RESUMEN
Motile cilia on the cell surface produce fluid flows in the body and abnormalities in motile cilia cause primary ciliary dyskinesia. Dynein axonemal assembly factor 6 (DNAAF6), a causative gene of primary ciliary dyskinesia, was isolated as an interacting protein with La ribonucleoprotein 6 (LARP6) that regulates ciliogenesis in multiciliated cells (MCCs). In MCCs of Xenopus embryos, LARP6 and DNAAF6 were colocalized in biomolecular condensates termed dynein axonemal particles and synergized to control ciliogenesis. Moreover, tubulin alpha 1c-like mRNA encoding α-tubulin protein, that is a major component of ciliary axoneme, was identified as a target mRNA regulated by binding LARP6. While DNAAF6 was necessary for high α-tubulin protein expression near the apical side of Xenopus MCCs during ciliogenesis, its mutant, which abolishes binding with LARP6, was unable to restore the expression of α-tubulin protein near the apical side of MCCs in Xenopus DNAAF6 morphant. These results indicated that the binding of LARP6 and DNAAF6 in dynein axonemal particles regulates highly expressed α-tubulin protein near the apical side of Xenopus MCCs during ciliogenesis.
Asunto(s)
Cilios , Ribonucleoproteínas , Tubulina (Proteína) , Proteínas de Xenopus , Xenopus laevis , Cilios/metabolismo , Animales , Ribonucleoproteínas/metabolismo , Ribonucleoproteínas/genética , Tubulina (Proteína)/metabolismo , Proteínas de Xenopus/metabolismo , Proteínas de Xenopus/genética , Humanos , Antígeno SS-B , Autoantígenos/metabolismo , Autoantígenos/genética , Unión Proteica , Axonema/metabolismo , ARN Mensajero/metabolismo , ARN Mensajero/genéticaRESUMEN
Hox genes encode transcription factors that play an important role in establishing the basic body plan of animals. In Drosophila, Antennapedia is one of the five genes that make up the Antennapedia complex (ANT-C). Antennapedia determines the identity of the second thoracic segment, known as the mesothorax. Misexpression of Antennapedia at different developmental stages changes the identity of the mesothorax, including the muscles, nervous system, and cuticle. In Drosophila, Antennapedia has two distinct promoters highly regulated throughout development by several transcription factors. Antennapedia proteins are found with other transcription factors in different ANTENNAPEDIA transcriptional complexes to regulate multiple subsets of target genes. In this review, we describe the different mechanisms that regulate the expression and function of Antennapedia and the role of this Hox gene in the development of Drosophila.
Asunto(s)
Proteínas de Drosophila , Factores de Transcripción , Animales , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas de Homeodominio/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Regulación del Desarrollo de la Expresión Génica , Drosophila/genética , Drosophila/metabolismo , Drosophila melanogaster/genéticaRESUMEN
BACKGROUND: Hox proteins interact with DNA and many other proteins, co-factors, transcriptional factors, chromatin remodeling components, non-coding RNAs and even the extracellular matrix that assembles the Hox complexes. The number of interacting partners continues to grow with diverse components and more transcriptional factors than initially thought. Hox complexes present many activities, but their molecular mechanisms to modulate their target genes remain unsolved. RESULTS: In this paper we showed the protein-protein interaction of Antp with Ubx through the homeodomain using BiFC in Drosophila. Analysis of Antp-deletional mutants showed that AntpHD helixes 1 and 2 are required for the interaction with Ubx. Also, we found a novel interaction of Ubx with TBP, in which the PolyQ domain of TBP is required for the interaction. Moreover, we also detected the formation of two new trimeric complexes of Antp with Ubx, TBP and Exd using BiFC-FRET; these proteins, however, do not form a trimeric interaction with BIP2 or TFIIEß. The novel trimeric complexes reduced Antp transcriptional activity, indicating that they could confer specificity for repression. CONCLUSIONS: Our results increase the number of transcriptional factors in the Antp and Ubx interactomes that form two novel trimeric complexes with TBP and Exd. We also report a new Ubx interaction with TBP. These novel interactions provide important clues of the dynamics of Hox-interacting complexes involved in transcriptional regulation, contributing to better understand Hox function.
