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1.
Food Chem ; 334: 127614, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-32711282

RESUMEN

Pectin polysaccharide is an important phytochemical with potential biomedical applications. It is commonly measured by time-consuming destructive chemical methods. This work demonstrates the feasibility of using visible and near-infrared hyperspectral imaging (HSI) techniques to rapidly measure pectin polysaccharides in intact mulberry fruits. Based on spatial information provided by HSI images, the representative spectrum of each whole mulberry was accurately extracted without background. The effects of storage temperature on two varieties of mulberries for model establishment were studied. The performances of two spectral ranges obtained by Si and InGaAs CCD detectors for pectin prediction were compared. The best predictions were obtained from dilute alkali soluble pectin and total soluble pectin in Dashi mulberry fruit stored at room temperature, with residual predictive deviation values of 2.317 and 1.935, respectively. Our results show that HSI is a promising alternative to the chemical method to rapidly and nondestructively measure the pectin content.


Asunto(s)
Análisis de los Alimentos/métodos , Frutas/química , Morus/química , Pectinas/análisis , Espectroscopía Infrarroja Corta/métodos , Almacenamiento de Alimentos , Procesamiento de Imagen Asistido por Computador , Modelos Biológicos , Pectinas/química , Temperatura
2.
Phys Rev Lett ; 125(17): 178001, 2020 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-33156660

RESUMEN

While living organisms have mastered the dynamic control of residual stresses within sheets to induce shape transformation and locomotion, man-made implementations are rudimentary. We present the first autonomously shape-shifting sheets made of a gel that shrinks and swells in response to the phase of an oscillatory chemical (Belousov-Zhabotinsky) reaction. Propagating reaction-diffusion fronts induce localized deformation of the gel. We show that these localized deformations prescribe a spatiotemporal pattern of Gaussian curvature, leading to time-periodic global shape changes. We present the computational tools and experimental protocols needed to control this system, principally the relationship between the Gaussian curvature and the reaction phase, and optical imprinting of the wave pattern. Together, our results demonstrate a route for developing fully autonomous soft machines mimicking some of the locomotive capabilities of living organisms.


Asunto(s)
Materiales Biomiméticos/química , Membranas/química , Modelos Biológicos , Modelos Químicos , Elasticidad , Geles/química , Estrés Mecánico
3.
Nat Commun ; 11(1): 5545, 2020 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-33139718

RESUMEN

During development, cells gain positional information through the interpretation of dynamic morphogen gradients. A proposed mechanism for interpreting opposing morphogen gradients is mutual inhibition of downstream transcription factors, but isolating the role of this specific motif within a natural network remains a challenge. Here, we engineer a synthetic morphogen-induced mutual inhibition circuit in E. coli populations and show that mutual inhibition alone is sufficient to produce stable domains of gene expression in response to dynamic morphogen gradients, provided the spatial average of the morphogens falls within the region of bistability at the single cell level. When we add sender devices, the resulting patterning circuit produces theoretically predicted self-organised gene expression domains in response to a single gradient. We develop computational models of our synthetic circuits parameterised to timecourse fluorescence data, providing both a theoretical and experimental framework for engineering morphogen-induced spatial patterning in cell populations.


Asunto(s)
Escherichia coli/citología , Escherichia coli/crecimiento & desarrollo , Escherichia coli/genética , Simulación por Computador , Regulación Bacteriana de la Expresión Génica , Redes Reguladoras de Genes , Modelos Biológicos , Biología Sintética , Factores de Transcripción
4.
Nat Commun ; 11(1): 5515, 2020 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-33168823

RESUMEN

The carbon sink capacity of tropical forests is substantially affected by tree mortality. However, the main drivers of tropical tree death remain largely unknown. Here we present a pan-Amazonian assessment of how and why trees die, analysing over 120,000 trees representing > 3800 species from 189 long-term RAINFOR forest plots. While tree mortality rates vary greatly Amazon-wide, on average trees are as likely to die standing as they are broken or uprooted-modes of death with different ecological consequences. Species-level growth rate is the single most important predictor of tree death in Amazonia, with faster-growing species being at higher risk. Within species, however, the slowest-growing trees are at greatest risk while the effect of tree size varies across the basin. In the driest Amazonian region species-level bioclimatic distributional patterns also predict the risk of death, suggesting that these forests are experiencing climatic conditions beyond their adaptative limits. These results provide not only a holistic pan-Amazonian picture of tree death but large-scale evidence for the overarching importance of the growth-survival trade-off in driving tropical tree mortality.


