Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 44.735
Filtrar
1.
Rev. bioét. derecho ; (50): 425-438, nov. 2020.
Artigo em Espanhol | IBECS | ID: ibc-191366

RESUMO

La crisis sanitaria global que es la COVID-19 arroja al pensamiento hacia lugares incómodos. En el presente manuscrito sugiero que la filosofía pospandémica, de ahora en adelante, no puede ni podrá desentenderse del fenómeno de lo viviente, específicamente del viviente animal no humano. Precisamente, producto de la indiferencia de la cuestión animal, la filosofía ha creído por pretérita la tesis cartesiana del animal-máquina. Muy por el contrario, en este texto propongo que dicha comprensión del animal no tiene nada de arcaica, y que, provocada por el contexto pandémico, podría dar a lugar a lo que tentativamente es posible denominar "cartesianismo distópico". Ante esta consumación, cuya cristalización es el devenir (total) máquina del animal no humano, una bioética animal podría servir como vía para contravenir el cartesianismo distópico


The global health crisis that is the COVID-19 throws the thinking into uncomfortable places. In the present manuscript I suggest that post-pandemic philosophy, from now on, cannot and will not ignore the phenomenon of the living, specifically the living non-human animal. Precisely, as a result of the indifference of the animal question, philosophy has believed in the past the Cartesian thesis of the animal-machine. On the contrary, in this text we propose that such understanding of the animal is not archaic at all, and that, triggered by the pandemic context, could give rise to what can tentatively be called "dystopian Cartesianism". In front of this consummation, whose crystallization is the (total) machine becoming of the non-human animal, an animal bioethics could serve as a way to contravene the dystopian Cartesianism


La crisi sanitària global que és la COVID-19 llança el pensament cap a llocs incòmodes. En el present manuscrit suggereixo que la filosofia postpandèmica, d'ara endavant, no es pot ni es podrà desentendre del fenòmen del que és viu, específicament del vivent animal no humà. Precisament, producte de la indiferència de la qüestió animal, la filosofia ha cregut per pretèrita la tesi cartesiana de l'animal-màquina. Molt al contrari, en aquest text proposo que aquesta comprensió de l'animal no té res d'arcaica, I que, provocada pel context pandèmic, podria donar a lloc al que temptativament és possible anomenar "cartesianisme distòpic". Davant d'aquesta consumació, la cristal·lització del qual és l'esdevenir (total) màquina de l'animal no humà, una bioètica animal podria servir com a via per contravenir el cartesianisme distòpic


Assuntos
Humanos , Animais , Temas Bioéticos , Modelos Animais , Experimentação Animal/ética , Animais Domésticos , Infecções por Coronavirus , Pandemias , Comitês de Cuidado Animal
2.
Rev Col Bras Cir ; 47: e20202530, 2020 Sep 04.
Artigo em Inglês, Português | MEDLINE | ID: mdl-32901707

RESUMO

INTRODUCTION: simulation based teaching is a powerful tool in medical education, allowing hands on practice under a controlled environment and with repeated maneuvers. Central venous access venipuncture is one of the most frequent procedures carried out in the hospital setting, due to its various clinical indications and, when performed with the help of ultrasonography, the risk of adverse events is minimized. Aim: to develop, to describe and to test a porcine model that simulates the central venous access puncture aided by ultrasonography. METHOD: a low cost porcine model was developed to train medical students and residents on central venous access guided by ultrasonography. Both students and medical residents underwent a theoretical training regarding the model, followed by a hands-on training session. Afterwards, the participants assessed the model by answering a questionnaire. RESULTS: there were 51 participants. The average score regarding the similarity between the model and the human anatomy was 9.15. When the characteristics were separately assessed, the mean scores regarding the similarity of the vessels, anatomic disposition and ultrasonographic characteristics as well as the venipuncture were, respectively, 9.27; 9.31; 9.54 and 8.86. CONCLUSION: The model was approved and considered appropriate for the training of central venous venipuncture by all the participants. Furthermore, it is a low cost, simple and reproducible model, that presents high similarity with the human anatomy. Therefore, it may be used as an aid to train people on ultrasonography guided central venous access.