Asunto(s)
Proteínas de Drosophila , Proteínas de Homeodominio , Proteína de Unión a TATA-Box , Factores de Transcripción , Animales , Proteína con Homeodominio Antennapedia/genética , Proteína con Homeodominio Antennapedia/metabolismo , Drosophila melanogaster/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Regulación de la Expresión Génica , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Unión Proteica , Proteína de Unión a TATA-Box/metabolismo , Proteína de Unión a TATA-Box/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Transcripción GenéticaRESUMEN
Adversity within low- and middle-income countries (LMICs) poses severe threats to neurocognitive development, which can be partially mitigated by high-quality early family experiences. Specifically, maternal scaffolding and home stimulation can buffer cognitive development in LMIC, possibly by protecting underlying neural functioning. However, the association between family experiences and neural activity remains largely unexplored in LMIC contexts. This study explored the relation of early family experiences to later cognitive skills and absolute gamma power (21-45 Hz), a neural marker linked to higher-order cognitive skills. Drawing data from the PEDS trial, a longitudinal study in rural Pakistan, we examined maternal scaffolding at 24 months and home stimulation quality at 18 months as predictors of verbal IQ, executive functions, and absolute gamma at 48 months for 105 mother-child dyads (52 girls). Maternal scaffolding interacted with gender to predict absolute gamma power, such that higher maternal scaffolding was related to higher gamma more strongly for girls. Maternal scaffolding also interacted with absolute gamma to predict executive functions, such that higher gamma was related to better executive functions only when maternal scaffolding was average to high. Individual differences in early family experiences may partially buffer the neural underpinnings of cognitive skills from adversity in LMIC.
Asunto(s)
Desarrollo Infantil , Función Ejecutiva , Relaciones Madre-Hijo , Población Rural , Humanos , Femenino , Masculino , Pakistán , Estudios Longitudinales , Desarrollo Infantil/fisiología , Preescolar , Función Ejecutiva/fisiología , Factores Sexuales , Adulto , ElectroencefalografíaRESUMEN
BACKGROUND: Protein interactions participate in many molecular mechanisms involved in cellular processes. The human TATA box binding protein (hTBP) interacts with Antennapedia (Antp) through its N-terminal region, specifically via its glutamine homopeptides. This PolyQ region acts as a binding site for other transcription factors under normal conditions, but when it expands, it generates spinocerebellar ataxia 17 (SCA17), whose protein aggregates in the brain prevent its correct functioning. OBJECTIVE: To determine whether the hTBP glutamine-rich region is involved in its interaction with homeoproteins and the role it plays in the formation of protein aggregates in SCA17. MATERIAL AND METHODS: We characterized hTBP interaction with other homeoproteins using BiFC, and modeled SCA17 in Drosophila melanogaster by targeting hTBPQ80 to the fly brain using UAS/GAL4. RESULTS: There was hTBP interaction with homeoproteins through its glutamine-rich region, and hTBP protein aggregates with expanded glutamines were found to affect the locomotor capacity of flies. CONCLUSIONS: The study of hTBP interactions opens the possibility for the search for new therapeutic strategies in neurodegenerative pathologies such as SCA17.
ANTECEDENTES: Las interacciones proteicas participan en una gran cantidad de mecanismos moleculares que rigen los procesos celulares. La proteína de unión a la caja TATA humana (hTBP) interacciona con Antennapedia (Antp) a través de su extremo N-terminal, específicamente a través de sus homopéptidos de glutaminas. Esta región PolyQ sirve como sitio de unión a factores de transcripción en condiciones normales, pero cuando se expande genera la ataxia espinal cerebelosa 17 (SCA17), cuyos agregados proteicos en el cerebro impiden su funcionamiento correcto. OBJETIVO: Determinar si la región rica en glutaminas de hTBP interviene en su interacción con homeoproteínas y el papel que tiene en la formación de agregados proteicos en SCA17. MATERIAL Y MÉTODOS: Se caracterizó la interacción de hTBP con otras homeoproteínas usando BiFC y se modeló SCA17 en Drosophila melanogaster dirigiendo hTBPQ80 al cerebro de las moscas usando UAS/GAL4. RESULTADOS: Existió interacción de hTBP con homeoproteínas a través de su región rica en glutaminas. Los agregados proteicos de hTBP con las glutaminas expandidas afectaron la capacidad locomotriz de las moscas. CONCLUSIONES: El estudio de las interacciones de hTBP abre la posibilidad para la búsqueda de nuevas estrategias terapéuticas en patologías neurodegenerativas como SCA17.