Asunto(s)
Ecología , Bosques , Árboles/crecimiento & desarrollo , Biomasa , Brasil , Dióxido de Carbono , Secuestro de Carbono , Ecosistema , Monitoreo del Ambiente , Modelos Biológicos , Modelos de Riesgos Proporcionales , Factores de Riesgo , Clima Tropical
5.
J R Soc Interface ; 17(172): 20200393, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33143594

RESUMEN

The basic reproductive number, R0, is one of the most common and most commonly misapplied numbers in public health. Often used to compare outbreaks and forecast pandemic risk, this single number belies the complexity that different epidemics can exhibit, even when they have the same R0. Here, we reformulate and extend a classic result from random network theory to forecast the size of an epidemic using estimates of the distribution of secondary infections, leveraging both its average R0 and the underlying heterogeneity. Importantly, epidemics with lower R0 can be larger if they spread more homogeneously (and are therefore more robust to stochastic fluctuations). We illustrate the potential of this approach using different real epidemics with known estimates for R0, heterogeneity and epidemic size in the absence of significant intervention. Further, we discuss the different ways in which this framework can be implemented in the data-scarce reality of emerging pathogens. Lastly, we demonstrate that without data on the heterogeneity in secondary infections for emerging infectious diseases like COVID-19 the uncertainty in outbreak size ranges dramatically. Taken together, our work highlights the critical need for contact tracing during emerging infectious disease outbreaks and the need to look beyond R0.


Asunto(s)
Betacoronavirus , Coinfección/complicaciones , Enfermedades Transmisibles Emergentes/epidemiología , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/epidemiología , Modelos Biológicos , Neumonía Viral/complicaciones , Neumonía Viral/epidemiología , Trazado de Contacto , Infecciones por Coronavirus/transmisión , Humanos , Pandemias , Neumonía Viral/transmisión , Factores de Riesgo
6.
Comput Biol Med ; 126: 104051, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33131530

RESUMEN

SARS-CoV-2 has ushered a global pandemic with no effective drug being available at present. Although several FDA-approved drugs are currently under clinical trials for drug repositioning, there is an on-going global effort for new drug identification. In this paper, using multi-omics (interactome, proteome, transcriptome, and bibliome) data and subsequent integrated analysis, we present the biological events associated with SARS-CoV-2 infection and identify several candidate drugs against this viral disease. We found that: (i) Interactome-based infection pathways differ from the other three omics-based profiles. (ii) Viral process, mRNA splicing, cytokine and interferon signaling, and ubiquitin mediated proteolysis are important pathways in SARS-CoV-2 infection. (iii) SARS-CoV-2 infection also shares pathways with Influenza A, Epstein-Barr virus, HTLV-I, Measles, and Hepatitis virus. (iv) Further, bacterial, parasitic, and protozoan infection pathways such as Tuberculosis, Malaria, and Leishmaniasis are also shared by this virus. (v) A total of 50 candidate drugs, including the prophylaxis agents and pathway specific inhibitors are identified against COVID-19. (vi) Betamethasone, Estrogen, Simvastatin, Hydrocortisone, Tositumomab, Cyclosporin A etc. are among the important drugs. (vii) Ozone, Nitric oxide, plasma components, and photosensitizer drugs are also identified as possible therapeutic candidates. (viii) Curcumin, Retinoic acids, Vitamin D, Arsenic, Copper, and Zinc may be the candidate prophylaxis agents. Nearly 70% of our identified agents are previously suggested to have anti-COVID-19 effects or under clinical trials. Among our identified drugs, the ones that are not yet tested, need validation with caution while an appropriate drug combination from these candidate drugs along with a SARS-CoV-2 specific antiviral agent is needed for effective COVID-19 management.


