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1.
Plant J ; 114(4): 783-804, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36861314

RESUMO

A level of redundancy and interplay among the transcriptional regulators of floral development safeguards a plant's reproductive success and ensures crop production. In the present study, an additional layer of complexity in the regulation of floral meristem (FM) identity and flower development is elucidated linking carotenoid biosynthesis and metabolism to the regulation of determinate flowering. The accumulation and subsequent cleavage of a diverse array of ζ-carotenes in the chloroplast biogenesis 5 (clb5) mutant of Arabidopsis results in the reprogramming of meristematic gene regulatory networks establishing FM identity mirroring that of the FM identity master regulator, APETALA1 (AP1). The immediate transition to floral development in clb5 requires long photoperiods in a GIGANTEA-independent manner, whereas AP1 is essential for the floral organ development of clb5. The elucidation of this link between carotenoid metabolism and floral development translates to tomato exposing a regulation of FM identity redundant to and initiated by AP1 and proposed to be dependent on the E class floral initiation and organ identity regulator, SEPALLATA3 (SEP3).


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Solanum lycopersicum , Arabidopsis/metabolismo , Solanum lycopersicum/genética , Meristema , Regulação da Expressão Gênica de Plantas , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Carotenoides/metabolismo , Flores
2.
New Phytol ; 2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38922903

RESUMO

The GOLDEN2-LIKE (GLK) transcription factors act as a central regulatory node involved in both developmental processes and environmental responses. Marchantia polymorpha, a basal terrestrial plant with strategic evolutionary position, contains a single GLK representative that possesses an additional domain compared to spermatophytes. We analyzed the role of MpGLK in chloroplast biogenesis and development by altering its levels, preforming transcriptomic profiling and conducting chromatin immunoprecipitation. Decreased MpGLK levels impair chloroplast differentiation and disrupt the expression of photosynthesis-associated nuclear genes, while overexpressing MpGLK leads to ectopic chloroplast biogenesis. This demonstrates the MpGLK functions as a bona fide GLK protein, likely representing an ancestral GLK architecture. Altering MpGLK levels directly regulates the expression of genes involved in Chl synthesis and degradation, similar to processes observed in eudicots, and causes various developmental defects in Marchantia, including the formation of dorsal structures such as air pores and gemma cups. MpGLK, also directly activates MpMAX2 gene expression, regulating the timing of gemma cup development. Our study shows that MpGLK functions as a master regulator, potentially coupling chloroplast development with vegetative reproduction. This illustrates the complex regulatory networks governing chloroplast function and plant development communication and highlight the evolutionary conservation of GLK-mediated regulatory processes across plant species.

3.
Antimicrob Agents Chemother ; 67(4): e0170322, 2023 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-36975844

RESUMO

Antiviral compounds targeting cellular metabolism are part of the therapeutic arsenal to control the spread of virus infection, either as sole treatment or in combination with direct-acting antivirals (DAA) or vaccines. Here, we describe the effect of two of them, lauryl gallate (LG) and valproic acid (VPA) both exhibiting a wide antiviral spectrum, against infection by coronaviruses such as HCoV-229E, HCoV-OC43, and SARS-CoV-2. A consistent 2 to 4-log-decrease in virus yields was observed in the presence of each antiviral, with an average IC50 value of 1.6 µM for LG and 7.2 mM for VPA. Similar levels of inhibition were observed when adding the drug 1 h before adsorption, at the time of infection or 2 h after infection, supporting a postvirus entry mechanism of action. The specificity of the antiviral effect of LG against SARS-CoV-2, relative to other related compounds such as gallic acid (G) and epicatechin gallate (ECG), predicted to be better inhibitors according to in silico studies, was also demonstrated. The combined addition of LG, VPA, and remdesivir (RDV), a DAA with a proven effect against human coronaviruses, resulted in a robust synergistic effect between LG and VPA, and to a lesser extent between the other drug combinations. These findings reinforce the interest of these wide antiviral spectrum host-targeted compounds as a first line of defense against viral diseases or as a vaccine complement to minimize the gap in antibody-mediated protection evoked by vaccines, either in the case of SARS-CoV-2 or for other possible emerging viruses.


