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1.
Nature ; 629(8013): 861-868, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38750353

RESUMEN

A central assumption of neuroscience is that long-term memories are represented by the same brain areas that encode sensory stimuli1. Neurons in inferotemporal (IT) cortex represent the sensory percept of visual objects using a distributed axis code2-4. Whether and how the same IT neural population represents the long-term memory of visual objects remains unclear. Here we examined how familiar faces are encoded in the IT anterior medial face patch (AM), perirhinal face patch (PR) and temporal pole face patch (TP). In AM and PR we observed that the encoding axis for familiar faces is rotated relative to that for unfamiliar faces at long latency; in TP this memory-related rotation was much weaker. Contrary to previous claims, the relative response magnitude to familiar versus unfamiliar faces was not a stable indicator of familiarity in any patch5-11. The mechanism underlying the memory-related axis change is likely intrinsic to IT cortex, because inactivation of PR did not affect axis change dynamics in AM. Overall, our results suggest that memories of familiar faces are represented in AM and perirhinal cortex by a distinct long-latency code, explaining how the same cell population can encode both the percept and memory of faces.


Asunto(s)
Reconocimiento en Psicología , Lóbulo Temporal , Lóbulo Temporal/fisiología , Lóbulo Temporal/citología , Masculino , Animales , Reconocimiento en Psicología/fisiología , Factores de Tiempo , Memoria a Largo Plazo/fisiología , Reconocimiento Facial/fisiología , Macaca mulatta , Corteza Perirrinal/fisiología , Corteza Perirrinal/citología , Neuronas/fisiología , Memoria/fisiología , Cara , Percepción Visual/fisiología , Femenino , Estimulación Luminosa
2.
J Hazard Mater ; 465: 133009, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38029587

RESUMEN

Heavy metal complexes in industrial wastewater are challenging to be removed by conventional methods arising from their stable chelating structure. In this study, zero-valent iron (ZVI) was ball-milled with tiny formic acid (FA), and the as-prepared sample (FA-ZVIbm) was attempted to eliminate a model heavy metal complex of Cu(II)-ethylenediaminetetraacetic acid (Cu(II)-EDTA). The addition of FA to ball-milling could dramatically enhance the performance of ball-milled ZVI (ZVIbm) towards Cu(II)-EDTA removal and increase the removal rate constant by 80 times. This conspicuous improvement of Cu(II)-EDTA elimination was attributed to the ferrous formate (Fe(HCOO)2) shell formed on the surface of FA-ZVIbm. Results revealed that the Fe(HCOO)2 shell facilitated the activation of O2 to reactive oxygen species (ROS) and the leaching of Fe3+. Cu(II)-EDTA was decomplexed through both oxidative destruction and Fe3+ replacement, and the released Cu2+ was reduced by FA-ZVIbm and immobilized synchronously. Meanwhile, the ligands underwent oxidative degradation by ROS, thus avoiding the re-chelation ecological risk. Impressively, FA-ZVIbm could achieve cyclic treatment of actual copper complex wastewater and possessed promising advantage in treatment cost. This study would offer a promising approach for eliminating Cu(II)-EDTA through EDTA ligands degradation and synchronous Cu(II) removal, moreover to shed light on the decomplexation mechanism.

3.
Biophys Chem ; 297: 107013, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37030215

RESUMEN

The constant mutation of SARS-CoV-2 has triggered a new round of public health crises and has had a huge impact on existing vaccines and diagnostic tools. It is essential to develop a new flexible method to distinguish mutations to prevent the spread of the virus. In this work, we used the combination of density functional theory (DFT) and non-equilibrium Green's function formulation with decoherence, to theoretically study the effect of viral mutation on charge transport properties of viral nucleic acid molecules. We found that all mutation of SARS-CoV-2 on spike protein was accompanied by the change of gene sequence conductance, this is attributed to the change of nucleic acid molecular energy level caused by mutation. Among them, the mutations L18F, P26S, and T1027I caused the largest conductance change after mutation. This provides a theoretical possibility for detecting virus mutation based on the change of molecular conductance of virus nucleic acid.