Asunto(s)
Antivirales , Betacoronavirus , Infecciones por Coronavirus , Bases de Datos Genéticas , Descubrimiento de Drogas , Modelos Biológicos , Pandemias , Neumonía Viral , Antivirales/química , Antivirales/farmacocinética , Antivirales/uso terapéutico , Betacoronavirus/genética , Betacoronavirus/metabolismo , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/genética , Infecciones por Coronavirus/metabolismo , Humanos , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/genética , Neumonía Viral/metabolismo , Proteómica
7.
Elife ; 92020 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-33140720

RESUMEN

A mathematical model shows how the shape of early multicellular organisms may have helped cells evolve specialized roles.


Asunto(s)
Evolución Biológica , Modelos Biológicos , Reproducción
8.
PLoS One ; 15(11): e0242128, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33175914

RESUMEN

BACKGROUND: The coronavirus (SARS-COV-2) is now a global concern because of its higher transmission capacity and associated adverse consequences including death. The reproductive number of coronavirus provides an estimate of the possible extent of the transmission. This study aims to provide a summary reproductive number of coronavirus based on available global level evidence. METHODS: A total of three databases were searched on September 15, 2020: PubMed, Web of Science, and Science Direct. The searches were conducted using a pre-specified search strategy to record studies reported the reproductive number of coronavirus from its inception in December 2019. It includes keywords of coronavirus and its reproductive number, which were combined using the Boolean operators (AND, OR). Based on the included studies, we estimated a summary reproductive number by using the meta-analysis. We used narrative synthesis to explain the results of the studies where the reproductive number was reported, however, were not possible to include in the meta-analysis because of the lack of data (mostly due to confidence interval was not reported). RESULTS: Total of 42 studies included in this review whereas 29 of them were included in the meta-analysis. The estimated summary reproductive number was 2.87 (95% CI, 2.39-3.44). We found evidence of very high heterogeneity (99.5%) of the reproductive number reported in the included studies. Our sub-group analysis was found the significant variations of reproductive number across the country for which it was estimated, method and model that were used to estimate the reproductive number, number of case that was considered to estimate the reproductive number, and the type of reproductive number that was estimated. The highest reproductive number was reported for the Diamond Princess Cruise Ship in Japan (14.8). In the country-level, the higher reproductive number was reported for France (R, 6.32, 95% CI, 5.72-6.99) following Germany (R, 6.07, 95% CI, 5.51-6.69) and Spain (R, 3.56, 95% CI, 1.62-7.82). The higher reproductive number was reported if it was estimated by using the Markov Chain Monte Carlo method (MCMC) method and the Epidemic curve model. We also reported significant heterogeneity of the type of reproductive number- a high-value reported if it was the time-dependent reproductive number. CONCLUSION: The estimated summary reproductive number indicates an exponential increase of coronavirus infection in the coming days. Comprehensive policies and programs are important to reduce new infections as well as the associated adverse consequences including death.


Asunto(s)
Infecciones por Coronavirus/epidemiología , Brotes de Enfermedades/estadística & datos numéricos , Neumonía Viral/epidemiología , Betacoronavirus/aislamiento & purificación , Simulación por Computador , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Bases de Datos Factuales , Humanos , Modelos Biológicos , Pandemias , Neumonía Viral/transmisión , Neumonía Viral/virología
9.
Stem Cell Res Ther ; 11(1): 448, 2020 10 23.
Artículo en Inglés | MEDLINE | ID: mdl-33097094

RESUMEN

Gene therapy is being investigated for a range of serious lung diseases, such as cystic fibrosis and emphysema. Recombinant adeno-associated virus (rAAV) is a well-established, safe, viral vector for gene delivery with multiple naturally occurring and artificial serotypes available displaying alternate cell, tissue, and species-specific tropisms. Efficient AAV serotypes for the transduction of the conducting airways have been identified for several species; however, efficient serotypes for human lung parenchyma have not yet been identified. Here, we screened the ability of multiple AAV serotypes to transduce lung bud organoids (LBOs)-a model of human lung parenchyma generated from human embryonic stem cells. Microinjection of LBOs allowed us to model transduction from the luminal surface, similar to dosing via vector inhalation. We identified the naturally occurring rAAV2 and rAAV6 serotypes, along with synthetic rAAV6 variants, as having tropism for the human lung parenchyma. Positive staining of LBOs for surfactant proteins B and C confirmed distal lung identity and suggested the suitability of these vectors for the transduction of alveolar type II cells. Our findings establish LBOs as a new model for pulmonary gene therapy and stress the relevance of LBOs as a viral infection model of the lung parenchyma as relevant in SARS-CoV-2 research.


