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1.
Ann Plast Surg ; 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39150845

RESUMO

INTRODUCTION: The deep inferior epigastric perforator (DIEP) flap is currently one of the main options in breast reconstruction. The information about this surgery is critical for the patient, in order to choose the breast reconstruction method. Our study aims to analyze and compare the quality and accuracy of the information related to the DIEP flap reconstruction method provided by social media platforms (SMPs) and the new large language models (LLMs). MATERIALS AND METHODS: A total of 50 videos in English and Spanish were selected from the main SMPs (YouTube, Instagram, and Facebook) using the keywords "DIEP flap" and "colgajo DIEP." The duration, number of likes, dislikes, number of visits, upload date, author, and the video category (institutional video, media, patient experience, academic, and surgery) were analyzed. 3 specific questions were asked to 2 new LLMs (ChatGPT and Google Bard). The quality of information in SMPs and LLMs was analyzed and compared by 2 independent board-certified plastic surgeons using the Journal of American Medical Association and DISCERN scales. RESULTS: LLMs showed a statistically significant higher quality of information when compared with SMPs based on the DISCERN scores. The average DISCERN scores for answers given by ChatGPT and Google Bard were 54 ± 6.841 and 61.17 ± 6.306, respectively (good quality). In SMPs, the average scores were 2.31 ± 0.67 (insufficient quality) and 32.87 ± 9.62 (low quality) for the Journal of American Medical Association and DISCERN scales respectively. Thirty-eight percent of the videos in SMPs were performed by nonmedical authors. CONCLUSIONS: The quality of information for breast reconstruction using DIEP flaps from LLMs was considered good and significantly better than in SMPs. The information found in SMPs was insufficient and of low quality. Academic plastic surgeons have an opportunity to provide quality content on this type of reconstruction in LLM and SMPs.

2.
Int J Mol Sci ; 25(10)2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38791407

RESUMO

Transcription factors (TFs) regulate gene expression by binding to specific sequences on DNA through their DNA-binding domain (DBD), a universal process. This update conveys information about the diverse roles of TFs, focusing on the NACs (NAM-ATAF-CUC), in regulating target-gene expression and influencing various aspects of plant biology. NAC TFs appeared before the emergence of land plants. The NAC family constitutes a diverse group of plant-specific TFs found in mosses, conifers, monocots, and eudicots. This update discusses the evolutionary origins of plant NAC genes/proteins from green algae to their crucial roles in plant development and stress response across various plant species. From mosses and lycophytes to various angiosperms, the number of NAC proteins increases significantly, suggesting a gradual evolution from basal streptophytic green algae. NAC TFs play a critical role in enhancing abiotic stress tolerance, with their function conserved in angiosperms. Furthermore, the modular organization of NACs, their dimeric function, and their localization within cellular compartments contribute to their functional versatility and complexity. While most NAC TFs are nuclear-localized and active, a subset is found in other cellular compartments, indicating inactive forms until specific cues trigger their translocation to the nucleus. Additionally, it highlights their involvement in endoplasmic reticulum (ER) stress-induced programmed cell death (PCD) by activating the vacuolar processing enzyme (VPE) gene. Moreover, this update provides a comprehensive overview of the diverse roles of NAC TFs in plants, including their participation in ER stress responses, leaf senescence (LS), and growth and development. Notably, NACs exhibit correlations with various phytohormones (i.e., ABA, GAs, CK, IAA, JA, and SA), and several NAC genes are inducible by them, influencing a broad spectrum of biological processes. The study of the spatiotemporal expression patterns provides insights into when and where specific NAC genes are active, shedding light on their metabolic contributions. Likewise, this review emphasizes the significance of NAC TFs in transcriptional modules, seed reserve accumulation, and regulation of seed dormancy and germination. Overall, it effectively communicates the intricate and essential functions of NAC TFs in plant biology. Finally, from an evolutionary standpoint, a phylogenetic analysis suggests that it is highly probable that the WRKY family is evolutionarily older than the NAC family.