Assuntos
COVID-19 , Coronavirus Humano 229E , Coronavirus Humano OC43 , Hepatite C Crônica , Humanos , Antivirais/farmacologia , SARS-CoV-2
4.
J Exp Bot ; 74(8): 2508-2526, 2023 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-36738278

RESUMO

Plastids are a group of essential, heterogenous semi-autonomous organelles characteristic of plants that perform photosynthesis and a diversity of metabolic pathways that impact growth and development. Plastids are remarkably dynamic and can interconvert in response to specific developmental and environmental cues, functioning as a central metabolic hub in plant cells. By far the best studied plastid is the chloroplast, but in recent years the combination of modern techniques and genetic analyses has expanded our current understanding of plastid morphological and functional diversity in both model and non-model plants. These studies have provided evidence of an unexpected diversity of plastid subtypes with specific characteristics. In this review, we describe recent findings that provide insights into the characteristics of these specialized plastids and their functions. We concentrate on the emerging evidence that supports the model that signals derived from particular plastid types play pivotal roles in plant development, environmental, and defense responses. Furthermore, we provide examples of how new technologies are illuminating the functions of these specialized plastids and the overall complexity of their differentiation processes. Finally, we discuss future research directions such as the use of ectopic plastid differentiation as a valuable tool to characterize factors involved in plastid differentiation. Collectively, we highlight important advances in the field that can also impact future agricultural and biotechnological improvement in plants.


Assuntos
Cloroplastos , Plastídeos , Plastídeos/metabolismo , Cloroplastos/metabolismo , Desenvolvimento Vegetal , Plantas/genética , Plantas/metabolismo , Fotossíntese
5.
Reprod Biol Endocrinol ; 21(1): 84, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37700285

RESUMO

BACKGORUND: While various endometrial biomarkers have been characterized at the transcriptomic and functional level, there is generally a poor overlap among studies, making it unclear to what extent their upstream regulators (e.g., ovarian hormones, transcription factors (TFs) and microRNAs (miRNAs)) realistically contribute to menstrual cycle progression and function. Unmasking the intricacies of the molecular interactions in the endometrium from a novel systemic point of view will help gain a more accurate perspective of endometrial regulation and a better explanation the molecular etiology of endometrial-factor infertility. METHODS: An in-silico analysis was carried out to identify which regulators consistently target the gene biomarkers proposed in studies related to endometrial progression and implantation failure (19 gene lists/signatures were included). The roles of these regulators, and of genes related to progesterone and estrogens, were then analysed in transcriptomic datasets compiled from samples collected throughout the menstrual cycle (n = 129), and the expression of selected TFs were prospectively validated in an independent cohort of healthy participants (n = 19). RESULTS: A total of 3,608 distinct genes from the 19 gene lists were associated with endometrial progression and implantation failure. The lists' regulation was significantly favoured by TFs (89% (17/19) of gene lists) and progesterone (47% (8 /19) of gene lists), rather than miRNAs (5% (1/19) of gene lists) or estrogen (0% (0/19) of gene lists), respectively (FDR < 0.05). Exceptionally, two gene lists that were previously associated with implantation failure and unexplained infertility were less hormone-dependent, but primarily regulated by estrogen. Although endometrial progression genes were mainly targeted by hormones rather than non-hormonal contributors (odds ratio = 91.94, FDR < 0.05), we identified 311 TFs and 595 miRNAs not previously associated with ovarian hormones. We highlight CTCF, GATA6, hsa-miR-15a-5p, hsa-miR-218-5p, hsa-miR-107, hsa-miR-103a-3p, and hsa-miR-128-3p, as overlapping novel master regulators of endometrial function. The gene expression changes of selected regulators throughout the menstrual cycle (FDR < 0.05), dually validated in-silico and through endometrial biopsies, corroborated their potential regulatory roles in the endometrium. CONCLUSIONS: This study revealed novel hormonal and non-hormonal regulators and their relative contributions to endometrial progression and pathology, providing new leads for the potential causes of endometrial-factor infertility.