Asunto(s)
Drosophila melanogaster , Ataxias Espinocerebelosas , Proteína de Unión a TATA-Box , Animales , Humanos , Encéfalo/metabolismo , Modelos Animales de Enfermedad , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Glutamina/metabolismo , Péptidos/metabolismo , Agregado de Proteínas/fisiología , Ataxias Espinocerebelosas/metabolismo , Ataxias Espinocerebelosas/genética , Proteína de Unión a TATA-Box/metabolismo , Proteína de Unión a TATA-Box/genéticaRESUMEN
Resting-state fMRI studies have revealed that individuals exhibit stable, functionally meaningful divergences in large-scale network organization. The locations with strongest deviations (called network "variants") have a characteristic spatial distribution, with qualitative evidence from prior reports suggesting that this distribution differs across hemispheres. Hemispheric asymmetries can inform us on constraints guiding the development of these idiosyncratic regions. Here, we used data from the Human Connectome Project to systematically investigate hemispheric differences in network variants. Variants were significantly larger in the right hemisphere, particularly along the frontal operculum and medial frontal cortex. Variants in the left hemisphere appeared most commonly around the TPJ. We investigated how variant asymmetries vary by functional network and how they compare with typical network distributions. For some networks, variants seemingly increase group-average network asymmetries (e.g., the group-average language network is slightly bigger in the left hemisphere and variants also appeared more frequently in that hemisphere). For other networks, variants counter the group-average network asymmetries (e.g., the default mode network is slightly bigger in the left hemisphere, but variants were more frequent in the right hemisphere). Intriguingly, left- and right-handers differed in their network variant asymmetries for the cingulo-opercular and frontoparietal networks, suggesting that variant asymmetries are connected to lateralized traits. These findings demonstrate that idiosyncratic aspects of brain organization differ systematically across the hemispheres. We discuss how these asymmetries in brain organization may inform us on developmental constraints of network variants and how they may relate to functions differentially linked to the two hemispheres.
Asunto(s)
Mapeo Encefálico , Conectoma , Humanos , Individualidad , Lateralidad Funcional , Encéfalo/diagnóstico por imagen , Lóbulo Frontal , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND: Vitamin B12 is essential for deoxyribonucleic acid synthesis and genome stability. A deficiency of vitamin B12 is associated with telomere shortening, genomic aging, and increased risk of chronic disease and mortality. OBJECTIVES: The study aims to determine the effect of vitamin B12 supplementation on leukocyte telomere length (LTL) in infants at risk of vitamin B12 deficiency. METHODS: The study was a predefined secondary analysis of a randomized controlled trial enrolling 600 Nepalese infants aged 6 -11 mo, who were supplemented with 2 µg (2-3 recommended daily allowances) vitamin B12 or placebo daily for 1 y. At the end of the study, LTL was measured in 497 participants. Mean LTL was compared between the treatment arms in the full sample and predefined subgroups based on markers of vitamin B12 status, hemoglobin, sex, and growth indices. RESULTS: LTL at end-study did not differ between the vitamin B12 and placebo arm with a standardized mean difference (95% confidence interval) of 0.04 (-0.14, 0.21). There was no effect of vitamin B12 on LTL in any of the subgroups. CONCLUSIONS: Providing daily vitamin B12 for 1 y during infancy in a population at risk of vitamin B12 deficiency does not affect LTL. This trial was registered at clinicaltrials.gov as NCT02272842.
