized to use visual signals from bioluminescence for mate recognition or mate detection. Bioluminescent cues that are readily visible at distances as far as 10 m in the aphotic deep sea are likely important for high population density lanternfish species that have high mate encounter rates. In contrast, myctophids found in lower density environments where species encounter rates are lower, like those in Loweina, likely benefit from longer-range chemical or olfactory cues for finding and identifying mates.
Assuntos
Peixes , Caracteres Sexuais , Animais , Feminino , Masculino , Peixes/anatomia & histologia , EcossistemaRESUMO
Extreme abiotic factors in deep-sea environments, such as near-freezing temperatures, low light, and high hydrostatic pressure, drive the evolution of adaptations that allow organisms to survive under these conditions. Pelagic and benthopelagic fishes that have invaded the deep sea face physiological challenges from increased compression of gasses at depth, which limits the use of gas cavities as a buoyancy aid. One adaptation observed in deep-sea fishes to increase buoyancy is a decrease of high-density tissues. In this study, we analyze mineralization of high-density skeletal tissue in rattails (family Macrouridae), a group of widespread benthopelagic fishes that occur from surface waters to greater than 7000 m depth. We test the hypothesis that rattail species decrease bone density with increasing habitat depth as an adaptation to maintaining buoyancy while living under high hydrostatic pressures. We performed micro-computed tomography (micro-CT) scans on 15 species and 20 specimens of rattails and included two standards of known hydroxyapatite concentration (phantoms) to approximate voxel brightness to bone density. Bone density was compared across four bones (eleventh vertebra, lower jaw, pelvic girdle, and first dorsal-fin pterygiophore). On average, the lower jaw was significantly denser than the other bones. We found no correlation between bone density and depth or between bone density and phylogenetic relationships. Instead, we observed that bone density increases with increasing specimen length within and between species. This study adds to the growing body of work that suggests bone density can increase with growth in fishes, and that bone density does not vary in a straightforward way with depth.
RESUMO
Human populations have been shaped by catastrophes that may have left long-lasting signatures in their genomes. One notable example is the second plague pandemic that entered Europe in ca. 1,347 CE and repeatedly returned for over 300 years, with typical village and town mortality estimated at 10%-40%.1 It is assumed that this high mortality affected the gene pools of these populations. First, local population crashes reduced genetic diversity. Second, a change in frequency is expected for sequence variants that may have affected survival or susceptibility to the etiologic agent (Yersinia pestis).2 Third, mass mortality might alter the local gene pools through its impact on subsequent migration patterns. We explored these factors using the Norwegian city of Trondheim as a model, by sequencing 54 genomes spanning three time periods: (1) prior to the plague striking Trondheim in 1,349 CE, (2) the 17th-19th century, and (3) the present. We find that the pandemic period shaped the gene pool by reducing long distance immigration, in particular from the British Isles, and inducing a bottleneck that reduced genetic diversity. Although we also observe an excess of large FST values at multiple loci in the genome, these are shaped by reference biases introduced by mapping our relatively low genome coverage degraded DNA to the reference genome. This implies that attempts to detect selection using ancient DNA (aDNA) datasets that vary by read length and depth of sequencing coverage may be particularly challenging until methods have been developed to account for the impact of differential reference bias on test statistics.
Assuntos
Peste , Humanos , Peste/epidemiologia , Peste/genética , Pandemias/história , Metagenômica , Genoma Bacteriano , FilogeniaRESUMO
BACKGROUND: Rods and cones are photoreceptor neurons in the retina that are required for visual sensation in vertebrates, wherein the perception of vision is initiated when these neurons respond to photons in the light stimuli. The photoreceptor cell is structurally studied as outer segments (OS) and inner segments (IS) where proper protein sorting, localization, and compartmentalization are critical for phototransduction, visual function, and survival. In human retinal diseases, improper protein transport to the OS or mislocalization of proteins to the IS and other cellular compartments could lead to impaired visual responses and photoreceptor cell degeneration that ultimately cause loss of visual function. RESULTS: Therefore, studying and identifying mechanisms involved in facilitating and maintaining proper protein transport in photoreceptor cells would help our understanding of pathologies involving retinal cell degeneration in inherited retinal dystrophies, age-related macular degeneration, and Usher Syndrome. CONCLUSIONS: Our mini-review will discuss mechanisms of protein transport within photoreceptors and introduce a novel role for an unconventional motor protein, MYO1C, in actin-based motor transport of the visual chromophore Rhodopsin to the OS, in support of phototransduction and visual function.