Assuntos
Infertilidade , MicroRNAs , Feminino , Humanos , Transcriptoma , Progesterona , MicroRNAs/genética , Endométrio , Estrogênios
6.
Environ Res ; 233: 116514, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37392826

RESUMO

Cadmium and lead are known to interfere with the endocrine function. Thus, hormonally regulated processes such as menarche, menopause and pregnancy are likely influenced by chronic exposure to these metals. In US post-menopausal women, who already completed their reproductive lifespan, we evaluated the association between blood cadmium and lead levels with self-reported reproductive lifespan and personal history of pregnancy loss. We selected 5317 post-menopausal women participating in the National Health and Nutrition Examination Survey (NHANES), 1999-2018. Blood cadmium and lead levels were measured by inductively coupled plasma mass spectrometry. Reproductive lifespan was defined as the number of years between self-reported age at menarche and menopause. Personal history of pregnancy loss was defined as number of self-reported pregnancy losses out of the self-reported number of pregnancies. The fully adjusted mean difference in reproductive lifespan (95% confidence interval [CI]) comparing the 80th to the 20th percentiles of blood cadmium and lead distributions was, respectively, 0.50 (0.10, 0.91) and 0.72 (0.41, 1.03) years. Ever smoker showed stronger association of blood lead with reproductive lifespan. For self-reported pregnancy loss, the corresponding fully adjusted relative prevalence (95% CI) was 1.10 (0.93, 1.31) for cadmium and 1.10 (1.00, 1.21) for lead, and remained similar after additional adjustment for reproductive lifespan. In never smokers, the relative prevalence was 1.07 (1.04, 1.11) and 1.16 (1.05, 1.28) for blood cadmium and lead, respectively. These findings suggest that blood cadmium and lead exposures increase reproductive lifespan and prevalence of pregnancy loss in the general population. Additional studies are needed to improve the understanding of mechanisms and prevention potential of metals-related pregnancy outcomes.


Assuntos
Aborto Espontâneo , Cádmio , Gravidez , Humanos , Feminino , Inquéritos Nutricionais , Chumbo , Longevidade , Autorrelato , Aborto Espontâneo/induzido quimicamente , Aborto Espontâneo/epidemiologia
7.
Proc Natl Acad Sci U S A ; 117(1): 355-361, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31879352

RESUMO

The methylerythritol phosphate (MEP) pathway is responsible for producing isoprenoids, metabolites with essential functions in the bacterial kingdom and plastid-bearing organisms including plants and Apicomplexa. Additionally, the MEP-pathway intermediate methylerythritol cyclodiphosphate (MEcPP) serves as a plastid-to-nucleus retrograde signal. A suppressor screen of the high MEcPP accumulating mutant plant (ceh1) led to the isolation of 3 revertants (designated Rceh1-3) resulting from independent intragenic substitutions of conserved amino acids in the penultimate MEP-pathway enzyme, hydroxymethylbutenyl diphosphate synthase (HDS). The revertants accumulate varying MEcPP levels, lower than that of ceh1, and exhibit partial or full recovery of MEcPP-mediated phenotypes, including stunted growth and induced expression of stress response genes and the corresponding metabolites. Structural modeling of HDS and ligand docking spatially position the substituted residues at the MEcPP binding pocket and cofactor binding domain of the enzyme. Complementation assays confirm the role of these residues in suppressing the ceh1 mutant phenotypes, albeit to different degrees. In vitro enzyme assays of wild type and HDS variants exhibit differential activities and reveal an unanticipated mismatch between enzyme kinetics and the in vivo MEcPP levels in the corresponding Rceh lines. Additional analyses attribute the mismatch, in part, to the abundance of the first and rate-limiting MEP-pathway enzyme, DXS, and further suggest MEcPP as a rheostat for abundance of the upstream enzyme instrumental in fine-tuning of the pathway flux. Collectively, this study identifies critical residues of a key MEP-pathway enzyme, HDS, valuable for synthetic engineering of isoprenoids, and as potential targets for rational design of antiinfective drugs.


Assuntos
Substituição de Aminoácidos , Proteínas de Arabidopsis/genética , Arabidopsis/metabolismo , Enzimas/genética , Oxirredutases/genética , Terpenos/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Vias Biossintéticas , Núcleo Celular/metabolismo , Enzimas/metabolismo , Eritritol/análogos & derivados , Eritritol/metabolismo , Ligantes , Simulação de Acoplamento Molecular , Oxirredutases/metabolismo , Plantas Geneticamente Modificadas , Plastídeos/genética , Plastídeos/metabolismo
8.
Plant J ; 105(6): 1582-1599, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33340183