RESUMEN
BACKGROUND: Myo1e is a nonmuscle motor protein enriched in podocytes. Mutations in MYO1E are associated with steroid-resistant nephrotic syndrome (SRNS). Most of the MYO1E variants identified by genomic sequencing have not been functionally characterized. Here, we set out to analyze two mutations in the Myo1e motor domain, T119I and D388H, which were selected on the basis of protein sequence conservation. METHODS: EGFP-tagged human Myo1e constructs were delivered into the Myo1e-KO mouse podocyte-derived cells via adenoviral infection to analyze Myo1e protein stability, Myo1e localization, and clathrin-dependent endocytosis, which is known to involve Myo1e activity. Furthermore, truncated Myo1e constructs were expressed using the baculovirus expression system and used to measure Myo1e ATPase and motor activity in vitro. RESULTS: Both mutants were expressed as full-length proteins in the Myo1e-KO cells. However, unlike wild-type (WT) Myo1e, the T119I variant was not enriched at the cell junctions or clathrin-coated vesicles (CCVs). In contrast, D388H variant localization was similar to that of WT. The rate of dissociation of the D388H variant from cell-cell junctions and CCVs was decreased, suggesting this mutation affects Myo1e interactions with binding partners. ATPase activity and ability to translocate actin filaments were drastically reduced for the D388H mutant, supporting findings from cell-based experiments. CONCLUSIONS: T119I and D388H mutations are deleterious to Myo1e functions. The experimental approaches used in this study can be applied to future characterization of novel MYO1E variants associated with SRNS.
Asunto(s)
Miosina Tipo I , Síndrome Nefrótico , Animales , Humanos , Ratones , Mutación , Miosina Tipo I/genética , Miosina Tipo I/metabolismo , Síndrome Nefrótico/genética , EsteroidesRESUMEN
INTRODUCTION: Colombia has 50,912,429 inhabitants, but only 50-70% of the population can effectively access health care services. The emergency room (ER) is a main contributor to the in-hospital care system since up to half of the admissions come through it. Telemedicine has become a tool to facilitate effective access to health care services, improve the timeliness of care, reduce diagnostic variability, and reduce costs associated with health. The aim of this study is to describe the experience of a Distance Emergency Care Program through Telemedicine (TelEmergency) to improve specialist access for patients at the Emergency Room (ER) in low- and medium-level care hospitals in Colombia. METHODS: An observational descriptive study of a cohort including 1,544 patients during the program's first two years was conducted. Descriptive statistics were used to analyze the available data. The data are presented with summarized statistics of sociodemographic, clinical, and patient-care variables. RESULTS: The study included a total of 1,544 patients, and the majority were adults between 60 and 79 years of age (n = 491, 32%). More than half were men (n = 832, 54%), and 68% (n = 1,057) belonged to the contributory health care regime. The service was requested from 346 municipalities, 70% (n = 1,076) from intermediate and rural settings. The most common diagnoses were related to COVID-19 (n = 356, 22%), respiratory diseases (n = 217, 14%), and cardiovascular diseases (n = 162, 10%). We observed 44% (n = 681) of local admissions either under observation (n = 53, 3%) or hospitalization (n = 380, 24%), limiting the need for hospital transfers. Program operation data revealed that 50% (n = 799) of requests were answered within two hours by the medical staff. The initial diagnosis was modified in 7% (n = 119) of the patients after being evaluated by specialists at the TelEmergency program. CONCLUSIONS: This study shows the operational data collected during the first two years after the implementation of the TelEmergency program in Colombia, the first of its kind in the country. Its implementation offered specialized timely management of patients at the ER in low- and medium-level care hospitals, where there is no availability of specialized doctors.