Asunto(s)
Dependovirus/genética , Terapia Genética/métodos , Células Madre Embrionarias Humanas/citología , Enfermedades Pulmonares/terapia , Organoides/citología , Línea Celular , Dependovirus/inmunología , Técnicas de Transferencia de Gen , Vectores Genéticos/genética , Humanos , Pulmón/metabolismo , Modelos Biológicos , Tejido Parenquimatoso/citología
10.
Nat Commun ; 11(1): 4939, 2020 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-33009390

RESUMEN

Acoustic communication is enabled by the evolution of specialised hearing and sound producing organs. In this study, we performed a large-scale macroevolutionary study to understand how both hearing and sound production evolved and affected diversification in the insect order Orthoptera, which includes many familiar singing insects, such as crickets, katydids, and grasshoppers. Using phylogenomic data, we firmly establish phylogenetic relationships among the major lineages and divergence time estimates within Orthoptera, as well as the lineage-specific and dynamic patterns of evolution for hearing and sound producing organs. In the suborder Ensifera, we infer that forewing-based stridulation and tibial tympanal ears co-evolved, but in the suborder Caelifera, abdominal tympanal ears first evolved in a non-sexual context, and later co-opted for sexual signalling when sound producing organs evolved. However, we find little evidence that the evolution of hearing and sound producing organs increased diversification rates in those lineages with known acoustic communication.


Asunto(s)
Acústica , Evolución Biológica , Saltamontes/clasificación , Saltamontes/genética , Filogenia , Vocalización Animal , Animales , Teorema de Bayes , Genoma Mitocondrial , Saltamontes/anatomía & histología , Audición/fisiología , Modelos Biológicos , Sonido , Factores de Tiempo , Transcriptoma/genética
11.
Nat Commun ; 11(1): 5338, 2020 10 21.
Artículo en Inglés | MEDLINE | ID: mdl-33087703

RESUMEN

Tumor heterogeneity is a major cause of therapeutic resistance. Immunotherapy may exploit alternative vulnerabilities of drug-resistant cells, where tumor-specific human leukocyte antigen (HLA) peptide ligands are promising leads to invoke targeted anti-tumor responses. Here, we investigate the variability in HLA class I peptide presentation between different clonal cells of the same colorectal cancer patient, using an organoid system. While clone-specific differences in HLA peptide presentation were observed, broad inter-clone variability was even more prevalent (15-25%). By coupling organoid proteomics and HLA peptide ligandomics, we also found that tumor-specific ligands from DNA damage control and tumor suppressor source proteins were prominently presented by tumor cells, coinciding likely with the silencing of such cytoprotective functions. Collectively, these data illustrate the heterogeneous HLA peptide presentation landscape even within one individual, and hint that a multi-peptide vaccination approach against highly conserved tumor suppressors may be a viable option in patients with low tumor-mutational burden.


Asunto(s)
Neoplasias Colorrectales/inmunología , Antígenos HLA/metabolismo , Organoides/inmunología , Presentación de Antígeno , Línea Celular Tumoral , Células Clonales/inmunología , Células Clonales/metabolismo , Células Clonales/patología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Humanos , Ligandos , Modelos Biológicos , Proteínas de Neoplasias/metabolismo , Organoides/metabolismo , Organoides/patología , Proteoma/metabolismo , Transducción de Señal , Análisis de la Célula Individual , Serina-Treonina Quinasas TOR/metabolismo
12.
Nat Commun ; 11(1): 5365, 2020 10 23.
Artículo en Inglés | MEDLINE | ID: mdl-33097711