Asunto(s)
COVID-19 , Ácidos Nucleicos , Humanos , ARN , SARS-CoV-2/genética , Mutación , ADN
4.
Math Biosci Eng ; 20(2): 3504-3527, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36899591

RESUMEN

Deep learning has provided powerful support for person re-identification (person re-id) over the years, and superior performance has been achieved by state-of-the-art. While under practical application scenarios such as public monitoring, the cameras' resolutions are usually 720p, the captured pedestrian areas tend to be closer to 128×64 small pixel size. Research on person re-id at 128×64 small pixel size is limited by less effective pixel information. The frame image qualities are degraded and inter-frame information complementation requires a more careful selection of beneficial frames. Meanwhile, there are various large differences in person images, such as misalignment and image noise, which are harder to distinguish from person information at the small size, and eliminating a specific sub-variance is still not robust enough. The Person Feature Correction and Fusion Network (FCFNet) proposed in this paper introduces three sub-modules, which strive to extract discriminate video-level features from the perspectives of "using complementary valid information between frames" and "correcting large variances of person features". The inter-frame attention mechanism is introduced through frame quality assessment, guiding informative features to dominate the fusion process and generating a preliminary frame quality score to filter low-quality frames. Two other feature correction modules are fitted to optimize the model's ability to perceive information from small-sized images. The experiments on four benchmark datasets confirm the effectiveness of FCFNet.

5.
Artículo en Inglés | MEDLINE | ID: mdl-36361275

RESUMEN

Current healthcare is centered on the perception of people's health. The purpose of this study was to investigate the relationship between self-perceived health (physical, psychological, social, and environmental dimensions) and two main clinical symptoms (shoulder pain and restricted shoulder motion) in patients with frozen shoulders. A total of 49 patients diagnosed with frozen shoulders were recruited and divided into high- and low-disability groups according to the severity of their frozen shoulders. Participants were measured for shoulder passive range of motion, pain intensity, and self-perceived health, using a brief version of the World Health Organization Quality of Life questionnaire. The results showed that the high-disability group had poorer self-perceived health (lower quality of life scores) than the low-disability group (p < 0.05). There was no significant correlation between the quality of life scores and the two clinical symptoms in either the high- or low-disability group. Our findings revealed that the multidimensional self-perceived health of frozen shoulder patients could not be inferred from the severity of shoulder pain and restricted shoulder motions. This study suggests that healthcare providers should pay more attention to patients' self-perceived health needs while addressing the clinical symptoms in patients with frozen shoulders.


Asunto(s)
Bursitis , Articulación del Hombro , Humanos , Dolor de Hombro , Calidad de Vida , Hombro , Rango del Movimiento Articular
6.
J Interv Cardiol ; 2022: 1901139, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36082307

RESUMEN

The study aimed to investigate the efficacy and safety of coronary intervention via distal transradial access (dTRA) in patients with low body mass index (BMI). A total of 67 patients with low BMI who underwent coronary intervention, comprising 29 patients via dTRA and 38 patients via conventional transradial access (cTRA), were retrospectively included. There was no significant difference in the puncture success rate between the two groups (dTRA 96.6%, cTRA 97.4%, P=0.846). Compared with the cTRA group, the success rate of one-needle puncture in the dTRA group was lower (51.7% vs. 81.6%, P=0.020). The compression haemostasis time in the dTRA group was shorter than that in the cTRA group (P < 0.001). However, the incidence of radial artery occlusion was lower in the dTRA group than in the cTRA group (4.0% vs. 33.3%, P=0.007). In conclusion, coronary intervention via dTRA was safe and effective in patients with low BMI.


Asunto(s)
Índice de Masa Corporal , Intervención Coronaria Percutánea , Arteriopatías Oclusivas/epidemiología , Humanos , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/métodos , Punciones , Arteria Radial , Estudios Retrospectivos
7.
Proc Natl Acad Sci U S A ; 117(33): 20254-20264, 2020 08 18.
Artículo en Inglés | MEDLINE | ID: mdl-32747543