Asunto(s)
COVID-19 , Telemedicina , Masculino , Adulto , Humanos , Femenino , Colombia/epidemiología , COVID-19/epidemiología , Hospitalización , América del SurRESUMEN
Structure-activity relationship (SAR) studies allow the evaluation of the relationship between structural chemical changes and biological activity. Fluoroquinolones have chemical characteristics that allow their structure to be modified and new analogs with different therapeutic properties to be generated. The objective of this research is to identify and select the C-7 heterocycle fluoroquinolone analog (FQH 1-5) with antibacterial activity similar to the reference fluoroquinolone through in vitro, in silico, and in vivo evaluations. First, SAR analysis was conducted on the FQH 1-5, using an in vitro antimicrobial sensibility model in order to select the best compound. Then, an in silico model mechanism of action analysis was carried out by molecular docking. The non-bacterial cell cytotoxicity was evaluated, and finally, the antimicrobial potential was determined by an in vivo model of topical infection in mice. The results showed antimicrobial differences between the FQH 1-5 and Gram-positive and Gram-negative bacteria, identifying the 7-benzimidazol-1-yl-fluoroquinolone (FQH-2) as the most active against S. aureus. Suggesting the same mechanism of action as the other fluoroquinolones; no cytotoxic effects on non-bacterial cells were found. FQH-2 was demonstrated to decrease the amount of bacteria in infected wound tissue.
Asunto(s)
Antibacterianos , Antiinfecciosos , Animales , Ratones , Antibacterianos/farmacología , Fluoroquinolonas/farmacología , Simulación del Acoplamiento Molecular , Staphylococcus aureus , Bacterias Gramnegativas , Bacterias Grampositivas , Relación Estructura-ActividadRESUMEN
Ageing displays a low-grade pro-inflammatory profile in blood and the brain. Accumulation of pro-inflammatory cytokines, microglia activation and volumetric changes in the brain correlate with cognitive decline in ageing models. However, the interplay between them is not totally understood. Here, we aimed to globally identify an age-dependent pro-inflammatory profile and microglia morphological plasticity that favors major volume changes in the brain associated with cognitive decline. Cluster analysis of behavioral data obtained from 2-,12- and 20-month-old male C57BL/6 mice revealed age-dependent cognitive decline after the Y-maze, Barnes maze, object recognition (NORT) and object location tests (OLT). Global magnetic resonance imageing (MRI) analysis by deformation-based morphometry (DBM) in the brain identified a volume increase in the fornix and a decrease in the left medial entorhinal cortex (MEntC) during ageing. Notably, the fornix shows an increase in the accumulation of pro-inflammatory cytokines, whereas the left MEntC displays a decrease. Morphological assessment of microglia also confirms an active and dystrophic phenotype in the fornix and a surveillance phenotype in the left MEntC. Finally, biological modeling revealed that age-related volume increase in the fornix was associated with dystrophic microglia and cognitive impairment, as evidenced by failure on tasks examining memory of object location and novelty. Our results propose that the morphological plasticity of microglia might contribute to volumetric changes in brain regions associated with cognitive decline during physiological ageing.
Asunto(s)
Disfunción Cognitiva , Microglía , Envejecimiento , Animales , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/patología , Citocinas , Humanos , Masculino , Trastornos de la Memoria/diagnóstico por imagen , Trastornos de la Memoria/patología , Ratones , Ratones Endogámicos C57BL , Memoria Espacial/fisiologíaRESUMEN
Post-transcriptional regulation via small regulatory RNAs (sRNAs) has been implicated in diverse regulatory processes in bacteria, including virulence. One class of sRNAs, termed trans-acting sRNAs, can affect the stability and/or the translational efficiency of regulated transcripts. In this study, we utilized a collaborative approach that employed data from infection with the Borrelia burgdorferi Tn library, coupled with Tn-seq, together with borrelial sRNA and total RNA transcriptomes, to identify an intergenic trans-acting sRNA, which we designate here as ittA for infectivity-associated and tissue-tropic sRNA locus A. The genetic inactivation of ittA resulted in a significant attenuation in infectivity, with decreased spirochetal load in ear, heart, skin and joint tissues. In addition, the ittA mutant did not disseminate to peripheral skin sites or heart tissue, suggesting a role for ittA in regulating a tissue-tropic response. RNA-Seq analysis determined that 19 transcripts were differentially expressed in the ittA mutant relative to its genetic parent, including vraA, bba66, ospD and oms28 (bba74). Subsequent proteomic analyses also showed a significant decrease of OspD and Oms28 (BBA74) proteins. To our knowledge this is the first documented intergenic sRNA that alters the infectivity potential of B. burgdorferi.