Assuntos
Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Sementes , Fatores de Transcrição , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Sementes/genética , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Família Multigênica , Evolução Molecular , Estresse Fisiológico , Filogenia , Plantas/genética , Plantas/metabolismo
3.
Int J Mol Sci ; 25(5)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38473843

RESUMO

Gadd45 genes have been implicated in survival mechanisms, including apoptosis, autophagy, cell cycle arrest, and DNA repair, which are processes related to aging and life span. Here, we analyzed if the deletion of Gadd45a activates pathways involved in neurodegenerative disorders such as Alzheimer's Disease (AD). This study used wild-type (WT) and Gadd45a knockout (Gadd45a-/-) mice to evaluate AD progression. Behavioral tests showed that Gadd45a-/- mice presented lower working and spatial memory, pointing out an apparent cognitive impairment compared with WT animals, accompanied by an increase in Tau hyperphosphorylation and the levels of kinases involved in its phosphorylation in the hippocampus. Moreover, Gadd45a-/- animals significantly increased the brain's pro-inflammatory cytokines and modified autophagy markers. Notably, neurotrophins and the dendritic spine length of the neurons were reduced in Gadd45a-/- mice, which could contribute to the cognitive alterations observed in these animals. Overall, these findings demonstrate that the lack of the Gadd45a gene activates several pathways that exacerbate AD pathology, suggesting that promoting this protein's expression or function might be a promising therapeutic strategy to slow down AD progression.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Camundongos , Animais , Doença de Alzheimer/metabolismo , Camundongos Transgênicos , Proteínas tau/metabolismo , Disfunção Cognitiva/metabolismo , Hipocampo/metabolismo , Cognição , Modelos Animais de Doenças
4.
J Med Virol ; 95(2): e28584, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36794675

RESUMO

Novel adjuvants are highly desired to improve immune responses of SARS-CoV-2 vaccines. This work reports the potential of the stimulator of interferon genes (STING) agonist adjuvant, the cyclic di-adenosine monophosphate (c-di-AMP), in a SARS-CoV-2 vaccine based on the receptor binding domain (RBD). Here, mice immunized with two doses of monomeric RBD adjuvanted with c-di-AMP intramuscularly were found to exhibit stronger immune responses compared to mice vaccinated with RBD adjuvanted with aluminum hydroxide (Al(OH)3 ) or without adjuvant. After two immunizations, consistent enhancements in the magnitude of RBD-specific immunoglobulin G (IgG) antibody response were observed by RBD + c-di-AMP (mean: 15360) compared to RBD + Al(OH)3 (mean: 3280) and RBD alone (n.d.). Analysis of IgG subtypes indicated a predominantly Th1-biased immune response (IgG2c, mean: 14480; IgG2b, mean: 1040, IgG1, mean: 470) in mice vaccinated with RBD + c-di-AMP compared to a Th2-biased response in those vaccinated with RBD + Al(OH)3 (IgG2c, mean: 60; IgG2b: n.d.; IgG1, mean: 16660). In addition, the RBD + c-di-AMP group showed better neutralizing antibody responses as determined by pseudovirus neutralization assay and by plaque reduction neutralization assay with SARS-CoV-2 wild type. Moreover, the RBD + c-di-AMP vaccine promoted interferon-γ secretion of spleen cell cultures after RBD stimulation. Furthermore, evaluation of IgG-antibody titers in aged mice showed that di-AMP was able to improve RBD-immunogenicity at old age after 3 doses (mean: 4000). These data suggest that c-di-AMP improves immune responses of a SARS-CoV-2 vaccine based on RBD, and would be considered a promising option for future COVID-19 vaccines.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Animais , Camundongos , Humanos , SARS-CoV-2 , Adjuvantes Imunológicos , Imunidade Celular , Anticorpos Neutralizantes , Adjuvantes Farmacêuticos , Imunoglobulina G , Monofosfato de Adenosina , Anticorpos Antivirais , Glicoproteína da Espícula de Coronavírus , Imunidade Humoral
5.
Cell Commun Signal ; 21(1): 326, 2023 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-37957724