Assuntos
Cateteres Venosos Centrais , Educação Médica , Treinamento por Simulação , Estudantes de Medicina/psicologia , Ultrassonografia de Intervenção/métodos , Animais , Humanos , Modelos Animais , Suínos
3.
Nat Commun ; 11(1): 4686, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32943633

RESUMO

Electrophysiology provides a direct readout of neuronal activity at a temporal precision only limited by the sampling rate. However, interrogating deep brain structures, implanting multiple targets or aiming at unusual angles still poses significant challenges for operators, and errors are only discovered by post-hoc histological reconstruction. Here, we propose a method combining the high-resolution information about bone landmarks provided by micro-CT scanning with the soft tissue contrast of the MRI, which allowed us to precisely localize electrodes and optic fibers in mice in vivo. This enables arbitrating the success of implantation directly after surgery with a precision comparable to gold standard histology. Adjustment of the recording depth with micro-drives or early termination of unsuccessful experiments saves many working hours, and fast 3-dimensional feedback helps surgeons avoid systematic errors. Increased aiming precision enables more precise targeting of small or deep brain nuclei and multiple targeting of specific cortical or hippocampal layers.


Assuntos
Encéfalo/diagnóstico por imagem , Eletrodos Implantados , Processamento de Imagem Assistida por Computador/métodos , Fibras Ópticas , Microtomografia por Raio-X/métodos , Animais , Comportamento Animal , Encéfalo/patologia , Mapeamento Encefálico , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Hipocampo/cirurgia , Técnicas Histológicas/métodos , Imagem por Ressonância Magnética/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Silício , Técnicas Estereotáxicas
5.
Nat Commun ; 11(1): 4687, 2020 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948771

RESUMO

Chemical biology strategies for directly perturbing protein homeostasis including the degradation tag (dTAG) system provide temporal advantages over genetic approaches and improved selectivity over small molecule inhibitors. We describe dTAGV-1, an exclusively selective VHL-recruiting dTAG molecule, to rapidly degrade FKBP12F36V-tagged proteins. dTAGV-1 overcomes a limitation of previously reported CRBN-recruiting dTAG molecules to degrade recalcitrant oncogenes, supports combination degrader studies and facilitates investigations of protein function in cells and mice.


Assuntos
Peptídeo Hidrolases/metabolismo , Proteínas/metabolismo , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Animais , Feminino , Técnicas de Inativação de Genes , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos Knockout , Modelos Animais , Proteômica , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteína 1A de Ligação a Tacrolimo/genética , Proteína 1A de Ligação a Tacrolimo/metabolismo , Proteínas de Ligação a Tacrolimo , Proteína Supressora de Tumor Von Hippel-Lindau/genética
7.
Viruses ; 12(9)2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32916958

RESUMO

BACKGROUND: To prioritize the development of antiviral compounds, it is necessary to compare their relative preclinical activity and clinical efficacy. METHODS: We reviewed in vitro, animal model, and clinical studies of candidate anti-coronavirus compounds and placed extracted data in an online relational database. RESULTS: As of August 2020, the Coronavirus Antiviral Research Database (CoV-RDB; covdb.stanford.edu) contained over 2800 cell culture, entry assay, and biochemical experiments, 259 animal model studies, and 73 clinical studies from over 400 published papers. SARS-CoV-2, SARS-CoV, and MERS-CoV account for 85% of the data. Approximately 75% of experiments involved compounds with known or likely mechanisms of action, including monoclonal antibodies and receptor binding inhibitors (21%), viral protease inhibitors (17%), miscellaneous host-acting inhibitors (10%), polymerase inhibitors (9%), interferons (7%), fusion inhibitors (5%), and host protease inhibitors (5%). Of 975 compounds with known or likely mechanism, 135 (14%) are licensed in the U.S. for other indications, 197 (20%) are licensed outside the U.S. or are in human trials, and 595 (61%) are pre-clinical investigational compounds. CONCLUSION: CoV-RDB facilitates comparisons between different candidate antiviral compounds, thereby helping scientists, clinical investigators, public health officials, and funding agencies prioritize the most promising compounds and repurposed drugs for further development.