RESUMEN

Correlated activation of cortical neurons often occurs in the brain and repetitive correlated neuronal firing could cause long-term modifications of synaptic efficacy and intrinsic excitability. We found that repetitive optogenetic activation of neuronal populations in the mouse cortex caused enhancement of optogenetically evoked firing of local coactivated neurons as well as distant cortical neurons in both ipsilateral and contralateral hemispheres. This global enhancement of evoked responses required coactivation of a sufficiently large population of neurons either within one cortical area or distributed in several areas. Enhancement of neuronal firing was saturable after repeated episodes of coactivation, diminished by inhibition of N-methyl-d-aspartic acid receptors, and accompanied by elevated excitatory postsynaptic potentials, all consistent with activity-induced synaptic potentiation. Chemogenetic inhibition of neuronal activity of the thalamus decreased the enhancement effect, suggesting thalamic involvement. Thus, correlated excitation of large neuronal populations leads to global enhancement of neuronal excitability.


Asunto(s)
Potenciales de Acción/fisiología , Potenciales Postsinápticos Excitadores/fisiología , Plasticidad Neuronal/fisiología , Neuronas/fisiología , Animales , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina , Excitabilidad Cortical , Colorantes Fluorescentes , Masculino , Ratones , Red Nerviosa , Transmisión Sináptica/fisiología
8.
Nature ; 583(7814): 103-108, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32494012

RESUMEN

The inferotemporal (IT) cortex is responsible for object recognition, but it is unclear how the representation of visual objects is organized in this part of the brain. Areas that are selective for categories such as faces, bodies, and scenes have been found1-5, but large parts of IT cortex lack any known specialization, raising the question of what general principle governs IT organization. Here we used functional MRI, microstimulation, electrophysiology, and deep networks to investigate the organization of macaque IT cortex. We built a low-dimensional object space to describe general objects using a feedforward deep neural network trained on object classification6. Responses of IT cells to a large set of objects revealed that single IT cells project incoming objects onto specific axes of this space. Anatomically, cells were clustered into four networks according to the first two components of their preferred axes, forming a map of object space. This map was repeated across three hierarchical stages of increasing view invariance, and cells that comprised these maps collectively harboured sufficient coding capacity to approximately reconstruct objects. These results provide a unified picture of IT organization in which category-selective regions are part of a coarse map of object space whose dimensions can be extracted from a deep network.


Asunto(s)
Modelos Neurológicos , Percepción Espacial/fisiología , Lóbulo Temporal/citología , Lóbulo Temporal/fisiología , Animales , Estimulación Eléctrica , Macaca mulatta/fisiología , Imagen por Resonancia Magnética , Masculino , Vías Nerviosas/fisiología , Lóbulo Temporal/anatomía & histología
9.
Chin Med J (Engl) ; 132(12): 1406-1413, 2019 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-31205097

RESUMEN

BACKGROUND: The long-term predicted value of microvolt T-wave alternans (MTWA) for ventricular tachyarrhythmia in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) remains unclear. Our study explored the characteristics of MTWA and its prognostic value when combined with an electrophysiologic study (EPS) in patients with ARVC. METHODS: All patients underwent non-invasive MTWA examination with modified moving average (MMA) analysis and an EPS. A positive event was defined as the first occurrence of sudden cardiac death, documented sustained ventricular tachycardia (VT), ventricular fibrillation, or the administration of appropriate implantable cardioverter defibrillator therapy including shock or anti-tachycardia pacing. RESULTS: Thirty-five patients with ARVC (age 38.6 ±â€Š11.0 years; 28 males) with preserved left ventricular (LV) function were recruited. The maximal TWA value (MaxValt) was 17.0 (11.0-27.0) µV. Sustained VT was induced in 22 patients by the EPS. During a median follow-up of 99.9 ±â€Š7.7 months, 15 patients had positive clinical events. When inducible VT was combined with the MaxValt, the area under the curve improved from 0.739 to 0.797. The receiver operating characteristic curve showed that a MaxValt of 23.5 µV was the optimal cutoff value to identify positive events. The multivariate Cox regression model for survival showed that MTWA (MaxValt, hazard ratio [HR], 1.06; 95% confidence interval [CI], 1.01-1.11; P = 0.01) and inducible VT (HR, 5.98; 95% CI, 1.33-26.8; P = 0.01) independently predicted positive events in patients with ARVC. CONCLUSIONS: MTWA assessment with MMA analysis complemented by an EPS might provide improved prognostic ability in patients with ARVC with preserved LV function during long-term follow-up.