Assuntos
Degeneração Retiniana , Visão Ocular , Animais , Humanos , Transporte Proteico/fisiologia , Retina , Células Fotorreceptoras Retinianas Cones/metabolismo , Células Fotorreceptoras Retinianas Bastonetes/metabolismoRESUMO
Threadfins (Teleostei: Polynemidae) are a group of fishes named for their elongated and threadlike pectoral-fin rays. These fishes are commonly found in the world's tropical and subtropical waters, and are an economically important group for people living in these regions, with more than 100,000 t harvested in recent years. However, we do not have a detailed understanding of polynemid evolutionary history such that these fishes can be monitored, managed and conserved as an important tropical food source. Recent studies hypothesize at least one genus of threadfins is polyphyletic, and no studies have focused on generating a hypothesis of relationship for the Polynemidae using DNA sequences. In this study, we analyse a genomic dataset of ultraconserved-element and mitochondrial loci to construct a phylogeny of the Polynemidae. We recover the threadfins as a clade sister to flatfishes, with the most taxonomically rich genus, Polydactylus, being resolved as polyphyletic. When comparing our dataset to data from previous studies, we find that a few recent broad-scale phylogenies of fishes have incorporated mislabelled, misidentified or chimeric terminals into their analyses, impacting the relationships of threadfins they recover. We highlight these problematic sequences, providing revised identifications based on the data sequenced in this study. We then discuss the intrarelationships of threadfins, highlighting morphological or ecological characters that support the clades we recover.
Assuntos
Evolução Biológica , Linguados , Animais , Peixes , Linguados/genética , Genoma , Genômica , Humanos , FilogeniaRESUMO
Unconventional myosins, linked to deafness, are also proposed to play a role in retinal cell physiology. However, their direct role in photoreceptor function remains unclear. We demonstrate that systemic loss of the unconventional myosin MYO1C in mice, specifically causes rhodopsin mislocalization, leading to impaired visual function. Electroretinogram analysis of Myo1c knockout (Myo1c-KO) mice showed a progressive loss of photoreceptor function. Immunohistochemistry and binding assays demonstrated MYO1C localization to photoreceptor inner and outer segments (OS) and identified a direct interaction of rhodopsin with MYO1C. In Myo1c-KO retinas, rhodopsin mislocalized to rod inner segments (IS) and cell bodies, while cone opsins in OS showed punctate staining. In aged mice, the histological and ultrastructural examination of the phenotype of Myo1c-KO retinas showed progressively shorter photoreceptor OS. These results demonstrate that MYO1C is important for rhodopsin localization to the photoreceptor OS, and for normal visual function.
Assuntos
Proteínas do Olho/metabolismo , Células Fotorreceptoras/metabolismo , Retina/metabolismo , Rodopsina/metabolismo , Animais , Dineínas/genética , Eletrorretinografia/métodos , Camundongos , Fenótipo , Rodopsina/genéticaRESUMO
OBJECTIVE: The potential of brown adipose tissue (BAT) to influence energy homeostasis in animals and humans is encouraging as this tissue can increase fatty acid and glucose utilization to produce heat through uncoupling protein 1 (UCP1), but the actual mechanism of how the cell regulates glucose uptake is not fully understood. Myosin 1c (Myo1c) is an unconventional motor protein involved in several cellular processes, including insulin-mediated glucose uptake via GLUT4 vesicle fusion in white adipocytes, but its role in glucose uptake in BAT has not previously been investigated. METHODS: Using the specific inhibitor pentachloropseudilin (PClP), a neutralizing antibody assay, and siRNA, we examined the role of Myo1c in mechanisms leading to glucose uptake both in vitro in isolated mouse primary adipocytes and in vivo in mice. RESULTS: Our results show that inhibition of Myo1c removes insulin-stimulated glucose uptake in white adipocytes, while inducing glucose uptake in brown adipocytes, independent of GLUT4, by increasing the expression, translation, and translocation of GLUT1 to the plasma membrane. Inhibition of Myo1c leads to the activation of PKA and downstream substrates p38 and ATF-2, which are known to be involved in the expression of ß-adrenergic genes. CONCLUSIONS: Myo1c is a PKA repressor and regulates glucose uptake into BAT.