RESUMEN

Whereas self-propelled hard discs undergo motility-induced phase separation, self-propelled rods exhibit a variety of nonequilibrium phenomena, including clustering, collective motion, and spatio-temporal chaos. In this work, we present a theoretical framework representing active particles by continuum fields. This concept combines the simplicity of alignment-based models, enabling analytical studies, and realistic models that incorporate the shape of self-propelled objects explicitly. By varying particle shape from circular to ellipsoidal, we show how nonequilibrium stresses acting among self-propelled rods destabilize motility-induced phase separation and facilitate orientational ordering, thereby connecting the realms of scalar and vectorial active matter. Though the interaction potential is strictly apolar, both, polar and nematic order may emerge and even coexist. Accordingly, the symmetry of ordered states is a dynamical property in active matter. The presented framework may represent various systems including bacterial colonies, cytoskeletal extracts, or shaken granular media.


Asunto(s)
Fenómenos Fisiológicos Bacterianos , Movimiento (Física) , Análisis por Conglomerados , Simulación por Computador , Modelos Biológicos , Modelos Teóricos , Movimiento/fisiología , Termodinámica
13.
Nat Commun ; 11(1): 5375, 2020 10 23.
Artículo en Inglés | MEDLINE | ID: mdl-33097736

RESUMEN

Eutrophication is a widespread environmental change that usually reduces the stabilizing effect of plant diversity on productivity in local communities. Whether this effect is scale dependent remains to be elucidated. Here, we determine the relationship between plant diversity and temporal stability of productivity for 243 plant communities from 42 grasslands across the globe and quantify the effect of chronic fertilization on these relationships. Unfertilized local communities with more plant species exhibit greater asynchronous dynamics among species in response to natural environmental fluctuations, resulting in greater local stability (alpha stability). Moreover, neighborhood communities that have greater spatial variation in plant species composition within sites (higher beta diversity) have greater spatial asynchrony of productivity among communities, resulting in greater stability at the larger scale (gamma stability). Importantly, fertilization consistently weakens the contribution of plant diversity to both of these stabilizing mechanisms, thus diminishing the positive effect of biodiversity on stability at differing spatial scales. Our findings suggest that preserving grassland functional stability requires conservation of plant diversity within and among ecological communities.


Asunto(s)
Biota , Ecosistema , Eutrofización , Pradera , Biodiversidad , Biomasa , Fertilización , Modelos Biológicos , Plantas
14.
Clin Microbiol Rev ; 34(1)2020 12 16.
Artículo en Inglés | MEDLINE | ID: mdl-33115724

RESUMEN

Since the beginning of the COVID-19 pandemic, there has been intense debate over SARS-CoV-2's mode of transmission and appropriate personal protective equipment for health care workers in low-risk settings. The objective of this review is to identify and appraise the available evidence (clinical trials and laboratory studies on masks and respirators, epidemiological studies, and air sampling studies), clarify key concepts and necessary conditions for airborne transmission, and shed light on knowledge gaps in the field. We find that, except for aerosol-generating procedures, the overall data in support of airborne transmission-taken in its traditional definition (long-distance and respirable aerosols)-are weak, based predominantly on indirect and experimental rather than clinical or epidemiological evidence. Consequently, we propose a revised and broader definition of "airborne," going beyond the current droplet and aerosol dichotomy and involving short-range inhalable particles, supported by data targeting the nose as the main viral receptor site. This new model better explains clinical observations, especially in the context of close and prolonged contacts between health care workers and patients, and reconciles seemingly contradictory data in the SARS-CoV-2 literature. The model also carries important implications for personal protective equipment and environmental controls, such as ventilation, in health care settings. However, further studies, especially clinical trials, are needed to complete the picture.