Asunto(s)
Arritmias Cardíacas/diagnóstico , Displasia Ventricular Derecha Arritmogénica/diagnóstico , Electrocardiografía/métodos , Electrofisiología/métodos , Taquicardia Ventricular/diagnóstico , Adulto , Prueba de Esfuerzo , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Función Ventricular Izquierda/fisiología
10.
Chinese Medical Journal ; (24): 1406-1413, 2019.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-799955

RESUMEN

Background@#The long-term predicted value of microvolt T-wave alternans (MTWA) for ventricular tachyarrhythmia in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) remains unclear. Our study explored the characteristics of MTWA and its prognostic value when combined with an electrophysiologic study (EPS) in patients with ARVC.@*Methods@#All patients underwent non-invasive MTWA examination with modified moving average (MMA) analysis and an EPS. A positive event was defined as the first occurrence of sudden cardiac death, documented sustained ventricular tachycardia (VT), ventricular fibrillation, or the administration of appropriate implantable cardioverter defibrillator therapy including shock or antitachycardia pacing.@*Results@#Thirty-five patients with ARVC (age 38.6 ± 11.0 years; 28 males) with preserved left ventricular (LV) function were recruited. The maximal TWA value (MaxValt) was 17.0 (11.0–27.0) μV. Sustained VT was induced in 22 patients by the EPS. During a median follow-up of 99.9 ± 7.7 months, 15 patients had positive clinical events. When inducible VT was combined with the MaxValt, the area under the curve improved from 0.739 to 0.797. The receiver operating characteristic curve showed that a MaxValt of 23.5 μV was the optimal cutoff value to identify positive events. The multivariate Cox regression model for survival showed that MTWA (MaxValt, hazard ratio [HR], 1.06; 95% confidence interval [CI], 1.01–1.11; P = 0.01) and inducible VT (HR, 5.98; 95% CI, 1.33–26.8; P = 0.01) independently predicted positive events in patients with ARVC.@*Conclusions@#MTWA assessment with MMA analysis complemented by an EPS might provide improved prognostic ability in patients with ARVC with preserved LV function during long-term follow-up.

11.
Chinese Medical Journal ; (24): 1406-1413, 2019.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-771218

RESUMEN

BACKGROUND@#The long-term predicted value of microvolt T-wave alternans (MTWA) for ventricular tachyarrhythmia in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) remains unclear. Our study explored the characteristics of MTWA and its prognostic value when combined with an electrophysiologic study (EPS) in patients with ARVC.@*METHODS@#All patients underwent non-invasive MTWA examination with modified moving average (MMA) analysis and an EPS. A positive event was defined as the first occurrence of sudden cardiac death, documented sustained ventricular tachycardia (VT), ventricular fibrillation, or the administration of appropriate implantable cardioverter defibrillator therapy including shock or anti-tachycardia pacing.@*RESULTS@#Thirty-five patients with ARVC (age 38.6 ± 11.0 years; 28 males) with preserved left ventricular (LV) function were recruited. The maximal TWA value (MaxValt) was 17.0 (11.0-27.0) μV. Sustained VT was induced in 22 patients by the EPS. During a median follow-up of 99.9 ± 7.7 months, 15 patients had positive clinical events. When inducible VT was combined with the MaxValt, the area under the curve improved from 0.739 to 0.797. The receiver operating characteristic curve showed that a MaxValt of 23.5 μV was the optimal cutoff value to identify positive events. The multivariate Cox regression model for survival showed that MTWA (MaxValt, hazard ratio [HR], 1.06; 95% confidence interval [CI], 1.01-1.11; P = 0.01) and inducible VT (HR, 5.98; 95% CI, 1.33-26.8; P = 0.01) independently predicted positive events in patients with ARVC.@*CONCLUSIONS@#MTWA assessment with MMA analysis complemented by an EPS might provide improved prognostic ability in patients with ARVC with preserved LV function during long-term follow-up.