Assuntos
Adipócitos Marrons/metabolismo , Glucose/metabolismo , Miosina Tipo I/metabolismo , Animais , Células Cultivadas , Masculino , CamundongosRESUMO
Invadosomes support cell invasion by coupling both acto-adhesive and extracellular matrix degradative functions, which are apparently antagonistic. ß1-integrin dynamics regulate this coupling, but the actual sensing mechanism and effectors involved have not yet been elucidated. Using genetic and reverse genetic approaches combined with biochemical and imaging techniques, we now show that the calcium channel TRPV4 colocalizes with ß1-integrins at the invadosome periphery and regulates its activation and the coupling of acto-adhesive and degradative functions. TRPV4-mediated regulation of podosome function depends on its ability to sense reactive oxygen species (ROS) in invadosomes' microenvironment and involves activation of the ROS/calcium-sensitive kinase Ask1 and binding of the motor MYO1C. Furthermore, disease-associated TRPV4 gain-of-function mutations that modulate ECM degradation are also implicated in the ROS response, which provides new perspectives in our understanding of the pathophysiology of TRPV4 channelopathies.
Assuntos
Podossomos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Canais de Cátion TRPV/metabolismo , Actinas/metabolismo , Animais , Cálcio/metabolismo , Adesão Celular , Cisteína/metabolismo , Ácido Ditionitrobenzoico , Matriz Extracelular/metabolismo , Células HEK293 , Humanos , Peróxido de Hidrogênio/metabolismo , Integrina beta1/metabolismo , MAP Quinase Quinase Quinase 5/metabolismo , Camundongos , Modelos Biológicos , Miosina Tipo I/metabolismo , Transporte Proteico , Células RAW 264.7RESUMO
The interaction of actin and myosin is essential for cell migration. We have identified kaempferol and pentahalogenated pseudilins as efficient inhibitors of migration of MDA-MB-231 breast adenocarcinoma cells. The compounds were studied with respect to possible effects on myosin-2-ATPase activity. The pentahalogenated pseudilins inhibited the enzyme activity in vitro. Flavonoids showed no effect on enzyme activity. The polymerization dynamics of actin was measured to test whether the integrity of F-actin is essential for the migration of MDA-MB-231 cells. Quercetin and kaempferol depolymerized F-actin with similar efficiencies as found for the pentahalogenated pseudilins, whereas epigallocatechin showed the weakest effect. As the inhibitory effect on cell migration may be caused by a toxic effect, we have performed a cytotoxicity test and, furthermore, investigated the influence of the test compounds on cardiac function in eleutheroembryos of medaka (Oryzias latipes). Compared with the pentahalogenated pseudilins, the cytotoxic and cardiotoxic effects of flavonoids on medaka embryos were found to be moderate.
Assuntos
Actinas/antagonistas & inibidores , Quempferóis/farmacologia , Miosinas/antagonistas & inibidores , Quercetina/farmacologia , Actinas/metabolismo , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Quempferóis/química , Estrutura Molecular , Miosinas/metabolismo , Quercetina/química , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
The evolution of heterodonty, the possession of varied tooth morphologies on the jaws of animals, has been relatively unexplored in ray-finned fishes compared to terrestrial vertebrates, and to an even lesser degree in deep-sea fish lineages. Lanternfishes (Myctophiformes) are an abundant and species-rich group endemic to deep-sea pelagic habitats. In this study, we document the presence of heterodonty on the oral jaws of lanternfishes, identifying differing anatomical and positional variations of dentition. We survey the anatomical variation in tooth morphology on the oral jaws of 114 lanternfish species across 37 genera and integrate our findings with a hypothesis of evolutionary relationships of lanternfishes to infer the number of times heterodonty evolved in this lineage. Our results indicate that heterodonty evolved at least six separate times on the oral jaws of lanternfishes, occurring as variable tooth morphologies in combination with villiform teeth. These combinations of tooth types include villiform plus hooked teeth, villiform plus hooked and recurved teeth, villiform plus spade, tricuspid, and hooked teeth, and villiform plus caniniform teeth. The reoccurring evolution of hooked teeth on the premaxilla and dentary in lanternfishes suggests heterodonty may serve an important functional role in their pelagic deep-sea environment. Hooked teeth could aid in securing and retaining prey in the oral cavity and allow for species to specialize on differing food resources, vital attributes for organisms living in open-ocean habitats.