Asunto(s)
Aerosoles/análisis , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/transmisión , Control de Infecciones/métodos , Pandemias/prevención & control , Material Particulado/análisis , Equipo de Protección Personal/provisión & distribución , Neumonía Viral/prevención & control , Neumonía Viral/transmisión , Betacoronavirus , Infección Hospitalaria/prevención & control , Infección Hospitalaria/transmisión , Personal de Salud/estadística & datos numéricos , Humanos , Modelos Biológicos , Ventilación
15.
Anticancer Res ; 40(11): 6179-6193, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33109555

RESUMEN

BACKGROUND: Growth factors and cytokines mediate complex interactions between cells within the breast tumour microenvironment. In advanced cancer, an excess of regulatory T (TREG) lymphocytes and lack of natural killer (NK) cells in tumour-infiltrating lymphocyte populations may reflect a shift to pro-tumorigenic adaptive immune mechanisms. To facilitate targeted assessment of the interactions between tumour and immune cells ex vivo, three-dimensional (3D) culture systems are able to better recapitulate the in vivo microenvironment, recreating the anatomy of tumours. MATERIALS AND METHODS: We used 3D breast tumour models to determine morphological alterations, and the levels of secreted transforming growth factor-ß (TGFß) and induced cytokines. 3D luminal phenotype models and basal phenotype models were generated by culturing NK cells and CD4+CD25+ TREG cells with MCF-7 cells and MDA-MB-231 cells respectively, in growth factor-reduced Matrigel. TGFß was qualitatively assessed by immunolocalisation and cytokine data from culture supernatant was acquired with a multiplex cytokine assay. Traditional statistical analysis and principal component analysis were employed to unravel the cytokine response. RESULTS AND CONCLUSION: We identified that an interleukin-6 (IL6)-chemokine axis associated with TGFß is primarily responsible for differences detected between breast cancer models, with luminal and basal phenotype tumours responding differentially to immune mediation. Identified cytokines are implicated in facilitating tumour cell subversion of immune cell function to promote an invasive phenotype. Moreover, the disruption of the extracellular matrix and failure to form well-differentiated tumour masses/networks is indicative of enhanced malignancy. Tumour cells are implicated in promoting a pro-inflammatory microenvironment to attenuate NK cell function and in inducing a pro-tumorigenic profile that is facilitated by TREG lymphocytes.


Asunto(s)
Neoplasias de la Mama/patología , Técnicas de Cultivo de Célula , Inflamación/patología , Modelos Biológicos , Forma de la Célula , Femenino , Humanos , Mediadores de Inflamación/metabolismo , Células MCF-7 , Análisis de Componente Principal , Factor de Crecimiento Transformador beta/metabolismo
16.
Med. U.P.B ; 39(2): 49-55, 21/10/2020.
Artículo en Español | LILACS, COLNAL | ID: biblio-1123581

RESUMEN

La aparición progresiva de habilidades sensoriales, motoras y cognitivo-afectivas en el humano a lo largo de su desarrollo es un reflejo de cambios fisiológicos que se gestan al interior del sistema nervioso. Dichos cambios hacen parte de procesos dinámicos y dependen, después del nacimiento, de la actividad eléctrica inducida por la experiencia. Considerando lo anterior, el sistema nervioso en desarrollo constituye una especie de protomapa, sobre el que la experiencia moldea características moleculares, neuroquímicas y de conectividad, que se reflejan en las actividades emergentes del sistema. La evidencia que soporta la importancia que la influencia experiencial tiene sobre el desarrollo del sistema nervioso viene en aumento. Esta revisión reúne información sobre estudios en modelos biológicos y en humanos sometidos a privación sensorial y ambiental. Se enfatiza en la caracterización de los rasgos cognitivos y sociales.


The progressive advent of sensory, motor, affective, and cognitive skills in the human being through its development, demonstrate physiological changes that are gestated within the nervous system. These processes are dynamic and dependent postnatally on electrical activity induced by experience. Taking this into account, the developing nervous system constitutes a protomap molded by experience dependent molecular, physiological and connectivity characteristics, which are reflected in the emergent principles of the system. The evidence that supports the importance of experience as influence over the development of this system has increased in the past years. This document gathers information about animal models and human studies enduring sensory and environmental deprivation, emphasizing in the characterization of their cognitive and social remarks.