Asunto(s)
Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Arritmias Cardíacas , Diagnóstico , Displasia Ventricular Derecha Arritmogénica , Diagnóstico , Electrocardiografía , Métodos , Electrofisiología , Métodos , Prueba de Esfuerzo , Estudios de Seguimiento , Taquicardia Ventricular , Diagnóstico , Función Ventricular Izquierda , Fisiología
12.
Pestic Biochem Physiol ; 128: 16-21, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26969435

RESUMEN

Yeast-like symbiotes (YLS) are endosymbionts that are closely related to the growth, development and reproduction of their host, the brown planthopper (BPH), Nilaparvata lugens Stål (Hemiptera: Delphacidae). In order to understand the relationship between the population of YLS in BPH cells and the survival rate of BPH, eight different fungicides were applied to rice plants infested by BPH, and the number of YLS and mortality of BPH were determined. Three of the fungicides, 27% toyocamycin & tetramycin P & tetrin B & tetramycin A, 0.01% trichodermin, and 75% trifloxystrobin & tebuconazole WG, were found to significantly reduce the number of YLS in BPH, subsequently causing a high mortality of BPH. The three fungicides were each mixed with a commonly used insecticide-imidacloprid, and the fungicide/insecticide mixtures could cause a marked reduction in YLS number in BPH, resulting in a significantly higher mortality of BPH than did the imidacloprid alone. The mixture of 27% toyocamycin & tetramycin P & tetrin B & tetramycin A with imidacloprid showed the best inhibitory effect on BPH population. Our study demonstrated a high dependence of the BPH survival rate on the number of YLS harbored in BPH fat-body cells. It implies that using specific fungicides as an additive to imidacloprid for controlling BPH could be a novel way to enhance the efficacy of insecticide, minimizing the use of imidacloprid in paddy fields.


Asunto(s)
Fungicidas Industriales/farmacología , Hemípteros/efectos de los fármacos , Simbiosis , Animales , Hemípteros/microbiología
13.
Proc Natl Acad Sci U S A ; 113(7): 1913-8, 2016 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-26839410

RESUMEN

Visual processing depends critically on the receptive field (RF) properties of visual neurons. However, comprehensive characterization of RFs beyond the primary visual cortex (V1) remains a challenge. Here we report fine RF structures in secondary visual cortex (V2) of awake macaque monkeys, identified through a projection pursuit regression analysis of neuronal responses to natural images. We found that V2 RFs could be broadly classified as V1-like (typical Gabor-shaped subunits), ultralong (subunits with high aspect ratios), or complex-shaped (subunits with multiple oriented components). Furthermore, single-unit recordings from functional domains identified by intrinsic optical imaging showed that neurons with ultralong RFs were primarily localized within pale stripes, whereas neurons with complex-shaped RFs were more concentrated in thin stripes. Thus, by combining single-unit recording with optical imaging and a computational approach, we identified RF subunits underlying spatial feature selectivity of V2 neurons and demonstrated the functional organization of these RF properties.


Asunto(s)
Macaca/fisiología , Neuronas/fisiología , Corteza Visual/fisiología , Vigilia , Animales , Modelos Biológicos , Corteza Visual/citología
14.
Sci Rep ; 5: 14125, 2015 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-26370138

RESUMEN

Extracellular transients of pH alterations likely mediate signal transduction in the nervous system. Neuronal acid-sensing ion channels (ASICs) act as sensors for extracellular protons, but the mechanism underlying ASIC activation remains largely unknown. Here, we show that, following activation of a light-activated proton pump, Archaerhodopsin-3 (Arch), proton transients induced ASIC currents in both neurons and HEK293T cells co-expressing ASIC1a channels. Using chimera proteins that bridge Arch and ASIC1a by a glycine/serine linker, we found that successful coupling occurred within 15 nm distance. Furthermore, two-cell sniffer patch recording revealed that regulated release of protons through either Arch or voltage-gated proton channel Hv1 activated neighbouring cells expressing ASIC1a channels. Finally, computational modelling predicted the peak proton concentration at the intercellular interface to be at pH 6.7, which is acidic enough to activate ASICs in vivo. Our results highlight the pathophysiological role of proton signalling in the nervous system.