Assuntos
Evolução Biológica , Dentição , Peixes/anatomia & histologia , Animais , Osso e Ossos/anatomia & histologia , Ecossistema , Funções Verossimilhança , Filogenia , Dente/anatomia & histologiaRESUMO
Transforming growth factor-ß (TGF-ß) is known to play a critical role in the pathogenesis of many progressive podocyte diseases. However, the molecular mechanisms regulating TGF-ß signaling in podocytes remain unclear. Using a podocyte-specific myosin (Myo)1c knockout, we demonstrate whether Myo1c is critical for TGF-ß-signaling in podocyte disease pathogenesis. Specifically, podocyte-specific Myo1c knockout mice were resistant to fibrotic injury induced by Adriamycin or nephrotoxic serum. Further, loss of Myo1c also protected from injury in the TGF-ß-dependent unilateral ureteral obstruction mouse model of renal interstitial fibrosis. Mechanistic analyses showed that loss of Myo1c significantly blunted TGF-ß signaling through downregulation of canonical and non-canonical TGF-ß pathways. Interestingly, nuclear rather than the cytoplasmic Myo1c was found to play a central role in controlling TGF-ß signaling through transcriptional regulation. Differential expression analysis of nuclear Myo1c-associated gene promoters showed that nuclear Myo1c targeted the TGF-ß responsive gene growth differentiation factor (GDF)-15 and directly bound to the GDF-15 promoter. Importantly, GDF15 was found to be involved in podocyte pathogenesis, where GDF15 was upregulated in glomeruli of patients with focal segmental glomerulosclerosis. Thus, Myo1c-mediated regulation of TGF-ß-responsive genes is central to the pathogenesis of podocyte injury. Hence, inhibiting this process may have clinical application in treating podocytopathies.
Assuntos
Fator 15 de Diferenciação de Crescimento/genética , Nefropatias/patologia , Miosina Tipo I/metabolismo , Podócitos/patologia , Transdução de Sinais/genética , Fator de Crescimento Transformador beta/metabolismo , Animais , Modelos Animais de Doenças , Doxorrubicina/toxicidade , Feminino , Fibrose , Regulação da Expressão Gênica , Humanos , Nefropatias/induzido quimicamente , Masculino , Camundongos , Camundongos Knockout , Miosina Tipo I/genética , Podócitos/efeitos dos fármacos , Regiões Promotoras Genéticas , Transcrição GênicaRESUMO
Classâ 1 myosins (Myo1s) were the first unconventional myosins identified and humans have eight known Myo1 isoforms. The Myo1 family is involved in the regulation of gene expression, cytoskeletal rearrangements, delivery of proteins to the cell surface, cell migration and spreading. Thus, the important role of Myo1s in different biological processes is evident. In this study, we have investigated the effects of pentachloropseudilin (PClP), a reversible and allosteric potent inhibitor of Myo1s, on angiogenesis. We demonstrated that treatment of cells with PClP promoted a decrease in the number of vessels. The observed inhibition of angiogenesis is likely to be related to the inhibition of cell proliferation, migration and adhesion, as well as to alteration of the actin cytoskeleton pattern, as shown on a PClP-treated HUVEC cell line. Moreover, we also demonstrated that PClP treatment partially prevented the delivery of integrins to the plasma membrane. Finally, we showed that PClP caused DNA strand breaks, which are probably repaired during the cell cycle arrest in the G1 phase. Taken together, our results suggest that Myo1s participate directly in the angiogenesis process.