O aparecimento progressivo de habilidades sensoriais, motoras e cognitivo-afetivas no humano ao longo do seu desenvolvimento é um reflexo de mudanças fisiológicas que se gestam no interior do sistema nervoso. Ditas mudanças fazem parte de processos dinâmicos e dependem, depois do nascimento, da atividade elétrica induzida pela experiência. Considerando o anterior, o sistema nervoso em desenvolvimento constitui uma espécie de "protomapa", sobre o que a experiência molda características moleculares, neuroquímicas e de conectividade, que se refletem nas atividades emergentes do sistema. A evidência que suporta a importância que a influência experiencial tem sobre o desenvolvimento do sistema nervoso vem em aumento. Esta revisão reúne informação sobre estudos em modelos biológicos e em humanos submetidos a privação sensorial e ambiental. Se enfatiza na caracterização das características cognitivas e sociais.


Asunto(s)
Humanos , Animales , Recién Nacido , Lactante , Preescolar , Niño , Adolescente , Adulto , Trastornos del Neurodesarrollo , Reflejo , Privación Sensorial , Sinapsis , Cognición , Modelos Animales , Crecimiento y Desarrollo , Modelos Biológicos , Sistema Nervioso , Plasticidad Neuronal
17.
Nat Commun ; 11(1): 4956, 2020 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-33009383

RESUMEN

Tet-enzyme-mediated 5-hydroxymethylation of cytosines in DNA plays a crucial role in mouse embryonic stem cells (ESCs). In RNA also, 5-hydroxymethylcytosine (5hmC) has recently been evidenced, but its physiological roles are still largely unknown. Here we show the contribution and function of this mark in mouse ESCs and differentiating embryoid bodies. Transcriptome-wide mapping in ESCs reveals hundreds of messenger RNAs marked by 5hmC at sites characterized by a defined unique consensus sequence and particular features. During differentiation a large number of transcripts, including many encoding key pluripotency-related factors (such as Eed and Jarid2), show decreased cytosine hydroxymethylation. Using Tet-knockout ESCs, we find Tet enzymes to be partly responsible for deposition of 5hmC in mRNA. A transcriptome-wide search further reveals mRNA targets to which Tet1 and Tet2 bind, at sites showing a topology similar to that of 5hmC sites. Tet-mediated RNA hydroxymethylation is found to reduce the stability of crucial pluripotency-promoting transcripts. We propose that RNA cytosine 5-hydroxymethylation by Tets is a mark of transcriptome flexibility, inextricably linked to the balance between pluripotency and lineage commitment.


Asunto(s)
5-Metilcitosina/análogos & derivados , Diferenciación Celular , Proteínas de Unión al ADN/metabolismo , Células Madre Embrionarias de Ratones/citología , Células Madre Embrionarias de Ratones/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , ARN/metabolismo , 5-Metilcitosina/metabolismo , Animales , Especificidad de Anticuerpos/inmunología , Secuencia de Bases , Cuerpos Embrioides/metabolismo , Ratones , Modelos Biológicos , Células Madre Pluripotentes/metabolismo , Unión Proteica , Estabilidad del ARN/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transcriptoma/genética
18.
Nat Commun ; 11(1): 4958, 2020 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-33009395

RESUMEN

Striatal dopamine (DA) is critical for action and learning. Recent data show that DA release is under tonic inhibition by striatal GABA. Ambient striatal GABA tone on striatal projection neurons can be determined by plasma membrane GABA uptake transporters (GATs) located on astrocytes and neurons. However, whether striatal GATs and astrocytes determine DA output are unknown. We reveal that DA release in mouse dorsolateral striatum, but not nucleus accumbens core, is governed by GAT-1 and GAT-3. These GATs are partly localized to astrocytes, and are enriched in dorsolateral striatum compared to accumbens core. In a mouse model of early parkinsonism, GATs are downregulated, tonic GABAergic inhibition of DA release augmented, and nigrostriatal GABA co-release attenuated. These data define previously unappreciated and important roles for GATs and astrocytes in supporting DA release in striatum, and reveal a maladaptive plasticity in early parkinsonism that impairs DA output in vulnerable striatal regions.