Assuntos
Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Bases de Dados Factuais , Pneumonia Viral/tratamento farmacológico , Animais , Antivirais/uso terapêutico , Células Cultivadas , Ensaios Clínicos como Assunto , Coronavirus/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Humanos , Mamíferos , Modelos Animais , Pandemias , Sistema de Registros , Especificidade da Espécie , Interface Usuário-Computador
8.
Toxins (Basel) ; 12(9)2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32957454

RESUMO

The deadly pandemic named COVID-19, caused by a new coronavirus (SARS-CoV-2), emerged in 2019 and is still spreading globally at a dangerous pace. As of today, there are no proven vaccines, therapies, or even strategies to fight off this virus. Here, we describe the in silico docking results of a novel broad range anti-infective fusion protein RTAM-PAP1 against the various key proteins of SARS-CoV-2 using the latest protein-ligand docking software. RTAM-PAP1 was compared against the SARS-CoV-2 B38 antibody, ricin A chain, a pokeweed antiviral protein from leaves, and the lectin griffithsin using the special CoDockPP COVID-19 version. These experiments revealed novel binding mechanisms of RTAM-PAP1 with a high affinity to numerous SARS-CoV-2 key proteins. RTAM-PAP1 was further characterized in a preliminary toxicity study in mice and was found to be a potential therapeutic candidate. These findings might lead to the discovery of novel SARS-CoV-2 targets and therapeutic protein structures with outstanding functions.


Assuntos
Antivirais/química , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Ligação Proteica/efeitos dos fármacos , Proteínas Inativadoras de Ribossomos Tipo 1/química , Proteínas Inativadoras de Ribossomos Tipo 1/uso terapêutico , Ricina/uso terapêutico , Animais , Simulação por Computador , Humanos , Camundongos , Modelos Animais , Pandemias , Phytolacca americana/química , Folhas de Planta/química , Proteínas Inativadoras de Ribossomos Tipo 1/genética
9.
Plast Reconstr Surg ; 146(4): 792-798, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32970001

RESUMO

BACKGROUND: Tissue expansion relies on the ability of skin to grow in response to sustained mechanical strain. This study focuses on correlation of cellular and histologic changes with skin growth and deformation during tissue expansion. METHODS: Tissue expanders were placed underneath the skin of five Yucatan minipigs and inflated with one fill of 60 cc of saline 1 hour, 24 hours, 3 days, and 7 days before the animals were killed, or two fills of either 30 cc or 60 cc at 10 and 3 days or 14 and 7 days before the animals were killed. Skin biopsy specimens and three-dimensional photographs were used to calculate skin growth and stretch according to the authors' novel finite element analysis model. RESULTS: The mitotic index of keratinocytes in the basal layer increased 1 hour after stimulus was applied (4 percent) (p = 0.022), peaked at approximately day 3 (26 percent) (p < 0.0001), and tapered by day 7 (12.5 percent) (p = 0.012) after tissue expansion. The authors demonstrated that it is the volume per fill rather than the total volume in the expander that scales the magnitude of response. Lastly, the authors demonstrated that the ratio of deformation attributable to growth versus stretch (Fgrowth/Fstretch) after 60 cc of tissue expansion fill was 1.03 at 1 hour, 0.82 at 1 day, 0.85 at day 3, and 0.95 at 7 days. CONCLUSIONS: Peak cell proliferation occurred 3 days after tissue expansion fill and is scaled in response to stimulus magnitude. The growth component of deformation equilibrates to the stretch component at day 7, as cell proliferation has started to translate to skin growth.


Assuntos
Modelos Estatísticos , Pele/crescimento & desenvolvimento , Expansão de Tecido/métodos , Animais , Feminino , Modelos Animais , Tamanho do Órgão , Pele/anatomia & histologia , Suínos , Porco Miniatura , Fatores de Tempo
10.
Nat Commun ; 11(1): 4854, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32978383