RESUMO

BACKGROUND: The placentas from newborns that are small for gestational age (SGA; birth weight < -2 SD for gestational age) may display multiple pathological characteristics. A key determinant of fetal growth and, therefore, birth weight is placental amino acid transport, which is under the control of the serine/threonine kinase mechanistic target of rapamycin (mTOR). The effects of endoplasmic reticulum (ER) stress on the mTOR pathway and the levels of amino acid transporters are not well established. METHODS: Placentas from SGA and appropriate for gestational age (AGA) newborns and the human placental BeWo cell line exposed to the ER stressor tunicamycin were used. RESULTS: We detected a significant increase in the levels of C/EBP homologous protein (CHOP) in the placentas from SGA newborns compared with those from AGA newborns, while the levels of other ER stress markers were barely affected. In addition, placental mTOR Complex 1 (mTORC1) activity and the levels of the mature form of the amino acid transporter sodium-coupled neutral amino acid transporter 2 (SNAT2) were also reduced in the SGA group. Interestingly, CHOP has been reported to upregulate growth arrest and DNA damage-inducible protein 34 (GADD34), which in turn suppresses mTORC1 activity. The GADD34 inhibitor guanabenz attenuated the increase in CHOP protein levels and the reduction in mTORC1 activity caused by the ER stressor tunicamycin in the human placental cell line BeWo, but it did not recover mature SNAT2 protein levels, which might be reduced as a result of defective glycosylation. CONCLUSIONS: Collectively, these data reveal that GADD34A activity and glycosylation are key factors controlling mTORC1 signaling and mature SNAT2 levels in trophoblasts, respectively, and might contribute to the SGA condition. Video Abstract.


Assuntos
Sistema A de Transporte de Aminoácidos , Placenta , Serina-Treonina Quinases TOR , Fator de Transcrição CHOP , Feminino , Humanos , Recém-Nascido , Gravidez , Peso ao Nascer , Retardo do Crescimento Fetal/genética , Retardo do Crescimento Fetal/metabolismo , Idade Gestacional , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Placenta/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Tunicamicina/farmacologia , Regulação para Cima , Fator de Transcrição CHOP/genética , Sistema A de Transporte de Aminoácidos/genética
6.
Int J Mol Sci ; 24(12)2023 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-37373139

RESUMO

Breast cancer (BC) is a leading cause of cancer-related deaths among women worldwide. Neoadjuvant therapy (NAT) is increasingly being used to reduce tumor burden prior to surgical resection. However, current techniques for assessing tumor response have significant limitations. Additionally, drug resistance is commonly observed, raising a need to identify biomarkers that can predict treatment sensitivity and survival outcomes. Circulating microRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and have been shown to play a significant role in cancer progression as tumor inducers or suppressors. The expression of circulating miRNAs has been found to be significantly altered in breast cancer patients. Moreover, recent studies have suggested that circulating miRNAs can serve as non-invasive biomarkers for predicting response to NAT. Therefore, this review provides a brief overview of recent studies that have demonstrated the potential of circulating miRNAs as biomarkers for predicting the clinical response to NAT in BC patients. The findings of this review will strengthen future research on developing miRNA-based biomarkers and their translation into medical practice, which could significantly improve the clinical management of BC patients undergoing NAT.


Assuntos
Neoplasias da Mama , MicroRNA Circulante , MicroRNAs , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , MicroRNA Circulante/genética , MicroRNA Circulante/uso terapêutico , Terapia Neoadjuvante , Biomarcadores Tumorais/genética , MicroRNAs/metabolismo
7.
Phytother Res ; 36(2): 705-729, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34932245

RESUMO

MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are two main categories of noncoding RNAs (ncRNAs) that can influence essential biological functions in various ways, as well as their expression and function are tightly regulated in physiological homeostasis. Additionally, the dysregulation of these ncRNAs seems to be crucial to the pathogenesis of human diseases. The latest findings indicate that ncRNAs execute vital roles in cancer initiation and progression, and the cancer phenotype can be reversed by modulating their expression. Available scientific discoveries suggest that phytochemicals such as polyphenols, alkaloids, terpenoids, and organosulfur compounds can significantly modulate multiple cancer-associated miRNAs and lncRNAs, thereby inhibiting cancer initiation and development. However, despite promising outcomes of experimental research, only a few clinical trials are currently being conducted to evaluate the therapeutic effectiveness of these compounds. Nevertheless, understanding phytochemical-mediated ncRNA regulation in cancer and the underlying molecular mechanisms on tumor pathophysiology can aid in the development of novel therapeutic strategies to combat this deadly disease.