RESUMO

Signals originating within plastids modulate organelle differentiation by transcriptionally regulating nuclear-encoded genes. These retrograde signals are also integral regulators of plant development, including leaf morphology. The clb5 mutant displays severe leaf morphology defects due to Apocarotenoid Signal 1 (ACS1) accumulation in the developmentally arrested plastid. Transcriptomic analysis of clb5 validates that ACS1 accumulation deregulates hundreds of nuclear genes, including the suppression of most genes encoding plastid ribosomal proteins. Herein, we order the molecular events causing the leaf phenotype associated with the accumulation of ACS1, which includes two consecutive retrograde signaling cascades. Firstly, ACS1 originating in the plastid drives inhibition of plastid translation (IPT) via nuclear transcriptome remodeling of chlororibosomal proteins, requiring light as an essential component. Subsequently, IPT results in leaf morphological defects via a GUN1-dependent pathway shared with seedlings undergoing chemical IPT treatments and is restricted to an early window of the leaf development. Collectively, this work advances our understanding of the complexity within plastid retrograde signaling exemplified by sequential signal exchange and consequences that in a particular temporal and spatial context contribute to the modulation of leaf development.


Assuntos
Carotenoides/metabolismo , Folhas de Planta/crescimento & desenvolvimento , Plastídeos/metabolismo , Transdução de Sinais , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Perfilação da Expressão Gênica , Folhas de Planta/metabolismo , Plântula/crescimento & desenvolvimento
9.
J Exp Bot ; 73(21): 7139-7154, 2022 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-35776102

RESUMO

Communication from plastids to the nucleus via retrograde signal cascades is essential to modulate nuclear gene expression, impacting plant development and environmental responses. Recently, a new class of plastid retrograde signals has emerged, consisting of acyclic and cyclic carotenoids and/or their degradation products, apocarotenoids. Although the biochemical identity of many of the apocarotenoid signals is still under current investigation, the examples described herein demonstrate the central roles that these carotenoid-derived signals play in ensuring plant development and survival. We present recent advances in the discovery of apocarotenoid signals and their role in various plant developmental transitions and environmental stress responses. Moreover, we highlight the emerging data exposing the highly complex signal transduction pathways underlying plastid to nucleus apocarotenoid retrograde signaling cascades. Altogether, this review summarizes the central role of the carotenoid pathway as a major source of retrograde signals in plants.


Assuntos
Carotenoides , Plastídeos , Carotenoides/metabolismo , Plastídeos/metabolismo , Desenvolvimento Vegetal , Plantas/metabolismo , Núcleo Celular/metabolismo , Regulação da Expressão Gênica de Plantas
10.
Rev Med Chil ; 150(5): 634-642, 2022 May.
Artigo em Espanhol | MEDLINE | ID: mdl-37906764

RESUMO

BACKGROUND: The confinement caused by the COVID-19 pandemic changed the lifestyles of the population affecting their levels of physical activity. AIM: To determine the factors associated with a low level of physical activity in adults during confinement during the COVID-19 pandemic. MATERIAL AND METHODS: Adults from Chile, Colombia, México and Perú were invited through social networks to answer an online survey. Questions about sociodemographic, health status and lifestyle variables were included. The level of physical activity and sedentary behavior were determined through the short version of the International Physical Activity Questionnaire (IPAQ). RESULTS: The survey was answered by 3,362 adults aged between 18 and 60 years. Respondents more likely to be inactive were women, those with less than eight years of education, those with overweight or obesity, those who smoked at least one cigarette a day, consumed alcohol four or more times a week, slept less than six hours per day and spent more than 6 hours per day in sedentary behaviors. CONCLUSIONS: These findings provide a sociodemographic and lifestyle profile associated with physical inactivity during the period of confinement in Latin American adults. The results confirm the need to promote healthy lifestyles in the population during periods of confinement.


Assuntos
COVID-19 , Adulto , Humanos , Feminino , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Masculino , COVID-19/epidemiologia , Comportamento Sedentário , América Latina/epidemiologia , Pandemias , Exercício Físico
11.
Gac Med Mex ; 158(2): 69-77, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35763826