RESUMO

Chronic imaging of neuronal networks in vitro has provided fundamental insights into mechanisms underlying neuronal function. Current labeling and optical imaging methods, however, cannot be used for continuous and long-term recordings of the dynamics and evolution of neuronal networks, as fluorescent indicators can cause phototoxicity. Here, we introduce a versatile platform for label-free, comprehensive and detailed electrophysiological live-cell imaging of various neurogenic cells and tissues over extended time scales. We report on a dual-mode high-density microelectrode array, which can simultaneously record in (i) full-frame mode with 19,584 recording sites and (ii) high-signal-to-noise mode with 246 channels. We set out to demonstrate the capabilities of this platform with recordings from primary and iPSC-derived neuronal cultures and tissue preparations over several weeks, providing detailed morpho-electrical phenotypic parameters at subcellular, cellular and network level. Moreover, we develop reliable analysis tools, which drastically increase the throughput to infer axonal morphology and conduction speed.


Assuntos
Rede Nervosa/fisiologia , Neurônios/fisiologia , Imagem Óptica/métodos , Análise de Célula Única/métodos , Animais , Axônios , Encéfalo , Células Cultivadas , Células-Tronco Pluripotentes Induzidas , Camundongos , Microeletrodos , Modelos Animais , Rede Nervosa/diagnóstico por imagem , Imagem Óptica/instrumentação , Ratos , Ratos Wistar , Gravação em Vídeo
11.
J Am Heart Assoc ; 9(18): e017368, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32896206

RESUMO

E-cigarette or vaping product use-associated lung injury was recognized in the United States in the summer of 2019 and is typified by acute respiratory distress, shortness of breath, chest pain, cough, and fever, associated with vaping. It can mimic many of the manifestations of coronavirus disease 2019 (COVID-19). Some investigators have suggested that E-cigarette or vaping product use-associated lung injury was due to tetrahydrocannabinol or vitamin E acetate oil mixed with the electronic cigarette liquid. In experimental rodent studies initially designed to study the effect of electronic cigarette use on the cardiovascular system, we observed an E-cigarette or vaping product use-associated lung injury-like condition that occurred acutely after use of a nichrome heating element at high power, without the use of tetrahydrocannabinol, vitamin E, or nicotine. Lung lesions included thickening of the alveolar wall with foci of inflammation, red blood cell congestion, obliteration of alveolar spaces, and pneumonitis in some cases; bronchi showed accumulation of fibrin, inflammatory cells, and mucus plugs. Electronic cigarette users should be cautioned about the potential danger of operating electronic cigarette units at high settings; the possibility that certain heating elements may be deleterious; and that E-cigarette or vaping product use-associated lung injury may not be dependent upon tetrahydrocannabinol, vitamin E, or nicotine.


Assuntos
Dronabinol/toxicidade , Vapor do Cigarro Eletrônico/toxicidade , Sistemas Eletrônicos de Liberação de Nicotina , Lesão Pulmonar/induzido quimicamente , Pulmão/efeitos dos fármacos , Pneumonia/induzido quimicamente , Vaping/efeitos adversos , Vitamina E/toxicidade , Animais , Exposição por Inalação , Pulmão/patologia , Lesão Pulmonar/patologia , Modelos Animais , Óleos , Pneumonia/patologia , Ratos , Medição de Risco
12.
Nat Commun ; 11(1): 4496, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32901024

RESUMO

Aging is characterized by the loss of homeostasis and the general decline of physiological functions, accompanied by various degenerative diseases and increased rates of mortality. Aging targeting small molecule screens have been performed many times, however, few have focused on endogenous metabolic intermediates-metabolites. Here, using C. elegans lifespan assays, we conducted a worm metabolite screen and identified an eukaryotes conserved metabolite, myo-inositol (MI), to extend lifespan, increase mobility and reduce fat content. Genetic analysis of enzymes in MI metabolic pathway suggest that MI alleviates aging through its derivative PI(4,5)P2. MI and PI(4,5)P2 are precursors of PI(3,4,5)P3, which is negatively related to longevity. The longevity effect of MI is dependent on the tumor suppressor gene, daf-18 (homologous to mouse Pten), independent of its classical pathway downstream genes, akt or daf-16. Furthermore, we found MI effects on aging and lifespan act through mitophagy regulator PTEN induced kinase-1 (pink-1) and mitophagy. MI's anti-aging effect is also conserved in mouse, indicating a conserved mechanism in mammals.