Asunto(s)
Canales Iónicos Sensibles al Ácido/metabolismo , Protones , Transducción de Señal , Animales , Línea Celular , Fenómenos Electrofisiológicos/efectos de la radiación , Humanos , Luz , Ratones
15.
J Neurosci ; 35(22): 8384-93, 2015 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-26041908

RESUMEN

Dendrite development of newborn granule cells (GCs) in the dentate gyrus of adult hippocampus is critical for their incorporation into existing hippocampal circuits, but the cellular mechanisms regulating their dendrite development remains largely unclear. In this study, we examined the function of brain-derived neurotrophic factor (BDNF), which is expressed in adult-born GCs, in regulating their dendrite morphogenesis. Using retrovirus-mediated gene transfection, we found that deletion and overexpression of BDNF in adult-born GCs resulted in the reduction and elevation of dendrite growth, respectively. This effect was mainly due to the autocrine rather than paracrine action of BDNF, because deletion of BDNF only in the newborn GCs resulted in dendrite abnormality of these neurons to a similar extent as that observed in conditional knockout (cKO) mice with BDNF deleted in the entire forebrain. Furthermore, selective expression of BDNF in adult-born GCs in BDNF cKO mice fully restored normal dendrite development. The BDNF autocrine action was also required for the development of normal density of spines and normal percentage of spines containing the postsynaptic marker PSD-95, suggesting autocrine BDNF regulation of synaptogenesis. Furthermore, increased dendrite growth of adult-born GCs caused by voluntary exercise was abolished by BDNF deletion specifically in these neurons and elevated dendrite growth due to BDNF overexpression in these neurons was prevented by reducing neuronal activity with coexpression of inward rectifier potassium channels, consistent with activity-dependent autocrine BDNF secretion. Therefore, BDNF expressed in adult-born GCs plays a critical role in dendrite development by acting as an autocrine factor.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/metabolismo , Dendritas/fisiología , Hipocampo/citología , Neuronas/citología , Actinas/metabolismo , Análisis de Varianza , Animales , Animales Recién Nacidos , Factor Neurotrófico Derivado del Encéfalo/genética , Homólogo 4 de la Proteína Discs Large , Proteínas de Dominio Doblecortina , Guanilato-Quinasas/metabolismo , Proteínas Luminiscentes/genética , Proteínas Luminiscentes/metabolismo , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Proteínas Asociadas a Microtúbulos/metabolismo , Nestina/genética , Nestina/metabolismo , Neuropéptidos/metabolismo , Transfección
16.
Proc Natl Acad Sci U S A ; 111(1): 469-74, 2014 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-24367100

RESUMEN

Adult-born granule cells in the dentate gyrus of the rodent hippocampus are important for memory formation and mood regulation, but the cellular mechanism underlying their polarized development, a process critical for their incorporation into functional circuits, remains unknown. We found that deletion of the serine-threonine protein kinase LKB1 or overexpression of dominant-negative LKB1 reduced the polarized initiation of the primary dendrite from the soma and disrupted its oriented growth toward the molecular layer. This abnormality correlated with the dispersion of Golgi apparatus that normally accumulated at the base and within the initial segment of the primary dendrite, and was mimicked by disrupting Golgi organization via altering the expression of Golgi structural proteins GM130 or GRASP65. Thus, besides its known function in axon formation in embryonic pyramidal neurons, LKB1 plays an additional role in regulating polarized dendrite morphogenesis in adult-born granule cells in the hippocampus.


Asunto(s)
Dendritas/metabolismo , Giro Dentado/metabolismo , Hipocampo/metabolismo , Neurogénesis , Neuronas/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Quinasas Activadas por AMP , Animales , Animales Recién Nacidos , Autoantígenos/metabolismo , Axones/metabolismo , Proteínas Portadoras/metabolismo , Polaridad Celular , Proliferación Celular , Regulación de la Expresión Génica , Aparato de Golgi/metabolismo , Proteínas Fluorescentes Verdes/metabolismo , Hipocampo/citología , Péptidos y Proteínas de Señalización Intracelular , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Microscopía Confocal , Fosforilación
17.
Clin Respir J ; 8(1): 100-7, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23906186