RESUMO

INTRODUCTION: In pregnant women, a higher risk for developing viral respiratory infections is identified. OBJECTIVE: To analyze sociodemographic characteristics, evolution, clinical manifestations, and complications of pregnant women hospitalized with COVID-19. METHODS: Study conducted at 11 public hospitals; sociodemographic variables, comorbidities, signs and symptoms, laboratory and imaging findings, pregnancy characteristics, treatment and pregnancy outcome were included for analysis. RESULTS: Age ranged between 15 and 40 years; 85.1% were at third trimester of pregnancy, 11.9% at second and 3% at first; 27% had any comorbidity such as obesity, hypertension or asthma; 89.5% had fever, 73.1% cough, 44.8% dyspnea, 43.3% headache and 35.8% myalgia. Diagnoses were mild disease (55.2%), mild pneumonia (26.9%), severe pneumonia (10.4%), severe pneumonia with acute respiratory distress syndrome (4.5%), and severe pneumonia with septic shock (3%); 76.2% had noninvasive oxygen support, and 9%, mechanical ventilation. Pregnancy was interrupted in 53.8%; 95.5% were discharged due to improvement of their condition and 4.5% died. CONCLUSIONS: Age range and symptoms are consistent with those previously reported. Evidence was found of an increase in cesarean section without a clear indication in women with COVID-19.


INTRODUCCIÓN: En las mujeres embarazadas se identifica mayor riesgo de desarrollar infecciones respiratorias virales. OBJETIVO: Analizar características sociodemográficas, evolución, manifestaciones clínicas y complicaciones en mujeres embarazadas con COVID-19 que fueron hospitalizadas. MÉTODOS: Estudio en 11 hospitales públicos; se incluyeron variables sociodemográficas, comorbilidades, síntomas y signos, hallazgos de laboratorio y gabinete, características del embarazo, tratamiento y desenlace de la gestación. RESULTADOS: La edad osciló entre 15 y 40 años; 85.1 % cursaba el tercer trimestre del embarazo, 11.9 % el segundo y 3 % el primero; 27 % presentó alguna comorbilidad como obesidad, hipertensión o asma; 89.5 % presentó fiebre, 73.1 % tos, 44.8 % disnea, 43.3 % cefalea y 35.8 % mialgias. Los diagnósticos fueron enfermedad leve (55.2 %), neumonía leve (26.9 %), neumonía severa (10.4 %), neumonía severa con síndrome de distrés respiratorio agudo (4.5 %) y neumonía severa con choque séptico (3 %); 76.2 % recibió soporte de oxígeno no invasivo y 9 %, ventilación mecánica. Se interrumpió el embarazo en 53.8 %; 95.5 % egresó por mejoría y 4.5 % falleció. CONCLUSIONES: El rango de edad y los síntomas coinciden con los señalados en la literatura especializada. En mujeres con COVID-19 se evidenció el incremento de la operación cesárea sin una indicación clara.


Assuntos
COVID-19 , Pneumonia , Complicações Infecciosas na Gravidez , Adolescente , Adulto , COVID-19/epidemiologia , COVID-19/terapia , Cesárea , Feminino , Humanos , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/terapia , Resultado da Gravidez , Gestantes , Adulto Jovem
12.
Mol Hum Reprod ; 27(4)2021 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-33576824

RESUMO

Transcriptomic approaches are increasingly used in reproductive medicine to identify candidate endometrial biomarkers. However, it is known that endometrial progression in the molecular biology of the menstrual cycle is a main factor that could affect the discovery of disorder-related genes. Therefore, the aim of this study was to systematically review current practices for considering the menstrual cycle effect and to demonstrate its bias in the identification of potential biomarkers. From the 35 studies meeting the criteria, 31.43% did not register the menstrual cycle phase. We analysed the menstrual cycle effect in 11 papers (including 12 studies) from Gene Expression Omnibus: three evaluating endometriosis, two evaluating recurrent implantation failure, one evaluating recurrent pregnancy loss, one evaluating uterine fibroids and five control studies, which collected endometrial samples throughout menstrual cycle. An average of 44.2% more genes were identified after removing menstrual cycle bias using linear models. This effect was observed even if studies were balanced in the proportion of samples collected at different endometrial stages or only in the mid-secretory phase. Our bias correction method increased the statistical power by retrieving more candidate genes than per-phase independent analyses. Thanks to this practice, we discovered 544 novel candidate genes for eutopic endometriosis, 158 genes for ectopic ovarian endometriosis and 27 genes for recurrent implantation failure. In conclusion, we demonstrate that menstrual cycle progression masks molecular biomarkers, provides new guidelines to unmask them and proposes a new classification that distinguishes between biomarkers of disorder or/and menstrual cycle progression.