Assuntos
Envelhecimento/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Inositol/metabolismo , Longevidade/fisiologia , PTEN Fosfo-Hidrolase/metabolismo , Envelhecimento/efeitos dos fármacos , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Linhagem Celular Tumoral , Feminino , Fatores de Transcrição Forkhead/genética , Inositol/administração & dosagem , Locomoção/fisiologia , Longevidade/efeitos dos fármacos , Redes e Vias Metabólicas/genética , Metabolômica , Camundongos , Mitofagia/fisiologia , Modelos Animais , Fosfatos de Fosfatidilinositol/metabolismo , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Interferência de RNA , RNA-Seq
13.
Nat Commun ; 11(1): 4550, 2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32917862

RESUMO

Place cells exhibit spatially selective firing fields that collectively map the continuum of positions in environments; how such activity pattern develops with experience is largely unknown. Here, we record putative granule cells (GCs) and mossy cells (MCs) from the dentate gyrus (DG) over 27 days as mice repetitively run through a sequence of objects fixed onto a treadmill belt. We observe a progressive transformation of GC spatial representations, from a sparse encoding of object locations and spatial patterns to increasingly more single, evenly dispersed place fields, while MCs show little transformation and preferentially encode object locations. A competitive learning model of the DG reproduces GC transformations via the progressive integration of landmark-vector cells and spatial inputs and requires MC-mediated feedforward inhibition to evenly distribute GC representations, suggesting that GCs slowly encode conjunctions of objects and spatial information via competitive learning, while MCs help homogenize GC spatial representations.


Assuntos
Fibras Musgosas Hipocampais/fisiologia , Células de Lugar/fisiologia , Aprendizagem Espacial/fisiologia , Potenciais de Ação/fisiologia , Animais , Eletrodos Implantados , Eletroencefalografia/instrumentação , Masculino , Camundongos , Modelos Animais , Técnicas Estereotáxicas/instrumentação
14.
Nat Commun ; 11(1): 4560, 2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32917899

RESUMO

The rhesus macaque is an important model species in several branches of science, including neuroscience, psychology, ethology, and medicine. The utility of the macaque model would be greatly enhanced by the ability to precisely measure behavior in freely moving conditions. Existing approaches do not provide sufficient tracking. Here, we describe OpenMonkeyStudio, a deep learning-based markerless motion capture system for estimating 3D pose in freely moving macaques in large unconstrained environments. Our system makes use of 62 machine vision cameras that encircle an open 2.45 m × 2.45 m × 2.75 m enclosure. The resulting multiview image streams allow for data augmentation via 3D-reconstruction of annotated images to train a robust view-invariant deep neural network. This view invariance represents an important advance over previous markerless 2D tracking approaches, and allows fully automatic pose inference on unconstrained natural motion. We show that OpenMonkeyStudio can be used to accurately recognize actions and track social interactions.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Macaca mulatta/fisiologia , Movimento (Física) , Algoritmos , Animais , Fenômenos Biomecânicos , Aprendizado Profundo , Masculino , Modelos Animais , Movimento , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologia , Redes Neurais de Computação
15.
Nat Commun ; 11(1): 4559, 2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32917906

RESUMO

The temporal embryonic origins of cortical GABA neurons are critical for their specialization. In the neonatal hippocampus, GABA cells born the earliest (ebGABAs) operate as 'hubs' by orchestrating population synchrony. However, their adult fate remains largely unknown. To fill this gap, we have examined CA1 ebGABAs using a combination of electrophysiology, neurochemical analysis, optogenetic connectivity mapping as well as ex vivo and in vivo calcium imaging. We show that CA1 ebGABAs not only operate as hubs during development, but also maintain distinct morpho-physiological and connectivity profiles, including a bias for long-range targets and local excitatory inputs. In vivo, ebGABAs are activated during locomotion, correlate with CA1 cell assemblies and display high functional connectivity. Hence, ebGABAs are specified from birth to ensure unique functions throughout their lifetime. In the adult brain, this may take the form of a long-range hub role through the coordination of cell assemblies across distant regions.