Assuntos
MicroRNAs , Neoplasias , RNA Longo não Codificante , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/prevenção & controle , Compostos Fitoquímicos/farmacologia , RNA Longo não Codificante/genética
8.
Arch Biochem Biophys ; 699: 108763, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33460581

RESUMO

MicroRNAs (miRNAs) are small non-coding highly conserved RNA molecules that can act as master regulators of gene expression in a sequence-specific manner either by translation repression or mRNA degradation, influencing a wide range of biologic processes that are essential for the maintenance of cellular homeostasis. Chronic pediatric diseases are the leading cause of death worldwide among children and the recent evidence indicates that aberrant miRNA expression significantly contributes to the development of chronic pediatric diseases. This review focuses on the role of miRNAs in five major chronic pediatric diseases including bronchial asthma, congenital heart diseases, cystic fibrosis, type 1 diabetes mellitus, and epilepsy, and their potential use as novel biomarkers for the diagnosis and prognosis of these disorders.


Assuntos
Asma/fisiopatologia , Fibrose Cística/fisiopatologia , Diabetes Mellitus Tipo 1/fisiopatologia , Epilepsia/fisiopatologia , Cardiopatias Congênitas/fisiopatologia , MicroRNAs/fisiologia , Asma/diagnóstico , Asma/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , Doença Crônica , Fibrose Cística/diagnóstico , Fibrose Cística/metabolismo , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/metabolismo , Epilepsia/diagnóstico , Epilepsia/metabolismo , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/metabolismo , Humanos , MicroRNAs/sangue , MicroRNAs/metabolismo , Pediatria , Prognóstico
9.
Small ; 16(16): e1906640, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32187840

RESUMO

Graphene solution-gated field-effect transistors (g-SGFETs) are promising sensing devices to transduce electrochemical potential signals in an electrolyte bath. However, distortion mechanisms in g-SGFET, which can affect signals of large amplitude or high frequency, have not been evaluated. Here, a detailed characterization and modeling of the harmonic distortion and non-ideal frequency response in g-SGFETs is presented. This accurate description of the input-output relation of the g-SGFETs allows to define the voltage- and frequency-dependent transfer functions, which can be used to correct distortions in the transduced signals. The effect of signal distortion and its subsequent calibration are shown for different types of electrophysiological signals, spanning from large amplitude and low frequency cortical spreading depression events to low amplitude and high frequency action potentials. The thorough description of the distortion mechanisms presented in this article demonstrates that g-SGFETs can be used as distortion-free signal transducers not only for neural sensing, but also for a broader range of applications in which g-SGFET sensors are used.


Assuntos
Grafite , Neurônios/fisiologia , Transistores Eletrônicos , Potenciais de Ação , Depressão Alastrante da Atividade Elétrica Cortical
10.
Nat Mater ; 18(3): 280-288, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30598536

RESUMO

Recording infraslow brain signals (<0.1 Hz) with microelectrodes is severely hampered by current microelectrode materials, primarily due to limitations resulting from voltage drift and high electrode impedance. Hence, most recording systems include high-pass filters that solve saturation issues but come hand in hand with loss of physiological and pathological information. In this work, we use flexible epicortical and intracortical arrays of graphene solution-gated field-effect transistors (gSGFETs) to map cortical spreading depression in rats and demonstrate that gSGFETs are able to record, with high fidelity, infraslow signals together with signals in the typical local field potential bandwidth. The wide recording bandwidth results from the direct field-effect coupling of the active transistor, in contrast to standard passive electrodes, as well as from the electrochemical inertness of graphene. Taking advantage of such functionality, we envision broad applications of gSGFET technology for monitoring infraslow brain activity both in research and in the clinic.