Assuntos
Endometriose , Doenças Uterinas , Endometriose/genética , Endometriose/metabolismo , Endométrio/metabolismo , Feminino , Humanos , Ciclo Menstrual/genética , Transcriptoma , Doenças Uterinas/metabolismo
13.
Molecules ; 26(16)2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34443302

RESUMO

An approach based on a dendrimer display of B- and T-cell epitopes relevant for antibody induction has been shown to be effective as a foot-and-mouth disease (FMD) vaccine. B2T dendrimers combining two copies of the major FMD virus (FMDV) type O B-cell epitope (capsid proteinVP1 (140-158)) covalently linked to a heterotypic T-cell epitope from non-structural protein 3A (21-35), henceforth B2T-3A, has previously been shown to elicit high neutralizing antibody (nAb) titers and IFN-γ-producing cells in both mice and pigs. Here, we provide evidence that the B- and T-cell epitopes need to be tethered to a single molecular platform for successful T-cell help, leading to efficient nAb induction in mice. In addition, mice immunized with a non-covalent mixture of B2T-3A dendrimers containing the B-cell epitopes of FMDV types O and C induced similarly high nAb levels against both serotypes, opening the way for a multivalent vaccine platform against a variety of serologically different FMDVs. These findings are relevant for the design of vaccine strategies based on B- and T-cell epitope combinations.


Assuntos
Dendrímeros/química , Epitopos de Linfócito T/imunologia , Vírus da Febre Aftosa/imunologia , Peptídeos/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Epitopos de Linfócito B/imunologia , Feminino , Febre Aftosa/imunologia , Febre Aftosa/virologia , Camundongos , Especificidade da Espécie , Suínos
14.
Health Res Policy Syst ; 18(1): 59, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32503569

RESUMO

BACKGROUND: Scientific journals play a critical role in research validation and dissemination and are increasingly vocal about the identification of research priorities and the targeting of research results to key audiences. No new journals specialising in health policy and systems research (HPSR) and focusing in the developing world or in a specific developing world region have been established since the early 1980s. This paper compares the growth of publications on HPSR across Latin America and the world and explores the potential, feasibility and challenges of innovative publication strategies. METHODS: A bibliometric analysis was undertaken using HPSR MeSH terms with journals indexed in Medline. A survey was undertaken among 2500 authors publishing on HPSR in Latin America (LA) through an online survey, with a 13.1% response rate. Aggregate indicators were constructed and validated, and two-way ANOVA tests were performed on key variables. RESULTS: HPSR publications on LA observed an average annual growth of 27.5% from the years 2000 to 2018, as against 11.4% worldwide and yet a lag on papers published per capita. A total of 48 journals with an Impact Factor publish HPSR on LA, of which 5 non-specialised journals are published in the region and are ranked in the bottom quintile of Impact Factor. While the majority of HPSR papers worldwide is published in specialised HPSR journals, in LA this is the minority. Very few researchers from LA sit in the Editorial Board of international journals. Researchers highly support strengthening quality HPSR publications through publishing in open access, on-line journals with a focus on the LA region and with peer reviewers specialized on the region. Researchers would support a new open access journal specializing in the LA region and in HPSR, publishing in English. Open access up-front costs and disincentives while waiting for an Impact Factor can be overcome. CONCLUSION: Researchers publishing on HPSR in LA widely support the launching of a new specialised journal for the region with a vigorous editorial policy focusing on regional and country priorities. Strategies should be in place to support English-language publishing and to develop a community of practice around the publication process. In the first years, special issues should be promoted through a priority-setting process to attract prominent authors, develop the audience and attain an Impact Factor.


Assuntos
Política de Saúde , Pesquisa sobre Serviços de Saúde , Editoração , Bibliometria , Políticas Editoriais , América Latina
15.
Plant J ; 96(4): 828-841, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30144333

RESUMO

The plastidial methylerythritol phosphate (MEP) pathway is an essential route for plants as the source of precursors for all plastidial isoprenoids, many of which are of medical and biotechnological importance. The MEP pathway is highly sensitive to environmental cues as many of these compounds are linked to photosynthesis and growth and light is one of the main regulatory factors. However, the mechanisms coordinating the MEP pathway with light cues are not fully understood. Here we demonstrate that by a differential direct transcriptional modulation, via the key-master integrators of light signal transduction HY5 and PIFs which target the genes that encode the rate-controlling DXS1, DXR and HDR enzymes, light imposes a direct, rapid and potentially multi-faceted response that leads to unique protein dynamics of this pathway, resulting in a significant difference in the protein levels. For DXS1, PIF1/HY5 act as a direct activation/suppression module. In contrast, DXR accumulation in response to light results from HY5 induction with minor contribution of de-repression by PIF1. Finally, HDR transcription increases in the light exclusively by suppression of the PIFs repression. This is an example of how light signaling components can differentially multi-target the initial steps of a pathway whose products branch downstream to all chloroplastic isoprenoids. These findings demonstrate the diversity and flexibility of light signaling components that optimize key biochemical pathways essential for plant growth.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Luz , Proteínas Nucleares/metabolismo , Fatores de Transcrição , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição de Zíper de Leucina Básica/genética , Cloroplastos/metabolismo , Cromatina , Regulação da Expressão Gênica de Plantas , Redes e Vias Metabólicas/genética , Proteínas Nucleares/genética , Fotossíntese , Regiões Promotoras Genéticas , Plântula/genética , Plântula/metabolismo , Transdução de Sinais , Terpenos/metabolismo
16.
Planta ; 250(4): 1177-1189, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31190117