RESUMEN

INTRODUCTION: Fibreoptic intubation is a valuable technique for difficult airway management in which conscious sedation is paramount. OBJECTIVES: To investigate the efficacy and safety of dexmedetomidine (DEX) and sufentanil (SUF) for conscious sedation during awake nasotracheal intubation under vision by a fibreoptic bronchoscope. METHODS: Forty patients with anticipated difficult airways of American Society of Anesthesiologists I-II scheduled for awake fibreoptic nasotracheal intubation were randomised into two groups each containing 20 subjects. DEX group received DEX at a dose of 1.0 µg/kg over 10 min followed by a continuous infusion of 0.5 µg/kg per hour, while SUF group received SUF target controlled infusion in which the target plasma concentration was 0.3 ng/mL. The nasotracheal intubation conditions and the tolerance to nasotracheal intubation were observed; the occurrence of adverse events including hypertension, bradycardia and respiratory depression during nasotracheal intubation and post-surgical throat pain and hoarseness, and post-surgical memory score were recorded. RESULTS: Better nasotracheal intubation conditions and higher tolerance to intubation were observed in DEX group than those in SUF group (P < 0.05). The incidence rates of hypertension, respiratory depression during intubation and throat pain after surgery were lower in DEX group than those in SUF group; however, the incidence of bradycardia was higher in DEX group than that in SUF group. CONCLUSIONS: DEX provides better nasotracheal intubation conditions, improves patients' tolerance to intubation and leads to lower occurrence of hypertension, respiratory depression and throat pain and post-surgical memory score for sedation during awake fibreoptic nasotracheal intubation.


Asunto(s)
Sedación Consciente , Dexmedetomidina/administración & dosificación , Hipnóticos y Sedantes/administración & dosificación , Intubación Intratraqueal/métodos , Sufentanilo/administración & dosificación , Adulto , Anciano , Sedación Consciente/métodos , Femenino , Tecnología de Fibra Óptica , Mortalidad Hospitalaria , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Estudios Prospectivos , Adulto Joven
18.
Neuropharmacology ; 77: 90-9, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24055498

RESUMEN

Aberrant CDK5 activity is implicated in a number of neurodegenerative disorders. Isoflurane exposure leads to neuronal apoptosis, and subsequent learning and memory defects in the developing brain. The present study was designed to examine whether and how CDK5 activity plays a role in developmental isoflurane neurotoxicity. Rat pups and hippocampal neuronal cultures were exposed to 1.5% isoflurane for 4 h. The protein and mRNA levels of CDK5, p35 and p25 were detected by western blot and QReal-Time PCR. CDK5 activity was evaluated in vitro using Histone H1 as a substrate. Roscovitine (an inhibitor of CDK5) was applied before isoflurane treatment, cleaved Caspase-3, Bcl-2, Bax, MEF2 and phospho-MEF2A-Ser-408 expressions were determined. Dominant-Negative CDK5 was transfected before isoflurane treatment. Neuronal apoptosis was evaluated by Flow cytometry (FCM) and TUNEL-staining. Cognitive functions were assessed by Morris water maze. We found that isoflurane treatment led to an aberrant CDK5 activation due to its activator p25 that was cleaved from p35 by calpain. Inhibition of CDK5 activity with Roscovitine enhanced Bcl-2, and decreased cleaved Caspase-3 and Bax expressions. In addition, isoflurane exposure resulted in a decrease of MEF2 and increase of phospho-MEF2A-Ser-408, which were rescued by Roscovitine or Dominant-Negative CDK5 transfection. Dominant-Negative CDK5 transfection also decreased the percentage of TUNEL-positive cells in isoflurane neurotoxicity. Moreover, Roscovitine remarkably alleviated the learning and memory deficits induced by postnatal isoflurane exposure. These results indicated that aberrant CDK5 activity-dependent MEF2 phosphorylation mediates developmental isoflurane neurotoxicity. Inhibition of CDK5 overactivation contributes to the relief of isoflurane neurotoxicity in the developing brain.