Assuntos
Mapeamento Encefálico/instrumentação , Lobo Frontal/fisiologia , Grafite , Microtecnologia/instrumentação , Transistores Eletrônicos , Animais , Grafite/química , Microeletrodos , Modelos Moleculares , Conformação Molecular , Ratos
11.
Pharmacol Res ; 125(Pt B): 224-231, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28918172

RESUMO

Periodontal disease is a frequent chronic inflammatory pathology that implies the destruction of the tissues supporting the teeth, which represents a high sanitary cost. It usually appears associated with other systemic conditions such as diabetes, metabolic syndrome, depression and Alzheimer disease among others. The presence of melatonin and its receptors in the oral cavity supports the hypothesis that this hormone could play a role in homeostasis of periodontal tissues. In the present review we will discuss the potential role of melatonin, a circadian synchronizing hormone, with proved antiinflammatory and antioxidant profile, in the pathogenesis and treatment of periodontitis. Particular emphasis will be placed on the role of the indolamine in the treatment of periodontal disease when this oral condition is comorbid with other pathologies that would also benefit from the therapeutic potential of melatonin and its analogs through diverse mechanisms.


Assuntos
Diabetes Mellitus/metabolismo , Melatonina/metabolismo , Transtornos Mentais/metabolismo , Boca/metabolismo , Doenças Periodontais/metabolismo , Animais , Osso e Ossos/metabolismo , Implantes Dentários , Humanos
12.
Am J Bot ; 104(10): 1556-1568, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-29885219

RESUMO

PREMISE OF THE STUDY: A bird pollination syndrome exists in the Canary Islands archipelago across independent plant lineages despite the absence of specialist birds. The pollination efficiency of current floral visitors remains unknown for many plant species despite this being a fundamental factor in testing hypotheses about the origin of the syndrome. Here, we studied the components of pollination efficiency in the paleoendemic Navaea phoenicea, a species exhibiting conspicuous anatomical modifications associated with bird pollination. METHODS: We measured the components of the pollination efficiency (PE) of species foraging on flowers. The measured quantitative components were visitation frequency patterns to plants and individual flowers. The qualitative components were the contributions to the fitness of male and female functions (pollen removal and deposition and fruit set). KEY RESULTS: Pollination by warbler species was highly efficient, but visit frequency was low; conversely, Canarian chiffchaffs had high visit frequency and low efficiency. Overall PE was almost 0 for blue tits due to disruptive behavior. We also found insects acting as nectar robbers. CONCLUSIONS: Pollination efficiency of three of the four bird species visiting flowers of Navaea phoenicea may be high enough to maintain selective pressure on floral traits of a relict pollination syndrome. The behavior of these birds plays a crucial role in their pollination efficiency. Perching, by generalist passerines when visiting N. phoenicea flowers, is the most efficient habit. The frequency and PE of insect visits calls into question their role as legitimate visitors.


Assuntos
Comportamento Animal , Malvaceae/fisiologia , Passeriformes/fisiologia , Polinização/fisiologia , Animais , Flores/fisiologia , Frutas/fisiologia , Geografia , Néctar de Plantas/fisiologia , Pólen/fisiologia , Espanha
13.
New Phytol ; 210(2): 731-42, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26738752

RESUMO

Hybridization can generate new species if some degree of isolation prevents gene flow between the hybrids and their progenitors. The recruitment of novel pollinators by hybrids has been hypothesized to be one way in which such reproductive isolation can be achieved. We tested whether pollinators contributed to isolation between two natural Narcissus hybrids and their progenitors using pollination experiments, observations, plus morphological and floral-volatile measurements. These hybrids share the same maternal but different paternal progenitors. We found that only the hybrids were visited by and pollinated by ants. The two hybrids exceeded their progenitors in floral-tube aperture size and nectar production. The emission of floral volatiles by hybrid plants was not only equal to or higher than the progenitor species, but also contained some new compounds not produced by the progenitors. The recruitment of ants as novel pollinators in the hybrids involved the combination of increased nectar secretion and the production of novel floral scent compounds. A breakdown of chemical defence against ants may also be involved. This study provides support for the hypothesis that the recruitment of novel pollinators can contribute to reproductive isolation between hybrids and their progenitors.