Assuntos
Citoesqueleto de Actina/efeitos dos fármacos , Inibidores da Angiogênese/farmacologia , Ciclo Celular/efeitos dos fármacos , Hidrocarbonetos Clorados/farmacologia , Integrinas/metabolismo , Pirróis/farmacologia , Inibidores da Angiogênese/toxicidade , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Hidrocarbonetos Clorados/toxicidade , Integrinas/genética , Miosina Tipo I/metabolismo , Pirróis/toxicidade , RNA Mensageiro/metabolismoRESUMO
Successful adaptive behavior requires the learning of associations between stimulus-specific choices and rewarding outcomes. Most research on the mechanisms underlying such processes has focused on subcortical reward-processing regions, in conjunction with frontal circuits. Given the extensive stimulus-specific coding in the sensory cortices, we hypothesized they would play a key role in the learning of stimulus-specific reward associations. We recorded electrical brain activity (using electroencephalogram) during a learning-based decision-making gambling task where, on each trial, participants chose between a face and a house and then received feedback (gain or loss). Within each 20-trial set, either faces or houses were more likely to predict a gain. Results showed that early feedback processing (~200-1200 ms) was independent of the choice made. In contrast, later feedback processing (~1400-1800 ms) was stimulus-specific, reflected by decreased alpha power (reflecting increased cortical activity) over face-selective regions, for winning-vs-losing after a face choice but not after a house choice. Finally, as the reward association was learned in a set, there was an increasingly stronger attentional bias towards the more likely winning stimulus, reflected by increasing attentional orienting-related brain activity and increasing likelihood of choosing that stimulus. These results delineate the processes underlying the updating of stimulus-reward associations during feedback-guided learning, which then guide future attentional allocation and decision-making.
Assuntos
Aprendizagem/fisiologia , Recompensa , Córtex Somatossensorial/fisiologia , Adulto , Atenção , Tomada de Decisões , Eletroencefalografia , Retroalimentação , Feminino , Jogo de Azar , Humanos , Masculino , Adulto JovemRESUMO
Class 1 myosins (Myo1s) were the first unconventional myosins identified and humans have eight known Myo1 isoforms. The Myo1 family is involved in the regulation of gene expression, cytoskeletal rearrangements, delivery of proteins to the cell surface, cell migration and spreading. Thus, the important role of Myo1s in different biological processes is evident. In this study, we have investigated the effects of pentachloropseudilin (PClP), a reversible and allosteric potent inhibitor of Myo1s, on angiogenesis. We demonstrated that treatment of cells with PClP promoted a decrease in the number of vessels. The observed inhibition of angiogenesis is likely to be related to the inhibition of cell proliferation, migration and adhesion, as well as to alteration of the actin cytoskeleton pattern, as shown on a PClP‐treated HUVEC cell line. Moreover, we also demonstrated that PClP treatment partially prevented the delivery of integrins to the plasma membrane. Finally, we showed that PClP caused DNA strand breaks, which are probably repaired during the cell cycle arrest in the G1 phase. Taken together, our results suggest that Myo1s participate directly in the angiogenesis process.
RESUMO
Several contemporary models anticipate that the summation effect is modulated by the similarity between the cues forming a compound. Here, we explore this hypothesis in a series of causal learning experiments. Participants were presented with two visual cues that separately predicted a common outcome and later asked for the outcome predicted by the compound of the two cues. Similarity was varied between groups through changes in shape, spatial position, color, configuration, and rotation. In variance with the predictions of these models, we observed similar and strong levels of summation in both groups across all manipulations of similarity. The effect, however, was significantly reduced by manipulations intended to impact assumptions about the causal independence of the cues forming the compound, but this reduction was independent of stimulus similarity. These results are problematic for similarity-based models and can be more readily explained by rational approaches to causal learning.
Assuntos
Aprendizagem por Associação/fisiologia , Feminino , Humanos , MasculinoRESUMO
Pentabromopseudilin (PBrP) is a marine antibiotic isolated from the marine bacteria Pseudomonas bromoutilis and Alteromonas luteoviolaceus. PBrP exhibits antimicrobial, anti-tumour, and phytotoxic activities. In mammalian cells, PBrP is known to act as a reversible and allosteric inhibitor of myosin Va (MyoVa). In this study, we report that PBrP is a potent inhibitor of transforming growth factor-ß (TGF-ß) activity. PBrP inhibits TGF-ß-stimulated Smad2/3 phosphorylation, plasminogen activator inhibitor-1 (PAI-1) protein production and blocks TGF-ß-induced epithelial-mesenchymal transition in epithelial cells. PBrP inhibits TGF-ß signalling by reducing the cell-surface expression of type II TGF-ß receptor (TßRII) and promotes receptor degradation. Gene silencing approaches suggest that MyoVa plays a crucial role in PBrP-induced TßRII turnover and the subsequent reduction of TGF-ß signalling. Because, TGF-ß signalling is crucial in the regulation of diverse pathophysiological processes such as tissue fibrosis and cancer development, PBrP should be further explored for its therapeutic role in treating fibrotic diseases and cancer.