Asunto(s)
Borrelia burgdorferi/genética , ARN Pequeño no Traducido/metabolismo , Tropismo/genética , Borrelia burgdorferi/metabolismo , Borrelia burgdorferi/patogenicidad , Regulación Bacteriana de la Expresión Génica/genética , Biblioteca de Genes , Genoma Bacteriano , Enfermedad de Lyme/microbiología , Proteómica , ARN Bacteriano/genética , ARN Pequeño no Traducido/genética , Transcriptoma/genética , VirulenciaRESUMEN
BACKGROUND: Coronavirus disease 2019 (COVID-19) causes a mild illness in most cases; forecasting COVID-19-associated mortality and the demand for hospital beds and ventilators are crucial for rationing countries' resources. OBJECTIVE: To evaluate factors associated with the severity of COVID-19 in Mexico and to develop and validate a score to predict severity in patients with COVID-19 infection in Mexico. DESIGN: Retrospective cohort. PARTICIPANTS: We included 1,435,316 patients with COVID-19 included before the first vaccine application in Mexico; 725,289 (50.5%) were men; patient's mean age (standard deviation (SD)) was 43.9 (16.9) years; 21.7% of patients were considered severe COVID-19 because they were hospitalized, died or both. MAIN MEASURES: We assessed demographic variables, smoking status, pregnancy, and comorbidities. Backward selection of variables was used to derive and validate a model to predict the severity of COVID-19. KEY RESULTS: We developed a logistic regression model with 14 main variables, splines, and interactions that may predict the probability of COVID-19 severity (area under the curve for the validation cohort = 82.4%). CONCLUSIONS: We developed a new model able to predict the severity of COVID-19 in Mexican patients. This model could be helpful in epidemiology and medical decisions.
Asunto(s)
COVID-19 , Hospitalización , Humanos , Masculino , México/epidemiología , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2RESUMEN
BACKGROUND: Hox proteins finely coordinate antero-posterior axis during embryonic development and through their action specific target genes are expressed at the right time and space to determine the embryo body plan. As master transcriptional regulators, Hox proteins recognize DNA through the homeodomain (HD) and interact with a multitude of proteins, including general transcription factors and other cofactors. HD binding specificity increases by protein-protein interactions with a diversity of cofactors that outline the Hox interactome and determine the transcriptional landscape of the selected target genes. All these interactions clearly demonstrate Hox-driven transcriptional regulation, but its precise mechanism remains to be elucidated. RESULTS: Here we report Antennapedia (Antp) Hox protein-protein interaction with the TATA-binding protein (TBP) and the formation of novel trimeric complexes with TFIIEß and Extradenticle (Exd), as well as its participation in transcriptional regulation. Using Bimolecular Fluorescence Complementation (BiFC), we detected the interaction of Antp-TBP and, in combination with Förster Resonance Energy Transfer (BiFC-FRET), the formation of the trimeric complex with TFIIEß and Exd in living cells. Mutational analysis showed that Antp interacts with TBP through their N-terminal polyglutamine-stretches. The trimeric complexes of Antp-TBP with TFIIEß and Exd were validated using different Antp mutations to disrupt the trimeric complexes. Interestingly, the trimeric complex Antp-TBP-TFIIEß significantly increased the transcriptional activity of Antp, whereas Exd diminished its transactivation. CONCLUSIONS: Our findings provide important insights into the Antp interactome with the direct interaction of Antp with TBP and the two new trimeric complexes with TFIIEß and Exd. These novel interactions open the possibility to analyze promoter function and gene expression to measure transcription factor binding dynamics at target sites throughout the genome.