Assuntos
Insetos/fisiologia , Narcissus/genética , Narcissus/fisiologia , Polinização/fisiologia , Animais , Flores/fisiologia , Frutas/fisiologia , Hibridização Genética , Odorantes , Filogenia , Característica Quantitativa Herdável , Compostos Orgânicos Voláteis/análise
14.
Biol Lett ; 12(4)2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27122008

RESUMO

Pollinator shifts are considered to drive floral trait evolution, yet little is still known about the modifications of petal epidermal surface at a biogeographic region scale. Here we investigated how independent shifts from insects to passerine birds in the Macaronesian Islands consistently modified this floral trait (i.e. absence of papillate cells). Using current phylogenies and extensive evidence from field observations, we selected a total of 81 plant species and subspecies for petal microscopy and comparative analysis, including 19 of the 23 insular species pollinated by opportunistic passerine birds (Macaronesian bird-flowered element). Species relying on passerine birds as the most effective pollinators (bird-pollinated) independently evolved at least five times and in all instances associated with a loss of papillate cells, whereas species with a mixed pollination system (birds plus insects and/or other vertebrates) evolved at least five times in Macaronesia and papillate cells were lost in only 25% of these transitions. Our findings suggest that petal micromorphology is a labile trait during pollinator shifts and that papillate cells tend to be absent on those species where pollinators have limited mechanical interaction with flowers, including opportunistic passerine birds that forage by hovering or from the ground.


Assuntos
Evolução Biológica , Flores/anatomia & histologia , Magnoliopsida/anatomia & histologia , Passeriformes , Epiderme Vegetal/anatomia & histologia , Polinização , Animais , Flores/ultraestrutura , Insetos , Ilhas , Magnoliopsida/ultraestrutura , Filogenia , Epiderme Vegetal/ultraestrutura , Portugal , Espanha
15.
Am J Bot ; 102(6): 833-47, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26101410

RESUMO

PREMISE OF THE STUDY: Phylogenetic and morphological studies have helped clarify the systematics of large and complex groups such as the tribe Crotoneae (Euphorbiaceae). However, very little is known about the diversity, structure, and function of anatomical features in this tribe. Crotoneae comprises the species-rich pantropical genus Croton and six small neotropical genera. Here we characterized the anatomy of leaf secretory structures in members of this tribe and explored their function and evolutionary significance. METHODS: Young and mature leaves of 26 species were studied using standard anatomical light microscopy techniques. Three sections of Croton and one representative of Brasiliocroton and Astraea were sampled. KEY RESULTS: We identified five types of secretory structures: laticifers, colleters, extrafloral nectaries, idioblasts, and secretory trichomes. Laticifers were present in all species studied except Croton alabamensis, which instead presented secretory parenchyma cells. Articulated laticifers are reported in Crotoneae for the first time. Colleters of the standard type were observed in the majority of the sampled taxa. Extrafloral nectaries were present in section Cleodora and in B. mamoninha, but absent in section Lamprocroton and Astraea lobata. Idioblasts were spread throughout the palisade and/or spongy parenchyma in most of the studied species. Secretory trichomes were restricted to Lamprocroton except for C. imbricatus. CONCLUSIONS: This study revealed a high diversity of secretory structures, including novel ones, in one of the largest clades of Euphorbiaceae. Our results are promising for investigations on the anatomical and ecophysiological bases of species diversification within Euphorbiaceae.