RESUMO

MAIN CONCLUSION: A MAPK module, of which MPK6 kinase is an important component, is involved in the coordination of the responses to Pi and Fe in the primary root meristem of Arabidopsis thaliana. Phosphate (Pi) deficiency induces determinate primary root growth in Arabidopsis through cessation of cell division in the meristem, which is linked to an increased iron (Fe) accumulation. Here, we show that Mitogen-Activated Protein Kinase6 (MPK6) has a role in Arabidopsis primary root growth under low Pi stress. MPK6 activity is induced in roots in response to low Pi, and such induction is enhanced by Fe supplementation, suggesting an MPK6 role in coordinating Pi/Fe balance in mediating root growth. The differentiation of the root meristem induced by low Pi levels correlates with altered expression of auxin-inducible genes and auxin transporter levels via MPK6. Our results indicate a critical role of the MPK6 kinase in coordinating meristem cell activity to Pi and Fe availability for proper primary root growth.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimologia , Ferro/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosfatos/metabolismo , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Transporte Biológico , Divisão Celular , Genes Reporter , Ácidos Indolacéticos/metabolismo , Meristema/enzimologia , Meristema/genética , Meristema/crescimento & desenvolvimento , Proteínas Quinases Ativadas por Mitógeno/genética , Reguladores de Crescimento de Plantas , Raízes de Plantas/enzimologia , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Estresse Fisiológico
17.
J Oral Rehabil ; 46(8): 747-755, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31050014

RESUMO

The aim of this work is to compare the mechanical fatigue behaviour of different crown heights of single crown implant restorations made over two different internal hexagonal titanium dental implant connection levels. Two different groups of internal hexagonal connection were studied: (a) TL group (N = 26) included implants with a transmucosal connection (12.2 mm height and 4.8 mm width) and (b) BL group (N = 26) composed by implants at a bone level connection (10 mm height and 3.8 mm width). Two subgroups (N = 13) were established for each connection level according to crown heights (TL10 = 10 mm, TL15 = 15 mm, BL12 = 12 mm, BL17 = 17 mm). Dynamic load tests were carried out according to ISO Norm 14801. Failed samples and fracture surfaces were analysed with an optical and scanning electron microscope (SEM). The fatigue limit and the fatigue strength degradation (fatigue strength exponent) decreases with increasing crown height (5 mm) in both groups of internal hexagonal titanium dental implant connection levels. Consequently, the mechanical integrity of internal hexagonal dental implants varies with the height of the crown. An increase of 5 millimetres in the crown height appears to significantly decrease the fatigue life of both types of dental implants.


Assuntos
Implantes Dentários , Falha de Restauração Dentária , Parafusos Ósseos , Coroas , Dente Suporte , Projeto do Implante Dentário-Pivô , Prótese Dentária Fixada por Implante , Análise do Estresse Dentário , Fadiga , Humanos , Teste de Materiais , Estresse Mecânico
18.
Plant Mol Biol ; 96(4-5): 339-351, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29344832