Asunto(s)
Proteína con Homeodominio Antennapedia , Proteínas de Drosophila , Proteínas de Homeodominio , Proteína de Unión a TATA-Box , Factores de Transcripción TFII , Factores de Transcripción , Proteína con Homeodominio Antennapedia/genética , Proteína con Homeodominio Antennapedia/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Regulación del Desarrollo de la Expresión Génica , Células HEK293 , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Humanos , Proteína de Unión a TATA-Box/genética , Proteína de Unión a TATA-Box/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Factores de Transcripción TFII/genética , Factores de Transcripción TFII/metabolismoRESUMEN
Social interactions are essential for infant brain development, yet we know little about how infant functional connectivity differs between social and nonsocial contexts, or how sensitivity to differences between contexts might be related to early distal and proximal environmental factors. We compared 12-month-old infants' intrahemispheric electroencephalographic (EEG) coherence between a social and a nonsocial condition, then examined whether differences between conditions varied as a function of family economic strain and two maternal behaviors at 6 months, positive affect and infant-directed speech. We found lower EEG coherence from the frontal region to the central, parietal, temporal, and occipital regions during the social condition, but only for infants from higher-income families and infants whose mothers used higher proportions of infant-directed speech. In contrast, there were no differences between social and nonsocial conditions for infants from economically strained families or infants whose mothers used lower proportions of infant-directed speech. This study demonstrates that neural organization differs between a nonsocial baseline and a social interaction, but said differentiation is not present for infants from less privileged backgrounds. Our results underscore the importance of examining brain activity during species-typical contexts to understand the role of environmental factors in brain development.
Asunto(s)
Interacción Social , Habla , Desarrollo Infantil , Electroencefalografía , Femenino , Humanos , Lactante , MadresRESUMEN
The aim of this review is to provide an overview of the present association between Intermittent Fasting (IF), the Gut Microbiota (GM), and the adipocyte with respect to Metabolic Health (MH). A search was carried out through Dialnet, Scielo, Web of Science, Redalyc and PubMed, using keywords such as: "intermittent fasting", "time-restricted feeding", "gut microbiota" and "Metabolic Health". Intermittent fasting (IF) regimens promote weight loss, therefore contributing to improved metabolic health. IF beneficially participates in the modulation of the intestinal microbiome, allowing a continuous interaction with nutrients to be digested and shaping the intestinal immune responses during the development of cardiovascular disease, blood pressure and diabetes mellitus through metabolic activities.
Asunto(s)
Microbioma Gastrointestinal , Adipocitos , Ayuno , Microbioma Gastrointestinal/fisiología , Humanos , IntestinosRESUMEN
Recent work has demonstrated that individual-specific variations in functional networks (termed "network variants") can be identified in individuals using resting state functional magnetic resonance imaging (fMRI). These network variants exhibit reliability over time, suggesting that they may be trait-like markers of individual differences in brain organization. However, while networks variants are reliable at rest, is is still untested whether they are stable between task and rest states. Here, we use precision data from the Midnight Scan Club (MSC) to demonstrate that (1) task data can be used to identify network variants reliably, (2) these network variants show substantial spatial overlap with those observed in rest, although state-specific effects are present, (3) network variants assign to similar canonical functional networks in task and rest states, and (4) single tasks or a combination of multiple tasks produce similar network variants to rest. Together, these findings further reinforce the trait-like nature of network variants and demonstrate the utility of using task data to define network variants.