Assuntos
Biodiversidade , Evolução Biológica , Euphorbiaceae/anatomia & histologia , Folhas de Planta/anatomia & histologia , Euphorbiaceae/citologia , Filogenia , Folhas de Planta/citologia , Especificidade da Espécie
16.
Phys Rev E ; 109(3-1): 034113, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38632818

RESUMO

This article analyzes and compares two general techniques of rare event simulation for generating paths of Markov processes over fixed time horizons: exponential tilting and stochastic bridge. These two methods allow us to accurately compute the probability that a Markov process ends within a rare region which is unlikely to be attained. Exponential tilting is a general technique for obtaining an alternative or tilted sampling probability measure, under which the Markov process becomes likely to hit the rare region at terminal time. The stochastic bridge technique involves conditioning paths towards two endpoints: the terminal point and the initial one. The terminal point is generated from some appropriately chosen probability distribution that covers well the rare region. We show that both methods belong to the class of importance sampling procedures by providing a common mathematical framework of these two conceptually different methods of sampling rare trajectories. We also conduct a numerical comparison of these two methods, revealing distinct areas of application for each Monte Carlo method, where they exhibit superior efficiency. Detailed simulation algorithms are provided.

17.
Artigo em Inglês | MEDLINE | ID: mdl-38816269

RESUMO

Abnormally increased hepatic gluconeogenesis is a significant contributor to hyperglycemia in the fasting state in patients with type 2 diabetes mellitus (T2DM) due to insulin resistance. Metformin, the most prescribed drug for the treatment of T2DM, is believed to exert its effect mainly by reducing hepatic gluconeogenesis. Here, we discuss how increased hepatic gluconeogenesis contributes to T2DM and we review newly revealed mechanisms underlying the attenuation of gluconeogenesis by metformin. In addition, we analyze the recent findings on new determinants involved in the regulation of gluconeogenesis, which might ultimately lead to the identification of novel and targeted treatment strategies for T2DM.

18.
Metabolism ; 152: 155772, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38176644

RESUMO

INTRODUCTION: The levels of the cellular energy sensor AMP-activated protein kinase (AMPK) have been reported to be decreased via unknown mechanisms in the liver of mice deficient in growth differentiation factor 15 (GDF15). This stress response cytokine regulates energy metabolism mainly by reducing food intake through its hindbrain receptor GFRAL. OBJECTIVE: To examine how GDF15 regulates AMPK. METHODS: Wild-type and Gdf15-/- mice, mouse primary hepatocytes and the human hepatic cell line Huh-7 were used. RESULTS: Gdf15-/- mice showed glucose intolerance, reduced hepatic phosphorylated AMPK levels, increased levels of phosphorylated mothers against decapentaplegic homolog 3 (SMAD3; a mediator of the fibrotic response), elevated serum levels of transforming growth factor (TGF)-ß1, as well as upregulated gluconeogenesis and fibrosis. In line with these observations, recombinant (r)GDF15 promoted AMPK activation and reduced the levels of phosphorylated SMAD3 and the markers of gluconeogenesis and fibrosis in the liver of mice and in mouse primary hepatocytes, suggesting that these effects may be independent of GFRAL. Pharmacological inhibition of SMAD3 phosphorylation in Gdf15-/- mice prevented glucose intolerance, the deactivation of AMPK and the increase in the levels of proteins involved in gluconeogenesis and fibrosis, suggesting that overactivation of the TGF-ß1/SMAD3 pathway is responsible for the metabolic alterations in Gdf15-/- mice. CONCLUSIONS: Overall, these findings indicate that GDF15 activates AMPK and inhibits gluconeogenesis and fibrosis by lowering the activity of the TGF-ß1/SMAD3 pathway.


Assuntos
Intolerância à Glucose , Fator de Crescimento Transformador beta1 , Humanos , Proteínas Quinases Ativadas por AMP/metabolismo , Fibrose , Gluconeogênese , Intolerância à Glucose/metabolismo , Fator 15 de Diferenciação de Crescimento/genética , Fígado/metabolismo , Transdução de Sinais , Proteína Smad3 , Fator de Crescimento Transformador beta1/metabolismo
19.
Ann Bot ; 112(8): 1597-612, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23287557