RESUMO

KEY MESSAGE: The function and components of L-glutamate signaling pathways in plants have just begun to be elucidated. Here, using a combination of genetic and biochemical strategies, we demonstrated that a MAPK module is involved in the control of root developmental responses to this amino acid. Root system architecture plays an essential role in plant adaptation to biotic and abiotic factors via adjusting signal transduction and gene expression. L-Glutamate (L-Glu), an amino acid with neurotransmitter functions in animals, inhibits root growth, but the underlying genetic mechanisms are poorly understood. Through a combination of genetic analysis, in-gel kinase assays, detailed cell elongation and division measurements and confocal analysis of expression of auxin, quiescent center and stem cell niche related genes, the critical roles of L-Glu in primary root growth acting through the mitogen-activated protein kinase 6 (MPK6) and the dual specificity serine-threonine-tyrosine phosphatase MKP1 could be revealed. In-gel phosphorylation assays revealed a rapid and dose-dependent induction of MPK6 and MPK3 activities in wild-type Arabidopsis seedlings in response to L-Glu. Mutations in MPK6 or MKP1 reduced or increased root cell division and elongation in response to L-Glu, possibly modulating auxin transport and/or response, but in a PLETHORA1 and 2 independent manner. Our data highlight MPK6 and MKP1 as components of an L-Glu pathway linking the auxin response, and cell division for primary root growth.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimologia , Arabidopsis/fisiologia , Ácido Glutâmico/farmacologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Raízes de Plantas/enzimologia , Proteínas Tirosina Fosfatases/metabolismo , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/biossíntese , Proliferação de Células/efeitos dos fármacos , Indução Enzimática/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Ácidos Indolacéticos/farmacologia , Proteínas de Membrana Transportadoras/metabolismo , Meristema/efeitos dos fármacos , Meristema/enzimologia , Proteínas Quinases Ativadas por Mitógeno/biossíntese , Mutação/genética , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Proteínas Tirosina Fosfatases/biossíntese , Fatores de Transcrição/metabolismo
19.
J Am Chem Soc ; 140(11): 3940-3951, 2018 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-29485277

RESUMO

Well-defined organoplatinum(IV) sites were grafted on a Zn(II)-modified SiO2 support via surface organometallic chemistry in toluene at room temperature. Solid-state spectroscopies including XAS, DRIFTS, DRUV-vis, and solid-state (SS) NMR enhanced by dynamic nuclear polarization (DNP), as well as TPR-H2 and TEM techniques revealed highly dispersed (methylcyclopentadienyl)methylplatinum(IV) sites on the surface ((MeCp)PtMe/Zn/SiO2, 1). In addition, computational modeling suggests that the surface reaction of (MeCp)PtMe3 with Zn(II)-modified SiO2 support is thermodynamically favorable (Δ G = -12.4 kcal/mol), likely due to the increased acidity of the hydroxyl group, as indicated by NH3-TPD and DNP-enhanced 17O{1H} SSNMR. In situ DRIFTS and XAS hydrogenation experiments reveal the probable formation of a surface Pt(IV)-H upon hydrogenolysis of Pt-Me groups. The heterogenized organoplatinum(IV)-hydride sites catalyze the selective partial hydrogenation of 1,3-butadiene to butenes (up to 95%) and the reduction of nitrobenzene derivatives to anilines (up to 99%) with excellent tolerance of reduction-sensitive functional groups (olefin, carbonyl, nitrile, halogens) under mild reaction conditions.

20.
Langmuir ; 34(35): 10333-10339, 2018 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-30086633

RESUMO

We studied the diffusion of three model proteins, lysozyme (Lz), bovine hemoglobin (BHb), and bovine serum albumin (BSA), normal to the (111) plane of sintered silica colloidal crystals with three different pore "radii" (7.5, 19, and 27 nm). We demonstrated that these colloidal crystals exhibit size selectivity when the nanopores are sufficiently small (7.5 and 19 nm). Because these nanopores are still larger than the diffusing proteins, the observed size selectivity can be attributed to the tortuosity of the colloidal nanopores. Larger (27 nm) nanopores led to higher transport rates but at the cost of selectivity. In addition to the size selectivity, we also demonstrated that 19 nm nanopores possess shape selectivity for the proteins of comparable molecular weights. We showed that the high temperature sintering required for the preparation of sintered colloidal crystals reduces the extent of interactions between the proteins and the nanopore surface, which appear to play a minor role in the diffusion, and that transport selectivity is decided solely by protein size and shape. Taken together, our observations suggest that sintered silica colloidal crystals constitute promising nanoporous membranes for protein separations, with easily controllable pore size, size and shape selectivity, and minimal surface fouling.


Assuntos
Coloides/química , Difusão , Hemoglobinas/química , Muramidase/química , Soroalbumina Bovina/química , Dióxido de Silício/química , Adsorção , Animais , Bovinos , Galinhas , Nanoporos , Tamanho da Partícula
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