Assuntos
Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Miosina Tipo V/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Pirróis/farmacologia , Receptores de Fatores de Crescimento Transformadores beta/antagonistas & inibidores , Fator de Crescimento Transformador beta/antagonistas & inibidores , Alteromonas/química , Animais , Linhagem Celular , Relação Dose-Resposta a Droga , Células HEK293 , Células Hep G2 , Humanos , Vison , Estrutura Molecular , Miosina Tipo V/metabolismo , Proteínas Serina-Treonina Quinases/biossíntese , Pseudomonas/química , Pirróis/química , Pirróis/isolamento & purificação , Receptor do Fator de Crescimento Transformador beta Tipo II , Receptores de Fatores de Crescimento Transformadores beta/biossíntese , Relação Estrutura-Atividade , Fator de Crescimento Transformador beta/metabolismoRESUMO
Single-headed myosin 1 has been identified in neurons, but its function in these cells is still unclear. We demonstrate that depletion of myosin 1b (Myo1b), inhibition of its motor activity, or its binding to phosphoinositides impairs the formation of the axon, whereas overexpression of Myo1b increases the number of axon-like structures. Myo1b is associated with growth cones and actin waves, two major contributors to neuronal symmetry breaking. We show that Myo1b controls the dynamics of the growth cones and the anterograde propagation of the actin waves. By coupling the membrane to the actin cytoskeleton, Myo1b regulates the size of the actin network as well as the stability and size of filopodia in the growth cones. Our data provide the first evidence that a myosin 1 plays a major role in neuronal symmetry breaking and argue for a mechanical control of the actin cytoskeleton both in actin waves and in the growth cones by this myosin.
Assuntos
Actinas/metabolismo , Axônios/metabolismo , Cones de Crescimento/metabolismo , Miosina Tipo I/metabolismo , Motivos de Aminoácidos , Animais , Biomarcadores/metabolismo , Diferenciação Celular , Movimento Celular , Células Cultivadas , Cinesinas/metabolismo , Camundongos , Atividade Motora , Miosina Tipo I/química , Neuritos/metabolismo , Fosfatos de Fosfatidilinositol/metabolismo , Pseudópodes/metabolismo , RNA Interferente Pequeno/metabolismoRESUMO
Massive parallel sequencing allows scientists to gather DNA sequences composed of millions of base pairs that can be combined into large datasets and analyzed to infer organismal relationships at a genome-wide scale in non-model organisms. Although the use of these large datasets is becoming more widespread, little to no work has been done in estimating phylogenetic relationships using UCEs in deep-sea fishes. Among deep-sea animals, the 257 species of lanternfishes (Myctophiformes) are among the most important open-ocean lineages, representing half of all mesopelagic vertebrate biomass. With this relative abundance, they are key members of the midwater food web where they feed on smaller invertebrates and fishes in addition to being a primary prey item for other open-ocean animals. Understanding the evolution and relationships of midwater organisms generally, and this dominant group of fishes in particular, is necessary for understanding and preserving the underexplored deep-sea ecosystem. Despite substantial congruence in the evolutionary relationships among deep-sea lanternfishes at higher classification levels in previous studies, the relationships among tribes, genera, and species within Myctophidae often conflict across phylogenetic studies or lack resolution and support. Herein we provide the first genome-scale phylogenetic analysis of lanternfishes, and we integrate these data from across the nuclear genome with additional protein-coding gene sequences and morphological data to further test evolutionary relationships among lanternfishes. Our phylogenetic hypotheses of relationships among lanternfishes are entirely congruent across a diversity of analyses that vary in methods, taxonomic sampling, and data analyzed. Within the Myctophiformes, the Neoscopelidae is inferred to be monophyletic and sister to a monophyletic Myctophidae. The current classification of lanternfishes is incongruent with our phylogenetic tree, so we recommend revisions that retain much of the traditional tribal structure and recognize five subfamilies instead of the traditional two subfamilies. The revised monophyletic taxonomy of myctophids includes the elevation of three former lampanyctine tribes to subfamilies. A restricted Lampanyctinae was recovered sister to Notolychninae. These two clades together were recovered as the sister group to the Gymnoscopelinae. Combined, these three subfamilies were recovered as the sister group to a clade composed of a monophyletic Diaphinae sister to the traditional Myctophinae. Our results corroborate recent multilocus molecular studies that infer a polyphyletic Myctophum in Myctophinae, and a para- or polyphyletic Lampanyctus and Nannobrachium within Lampanyctinae. We resurrect Dasyscopelus and Ctenoscopelus for the independent clades traditionally classified as species of Myctophum, and we place Nannobrachium into the synonymy of Lampanyctus.