Asunto(s)
Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiología , Desempeño Psicomotor/fisiología , Descanso/fisiología , Análisis de Datos , Bases de Datos Factuales/tendencias , Humanos , Imagen por Resonancia Magnética/tendenciasRESUMEN
Autism spectrum disorder (ASD) is a complex neurodevelopmental disease which involves functional and structural defects in selective central nervous system (CNS) regions that harm function and individual ability to process and respond to external stimuli. Individuals with ASD spend less time engaging in social interaction compared to non-affected subjects. Studies employing structural and functional magnetic resonance imaging reported morphological and functional abnormalities in the connectivity of the mesocorticolimbic reward pathway between the nucleus accumbens and the ventral tegmental area (VTA) in response to social stimuli, as well as diminished medial prefrontal cortex in response to visual cues, whereas stronger reward system responses for the non-social realm (e.g., video games) than social rewards (e.g., approval), associated with caudate nucleus responsiveness in ASD children. Defects in the mesocorticolimbic reward pathway have been modulated in transgenic murine models using D2 dopamine receptor heterozygous (D2+/-) or dopamine transporter knockout mice, which exhibit sociability deficits and repetitive behaviors observed in ASD phenotypes. Notably, the mesocorticolimbic reward pathway is modulated by systemic and central inflammation, such as primed microglia, which occurs during obesity or maternal overnutrition. Therefore, we propose that a positive energy balance during obesity/maternal overnutrition coordinates a systemic and central inflammatory crosstalk that modulates the dopaminergic neurotransmission in selective brain areas of the mesocorticolimbic reward pathway. Here, we will describe how obesity/maternal overnutrition may prime microglia, causing abnormalities in dopamine neurotransmission of the mesocorticolimbic reward pathway, postulating a possible immune role in the development of ASD.
Asunto(s)
Trastorno del Espectro Autista/metabolismo , Sistema Límbico/metabolismo , Microglía/metabolismo , Red Nerviosa/metabolismo , Obesidad/metabolismo , Corteza Prefrontal/metabolismo , Trastorno del Espectro Autista/epidemiología , Trastorno del Espectro Autista/patología , Humanos , Sistema Límbico/patología , Microglía/patología , Red Nerviosa/patología , Obesidad/epidemiología , Obesidad/patología , Corteza Prefrontal/patologíaRESUMEN
To date, mother-to-fetus transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19) pandemic, remains controversial. Although placental COVID-19 infection has been documented in some cases during the second- and third-trimesters, no reports are available for the first trimester of pregnancy, and no SARS-CoV-2 protein has been found in fetal tissues. We studied the placenta and fetal organs from an early pregnancy miscarriage in a COVID-19 maternal infection by immunohistochemical, reverse transcription quantitative real-time polymerase chain reaction, immunofluorescence, and electron microscopy methods. SARS-CoV-2 nucleocapsid protein, viral RNA, and particles consistent with coronavirus were found in the placenta and fetal tissues, accompanied by RNA replication revealed by double-stranded RNA (dsRNA) positive immunostain. Prominent damage of the placenta and fetal organs were associated with a hyperinflammatory process identified by histological examination and immunohistochemistry. The findings provided in this study document that congenital SARS-CoV-2 infection is possible during the first trimester of pregnancy and that fetal organs, such as lung and kidney, are targets for coronavirus. The infection and multi-organic fetal inflammation produced by SARS-CoV-2 during early pregnancy should alert clinicians in the assessment and management of pregnant women for possible fetal consequences and adverse perinatal outcomes.
Asunto(s)
COVID-19/transmisión , Transmisión Vertical de Enfermedad Infecciosa , Placenta/virología , Complicaciones Infecciosas del Embarazo/virología , SARS-CoV-2/metabolismo , Aborto Espontáneo/virología , Adulto , COVID-19/patología , Femenino , Feto/patología , Feto/virología , Humanos , Placenta/patología , Embarazo , Resultado del Embarazo , Primer Trimestre del Embarazo , Mujeres Embarazadas , ARN Viral/análisisRESUMEN
BACKGROUND: Identifying ineffective practices that have been used in oncology is important in reducing wasted resources and harm. We sought to examine the prevalence of practices that are being used but have been shown in RCTs to be ineffective (medical reversals) in published oncology studies. METHODS: We cross-sectionally analyzed studies published in three high-impact oncology medical journals (2009-2018). We abstracted data relating to the frequency and characterization of medical reversals. RESULTS: Of the 64 oncology reversals, medications (44%) represented the most common intervention type (39% were targeted). Fourteen (22%) were funded by pharmaceutical/industry only and 56% were funded by an organization other than pharmaceutical/industry. The median number of years that the practice had been in use prior to the reversal study was 9 years (range 1-50 years). CONCLUSION: Here we show that oncology reversals most often involve the administration of medications, have been practiced for years, and are often identified through studies funded by non-industry organizations.