Asunto(s)
Quinasa 5 Dependiente de la Ciclina/antagonistas & inhibidores , Hipocampo/efectos de los fármacos , Isoflurano/toxicidad , Neuronas/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Purinas/farmacología , Animales , Células Cultivadas , Quinasa 5 Dependiente de la Ciclina/metabolismo , Hipocampo/citología , Hipocampo/metabolismo , Aprendizaje por Laberinto/efectos de los fármacos , Enfermedades Neurodegenerativas/metabolismo , Neuronas/citología , Neuronas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Ratas Sprague-Dawley , Roscovitina
19.
Ann Pharmacother ; 47(11): 1391-9, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24259599

RESUMEN

BACKGROUND: It has been reported that dexmedetomidine (DEX) can be used for conscious sedation in awake craniotomy, but few data exist to compare DEX versus propofol (PRO). OBJECTIVE: To compare the efficacy and safety of DEX versus PRO for conscious sedation in awake craniotomy. METHODS: Thirty patients of American Society of Anesthesiologists grade I-II scheduled for awake craniotomy, were randomized into 2 groups each containing 15 subjects. Group D received DEX and group P received PRO. Two minutes after tracheal intubation (T1), PRO (target plasma concentration) was titrated down to 1 to 4 µg/mL in group P. In group D, PRO was discontinued and DEX was administered 1.0 µg/kg followed by a maintenance dose of 0.2 to 0.7 µg/kg/h. The surgeon preset the anticipated awake point-in-time (T0) preoperatively. Ten minutes before T0 (T3), DEX was titrated down to 0.2 µg/kg/h in group D, PRO was discontinued and normal saline (placebo) 5 mL/h was infused in group P. Arousal time, quality of revival and adverse events during the awake period, degree of satisfaction from surgeons and patients were recorded. RESULTS: Arousal time was significantly shorter in group D than in group P (P < .001). The quality of revival during the awake period in group D was similar to that of group P (P = .68). The degree of satisfaction of surgeons was significantly higher in group D than in group P (P < .001), but no difference was found between the 2 groups with respect to patient satisfaction (P = .80). There was no difference between the 2 groups in the incidence of adverse events during the awake period (P > .05). CONCLUSIONS: Either DEX or PRO can be effectively and safely used for conscious sedation in awake craniotomy. Comparing the two, DEX produced a shorter arousal time and a higher degree of surgeon satisfaction.


Asunto(s)
Periodo de Recuperación de la Anestesia , Sedación Consciente/métodos , Craneotomía/métodos , Dexmedetomidina/uso terapéutico , Hipnóticos y Sedantes/uso terapéutico , Propofol/uso terapéutico , Dexmedetomidina/administración & dosificación , Dexmedetomidina/efectos adversos , Dexmedetomidina/sangre , Método Doble Ciego , Femenino , Humanos , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/efectos adversos , Hipnóticos y Sedantes/sangre , Intubación Intratraqueal , Masculino , Persona de Mediana Edad , Propofol/administración & dosificación , Propofol/efectos adversos , Propofol/sangre , Estudios Prospectivos
20.
Proc Natl Acad Sci U S A ; 110(29): E2714-23, 2013 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-23812756

RESUMEN

How developing axons in the corpus callosum (CC) achieve their homotopic projection to the contralateral cortex remains unclear. We found that axonal position within the CC plays a critical role in this projection. Labeling of nearby callosal axons in mice showed that callosal axons were segregated in an orderly fashion, with those from more medial cerebral cortex located more dorsally and subsequently projecting to more medial contralateral cortical regions. The normal axonal order within the CC was grossly disturbed when semaphorin3A/neuropilin-1 signaling was disrupted. However, the order in which axons were positioned within the CC still determined their contralateral projection, causing a severe disruption of the homotopic contralateral projection that persisted at postnatal day 30, when the normal developmental refinement of contralateral projections is completed in wild-type (WT) mice. Thus, the orderly positioning of axons within the CC is a primary determinant of how homotopic interhemispheric projections form in the contralateral cortex.


Asunto(s)
Axones/fisiología , Cuerpo Calloso/embriología , Vías Nerviosas/embriología , Neuropilina-1/metabolismo , Semaforina-3A/metabolismo , Transducción de Señal/fisiología , Animales , Bisbenzimidazol , Cuerpo Calloso/citología , Electroporación , Hibridación in Situ , Ratones , Ratones Endogámicos C57BL , Microscopía Fluorescente
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