Asunto(s)
Cuerpo Estriado/metabolismo , Dopamina/metabolismo , Regulación hacia Abajo , Proteínas Transportadoras de GABA en la Membrana Plasmática/metabolismo , Trastornos Parkinsonianos/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Animales , Astrocitos/metabolismo , Membrana Celular/metabolismo , Modelos Animales de Enfermedad , Glutamato Descarboxilasa/metabolismo , Ratones Endogámicos C57BL , Modelos Biológicos , Núcleo Accumbens/metabolismo
19.
Nat Commun ; 11(1): 5073, 2020 10 08.
Artículo en Inglés | MEDLINE | ID: mdl-33033238

RESUMEN

Brain cells continuously produce and release protons into the extracellular space, with the rate of acid production corresponding to the levels of neuronal activity and metabolism. Efficient buffering and removal of excess H+ is essential for brain function, not least because all the electrogenic and biochemical machinery of synaptic transmission is highly sensitive to changes in pH. Here, we describe an astroglial mechanism that contributes to the protection of the brain milieu from acidification. In vivo and in vitro experiments conducted in rodent models show that at least one third of all astrocytes release bicarbonate to buffer extracellular H+ loads associated with increases in neuronal activity. The underlying signalling mechanism involves activity-dependent release of ATP triggering bicarbonate secretion by astrocytes via activation of metabotropic P2Y1 receptors, recruitment of phospholipase C, release of Ca2+ from the internal stores, and facilitated outward HCO3- transport by the electrogenic sodium bicarbonate cotransporter 1, NBCe1. These results show that astrocytes maintain local brain extracellular pH homeostasis via a neuronal activity-dependent release of bicarbonate. The data provide evidence of another important metabolic housekeeping function of these glial cells.


Asunto(s)
Astrocitos/metabolismo , Bicarbonatos/metabolismo , Encéfalo/metabolismo , Espacio Extracelular/metabolismo , Acetazolamida/farmacología , Adenosina Trifosfato/metabolismo , Animales , Astrocitos/efectos de los fármacos , Anhidrasas Carbónicas/metabolismo , Células Cultivadas , Estimulación Eléctrica , Fluorescencia , Hipocampo/metabolismo , Concentración de Iones de Hidrógeno , Ratones Endogámicos C57BL , Modelos Biológicos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Antagonistas Purinérgicos/farmacología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Sprague-Dawley , Receptores Purinérgicos/metabolismo , Transducción de Señal , Simportadores de Sodio-Bicarbonato/metabolismo
20.
Nat Commun ; 11(1): 5065, 2020 10 08.
Artículo en Inglés | MEDLINE | ID: mdl-33033237

RESUMEN

The type VI protein secretion system (T6SS) is a powerful needle-like machinery found in Gram-negative bacteria that can penetrate the cytosol of receiving cells in milliseconds by physical force. Anchored by its membrane-spanning complex (MC) and a baseplate (BP), the T6SS sheath-tube is assembled in a stepwise process primed by TssA and terminated by TagA. However, the molecular details of its assembly remain elusive. Here, we systematically examined the initiation and termination of contractile and non-contractile T6SS sheaths in MC-BP, tssA and tagA mutants by fluorescence microscopy. We observe long pole-to-pole sheath-tube structures in the non-contractile MC-BP defective mutants but not in the Hcp tube or VgrG spike mutants. Combining overexpression and genetic mutation data, we demonstrate complex effects of TssM, TssA and TagA interactions on T6SS sheath-tube dynamics. We also report promiscuous interactions of TagA with multiple T6SS components, similar to TssA. Our results demonstrate that priming of the T6SS sheath-tube assembly is not dependent on TssA, nor is the assembly termination dependent on the distal end TssA-TagA interaction, and highlight the tripartite control of TssA-TssM-TagA on sheath-tube initiation and termination.


Asunto(s)
Proteínas Bacterianas/metabolismo , Sistemas de Secreción Tipo VI/metabolismo , Vibrio cholerae/metabolismo , Proteínas Bacterianas/química , Membrana Celular/metabolismo , Escherichia coli/metabolismo , Proteínas Fluorescentes Verdes/metabolismo , Proteínas de la Membrana/metabolismo , Viabilidad Microbiana , Modelos Biológicos , Mutación/genética , Unión Proteica , Dominios Proteicos
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