Assuntos
Neurônios GABAérgicos/fisiologia , Hipocampo/fisiologia , Animais , Axônios , Encéfalo , Região CA1 Hipocampal/fisiologia , Feminino , Masculino , Camundongos , Modelos Animais , Vias Neurais/fisiologia , Optogenética , Sinapses/fisiologia
16.
Nat Commun ; 11(1): 4816, 2020 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-32968047

RESUMO

Understanding cell types and mechanisms of dental growth is essential for reconstruction and engineering of teeth. Therefore, we investigated cellular composition of growing and non-growing mouse and human teeth. As a result, we report an unappreciated cellular complexity of the continuously-growing mouse incisor, which suggests a coherent model of cell dynamics enabling unarrested growth. This model relies on spatially-restricted stem, progenitor and differentiated populations in the epithelial and mesenchymal compartments underlying the coordinated expansion of two major branches of pulpal cells and diverse epithelial subtypes. Further comparisons of human and mouse teeth yield both parallelisms and differences in tissue heterogeneity and highlight the specifics behind growing and non-growing modes. Despite being similar at a coarse level, mouse and human teeth reveal molecular differences and species-specific cell subtypes suggesting possible evolutionary divergence. Overall, here we provide an atlas of human and mouse teeth with a focus on growth and differentiation.


Assuntos
Diferenciação Celular , Células-Tronco/citologia , Dente/citologia , Dente/crescimento & desenvolvimento , Adolescente , Adulto , Animais , Diferenciação Celular/genética , Células Epiteliais , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Heterogeneidade Genética , Humanos , Incisivo/citologia , Incisivo/crescimento & desenvolvimento , Masculino , Mesoderma/citologia , Mesoderma/crescimento & desenvolvimento , Mesoderma/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Dente Molar/citologia , Dente Molar/crescimento & desenvolvimento , Odontoblastos , Adulto Jovem
17.
Nat Commun ; 11(1): 4819, 2020 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-32968048

RESUMO

In many parts of the nervous system, experience-dependent refinement of neuronal circuits predominantly involves synapse elimination. The role of sleep in this process remains unknown. We investigated the role of sleep in experience-dependent dendritic spine elimination of layer 5 pyramidal neurons in the visual (V1) and frontal association cortex (FrA) of 1-month-old mice. We found that monocular deprivation (MD) or auditory-cued fear conditioning (FC) caused rapid spine elimination in V1 or FrA, respectively. MD- or FC-induced spine elimination was significantly reduced after total sleep or REM sleep deprivation. Total sleep or REM sleep deprivation also prevented MD- and FC-induced reduction of neuronal activity in response to visual or conditioned auditory stimuli. Furthermore, dendritic calcium spikes increased substantially during REM sleep, and the blockade of these calcium spikes prevented MD- and FC-induced spine elimination. These findings reveal an important role of REM sleep in experience-dependent synapse elimination and neuronal activity reduction.


Assuntos
Córtex Cerebral/fisiologia , Espinhas Dendríticas/fisiologia , Sono REM/fisiologia , Animais , Condicionamento Clássico , Medo/fisiologia , Camundongos , Camundongos Transgênicos , Modelos Animais , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Células Piramidais/fisiologia , Privação Sensorial/fisiologia , Privação do Sono , Sinapses , Córtex Visual/fisiologia
18.
Hear Res ; 395: 108019, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32768772

RESUMO

Hearing and balance deficits have been reported during and following treatment with the antimalarial drug chloroquine. However, experimental work examining the direct actions of chloroquine on mechanoreceptive hair cells in common experimental models is lacking. This study examines the effects of chloroquine on hair cells using two common experimental models: the zebrafish lateral line and neonatal mouse cochlear cultures. Zebrafish larvae were exposed to varying concentrations of chloroquine phosphate or hydroxychloroquine for 1 h or 24 h, and hair cells assessed by antibody staining. A significant, dose-dependent reduction in the number of surviving hair cells was seen across conditions for both exposure periods. Hydroxychloroquine showed similar toxicity. In mouse cochlear cultures, chloroquine damage was specific to outer hair cells in tissue from the cochlear basal turn, consistent with susceptibility to other ototoxic agents. These findings suggest a need for future studies employing hearing and balance monitoring during exposure to chloroquine and related compounds, particularly with interest in these compounds as therapeutics against viral infections including coronavirus.