Assuntos
Peixes/anatomia & histologia , Peixes/classificação , Genômica , Filogenia , Animais , Sequência de Bases , Ecossistema , Peixes/genética , Funções Verossimilhança , Análise de Sequência de DNARESUMO
Pentachloropseudilin (PClP) is a chlorinated phenylpyrrole compound that was first isolated from Actinoplanes (ATCC33002), and its structure has been confirmed by chemical synthesis. PClP shows broad antimicrobial activity against Gram-negative and Gram-positive bacteria, protozoa, fungi, and yeast. In mammalian cells, PClP is known to act as a reversible and allosteric inhibitor of myosinâ 1c (Myo1c). Herein, we report that PCIP is a potent inhibitor of transforming growth factor-ß (TGF-ß)-stimulated signaling. PCIP inhibits TGF-ß-stimulated Smad2/3 phosphorylation and plasminogen activator inhibitor-1 (PAI-1) promoter activation with an IC50 of 0.1â µm in target cells (A549, HepG2, and Mv1Lu cells). In addition, PCIP attenuates TGF-ß-stimulated expression of vimentin, N-cadherin, and fibronectin and, thus, blocks TGF-ß-induced epithelial to mesenchymal transition (EMT) in these cells. Furthermore, cell-surface labeling and immunoblot analysis indicates that PCIP suppresses TGF-ß-stimulated cellular responses by attenuating cell-surface expression of the typeâ II TGF-ß receptor through accelerating caveolae-mediated internalization followed by primarily lysosome-dependent degradation of the receptor, as demonstrated by sucrose density gradient analysis and immune fluorescence staining.
Assuntos
Hidrocarbonetos Clorados/farmacologia , Pirróis/farmacologia , Receptor do Fator de Crescimento Transformador beta Tipo II/agonistas , Fator de Crescimento Transformador beta/efeitos dos fármacos , Animais , Linhagem Celular , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Humanos , Miosina Tipo I/genética , Miosina Tipo I/metabolismo , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
Radiolabeled tracers targeting the prostate-specific membrane antigen (PSMA) have become important radiopharmaceuticals for the PET-imaging of prostate cancer. In this connection, we recently developed the fluorine-18-labelled PSMA-ligand [18F]PSMA-1007 as the next generation radiofluorinated Glu-ureido PSMA inhibitor after [18F]DCFPyL and [18F]DCFBC. Since radiosynthesis so far has been suffering from rather poor yields, novel procedures for the automated radiosyntheses of [18F]PSMA-1007 have been developed. We herein report on both the two-step and the novel one-step procedures, which have been performed on different commonly-used radiosynthesisers. Using the novel one-step procedure, the [18F]PSMA-1007 was produced in good radiochemical yields ranging from 25 to 80% and synthesis times of less than 55 min. Furthermore, upscaling to product activities up to 50 GBq per batch was successfully conducted. All batches passed quality control according to European Pharmacopoeia standards. Therefore, we were able to disclose a new, simple and, at the same time, high yielding production pathway for the next generation PSMA radioligand [18F]PSMA-1007. Actually, it turned out that the radiosynthesis is as easily realised as the well-known [18F]FDG synthesis and, thus, transferable to all currently-available radiosynthesisers. Using the new procedures, the clinical daily routine can be sustainably supported in-house even in larger hospitals by a single production batch.