RESUMO

BACKGROUND AND AIMS: Most of the diversity in the pseudanthia of Asteraceae is based on the differential symmetry and sexuality of its flowers. In Anacyclus, where there are (1) homogamous capitula, with bisexual, mainly actinomorphic and pentamerous flowers; and (2) heterogamous capitula, with peripheral zygomorphic, trimerous and long-/short-rayed female flowers, the floral ontogeny was investigated to infer their origin. METHODS: Floral morphology and ontogeny were studied using scanning electron microscope and light microscope techniques. KEY RESULTS: Disc flowers, subtended by paleae, initiate acropetally. Perianth and androecium initiation is unidirectional/simultaneous. Late zygomorphy occurs by enlargement of the adaxial perianth lobes. In contrast, ray flowers, subtended by involucral bracts, initiate after the proximal disc buds, breaking the inflorescence acropetal pattern. Early zygomorphy is manifested through the fusion of the lateral and abaxial perianth lobes and the arrest of the adaxials. We report atypical phenotypes with peripheral 'trumpet' flowers from natural populations. The peripheral 'trumpet' buds initiate after disc flowers, but maintain an actinomorphic perianth. All phenotypes are compared and interpreted in the context of alternative scenarios for the origin of the capitulum and the perianth identity. CONCLUSIONS: Homogamous inflorescences display a uniform floral morphology and development, whereas the peripheral buds in heterogamous capitula display remarkable plasticity. Disc and ray flowers follow different floral developmental pathways. Peripheral zygomorphic flowers initiate after the proximal actinomorphic disc flowers, behaving as lateral independent units of the pseudanthial disc from inception. The perianth and the androecium are the most variable whorls across the different types of flowers, but their changes are not correlated. Lack of homology between hypanthial appendages and a calyx, and the perianth double-sided structure are discussed for Anacyclus together with potential causes of its ray flower plasticity.


Assuntos
Asteraceae/anatomia & histologia , Asteraceae/crescimento & desenvolvimento , Evolução Biológica , Flores/anatomia & histologia , Flores/crescimento & desenvolvimento , Asteraceae/citologia , Asteraceae/ultraestrutura , Flores/citologia , Flores/ultraestrutura , Inflorescência/anatomia & histologia , Inflorescência/citologia , Inflorescência/crescimento & desenvolvimento , Inflorescência/ultraestrutura , Fenótipo
20.
Am J Bot ; 100(8): 1641-50, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23857736

RESUMO

PREMISE OF THE STUDY: Mountain plants are among the species most vulnerable to global warming, because of their isolation, narrow geographic distribution, and limited geographic range shifts. Stochastic and selective processes can act on the genome, modulating genetic structure and diversity. Fragmentation and historical processes also have a great influence on current genetic patterns, but the spatial and temporal contexts of these processes are poorly known. We aimed to evaluate the microevolutionary processes that may have taken place in Mediterranean high-mountain plants in response to changing historical environmental conditions. METHODS: Genetic structure, diversity, and loci under selection were analyzed using AFLP markers in 17 populations distributed over the whole geographic range of Armeria caespitosa, an endemic plant that inhabits isolated mountains (Sierra de Guadarrama, Spain). Differences in altitude, geographic location, and climate conditions were considered in the analyses, because they may play an important role in selective and stochastic processes. KEY RESULTS: Bayesian clustering approaches identified nine genetic groups, although some discrepancies in assignment were found between alternative analyses. Spatially explicit analyses showed a weak relationship between genetic parameters and spatial or environmental distances. However, a large proportion of outlier loci were detected, and some outliers were related to environmental variables. CONCLUSIONS: A. caespitosa populations exhibit spatial patterns of genetic structure that cannot be explained by the isolation-by-distance model. Shifts along the altitude gradient in response to Pleistocene climatic oscillations and environmentally mediated selective forces might explain the resulting structure and genetic diversity values found.


Assuntos
Variação Genética , Genética Populacional , Genoma de Planta/genética , Plumbaginaceae/genética , Altitude , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Clima , Mudança Climática , Ecossistema , Fluxo Gênico , Loci Gênicos , Estruturas Genéticas , Geografia , Repetições de Microssatélites/genética , Espanha
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