Assuntos
Sobrevivência Celular/efeitos dos fármacos , Cloroquina/análogos & derivados , Células Ciliadas Auditivas/efeitos dos fármacos , Hidroxicloroquina/toxicidade , Sistema da Linha Lateral/efeitos dos fármacos , Animais , Antivirais/toxicidade , Células Cultivadas , Cloroquina/toxicidade , Células Ciliadas Auditivas/citologia , Larva/efeitos dos fármacos , Camundongos , Modelos Animais , Ototoxicidade , Peixe-Zebra
19.
Nat Commun ; 11(1): 4191, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32826892

RESUMO

The nascent field of bioelectronic medicine seeks to decode and modulate peripheral nervous system signals to obtain therapeutic control of targeted end organs and effectors. Current approaches rely heavily on electrode-based devices, but size scalability, material and microfabrication challenges, limited surgical accessibility, and the biomechanically dynamic implantation environment are significant impediments to developing and deploying peripheral interfacing technologies. Here, we present a microscale implantable device - the nanoclip - for chronic interfacing with fine peripheral nerves in small animal models that begins to meet these constraints. We demonstrate the capability to make stable, high signal-to-noise ratio recordings of behaviorally-linked nerve activity over multi-week timescales. In addition, we show that multi-channel, current-steering-based stimulation within the confines of the small device can achieve multi-dimensional control of a small nerve. These results highlight the potential of new microscale design and fabrication techniques for realizing viable devices for long-term peripheral interfacing.


Assuntos
Microeletrodos , Nervos Periféricos/fisiologia , Impressão Tridimensional , Animais , Engenharia Biomédica , Eletrodos Implantados , Potenciais Evocados , Tentilhões/fisiologia , Masculino , Microtecnologia , Modelos Animais , Nervos Periféricos/cirurgia , Razão Sinal-Ruído
20.
Nat Commun ; 11(1): 4195, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32826916

RESUMO

Realizing a clinical-grade electronic medicine for peripheral nerve disorders is challenging owing to the lack of rational material design that mimics the dynamic mechanical nature of peripheral nerves. Electronic medicine should be soft and stretchable, to feasibly allow autonomous mechanical nerve adaptation. Herein, we report a new type of neural interface platform, an adaptive self-healing electronic epineurium (A-SEE), which can form compressive stress-free and strain-insensitive electronics-nerve interfaces and enable facile biofluid-resistant self-locking owing to dynamic stress relaxation and water-proof self-bonding properties of intrinsically stretchable and self-healable insulating/conducting materials, respectively. Specifically, the A-SEE does not need to be sutured or glued when implanted, thereby significantly reducing complexity and the operation time of microneurosurgery. In addition, the autonomous mechanical adaptability of the A-SEE to peripheral nerves can significantly reduce the mechanical mismatch at electronics-nerve interfaces, which minimizes nerve compression-induced immune responses and device failure. Though a small amount of Ag leaked from the A-SEE is observed in vivo (17.03 ppm after 32 weeks of implantation), we successfully achieved a bidirectional neural signal recording and stimulation in a rat sciatic nerve model for 14 weeks. In view of our materials strategy and in vivo feasibility, the mechanically adaptive self-healing neural interface would be considered a new implantable platform for a wide range application of electronic medicine for neurological disorders in the human nervous system.


Assuntos
Eletrônica Médica/instrumentação , Eletrônica Médica/métodos , Neurocirurgia/instrumentação , Neurocirurgia/métodos , Nervos Periféricos/fisiologia , Animais , Engenharia Biomédica/instrumentação , Engenharia Biomédica/métodos , Sistema Nervoso Central/fisiologia , Sistema Nervoso Central/cirurgia , Ouro , Humanos , Masculino , Teste de Materiais , Modelos Animais , Tecido Nervoso/patologia , Tecido Nervoso/cirurgia , Nervos Periféricos/patologia , Nervos Periféricos/cirurgia , Polímeros/química , Próteses e Implantes , Ratos , Nervo Isquiático , Dispositivos Eletrônicos Vestíveis
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA