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The human brain continuously generates predictions of incoming sensory input and calculates corresponding prediction errors from the perceived inputs to update internal predictions. In human primary somatosensory cortex (area 3b), different cortical layers are involved in receiving the sensory input and generation of error signals. It remains unknown, however, how the layers in the human area 3b contribute to the temporal prediction error processing. To investigate prediction error representation in the area 3b across layers, we acquired layer-specific functional magnetic resonance imaging (fMRI) data at 7T from human area 3b during a task of index finger poking with no-delay, short-delay and long-delay touching sequences. We demonstrate that all three tasks increased activity in both superficial and deep layers of area 3b compared to the random sensory input. The fMRI signal was differentially modulated solely in the deep layers rather than the superficial layers of area 3b by the delay time. Compared with the no-delay stimuli, activity was greater in the deep layers of area 3b during the short-delay stimuli but lower during the long-delay stimuli. This difference activity features in the superficial and deep layers suggest distinct functional contributions of area 3b layers to tactile temporal prediction error processing. The functional segregation in area 3b across layers may reflect that the excitatory and inhibitory interplay in the sensory cortex contributions to flexible communication between cortical layers or between cortical areas.
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Mapeo Encefálico , Dedos/fisiología , Imagen por Resonancia Magnética/métodos , Corteza Somatosensorial/fisiología , Percepción del Tiempo , Tacto/fisiología , Adulto , Femenino , Voluntarios Sanos , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
PURPOSE: We investigate the influence of moving blood-attenuation effects when using "delay alternating with nutation for tailored excitation" (DANTE) pulses in conjunction with blood oxygen level dependent (BOLD) of functional MRI (fMRI) at 3 T. Based on the effects of including DANTE pulses, we propose quantification of cerebral blood volume (CBV) changes following functional stimulation. METHODS: Eighteen volunteers in total underwent fMRI scans at 3 T. Seven volunteers were scanned to investigate the effects of DANTE pulses on the fMRI signal. CBV changes in response to visual stimulation were quantified in 11 volunteers using a DANTE-prepared dual-echo EPI sequence. RESULTS: The inflow effects from flowing blood in arteries and draining vein effects from flowing blood in large veins can be suppressed by use of a DANTE preparation module. Using DANTE-prepared dual-echo EPI, we quantitatively measured intravascular-weighted microvascular CBV changes of 25.4%, 29.8%, and 32.6% evoked by 1, 5, and 10 Hz visual stimulation, respectively. The extravascular fraction (∆S/S)extra at TE = 30 ms in total BOLD signal was determined to be 64.8 ± 3.4%, which is in line with previous extravascular component estimation at 3 T. Results show that the microvascular CBV changes are linearly dependent on total BOLD changes at TE = 30 ms with a slope of 0.113, and this relation is independent of stimulation frequency and subject. CONCLUSION: The DANTE preparation pulses can be incorporated into a standard EPI fMRI sequence for the purpose of minimizing inflow effects and reducing draining veins effects in large vessels. Additionally, the DANTE-prepared dual-echo EPI sequence is a promising fast imaging tool for quantification of intravascular-weighted CBV change in the microvascular space at 3 T.
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Volumen Sanguíneo Cerebral , Imagen por Resonancia Magnética , Encéfalo/diagnóstico por imagen , Circulación Cerebrovascular/fisiología , Humanos , Imagen por Resonancia Magnética/métodos , Estimulación LuminosaRESUMEN
The increased availability of ultra-high field scanners provides an opportunity to perform fMRI at sub-millimeter spatial scales and enables in vivo probing of laminar function in the human brain. In most previous studies, the definition of cortical layers, or depths, is based on an anatomical reference image that is collected by a different acquisition sequence and exhibits different geometric distortion compared to the functional images. Here, we propose to generate the anatomical image with the fMRI acquisition technique by incorporating magnetization transfer (MT) weighted imaging. Small flip angle binomial pulse trains are used as MT preparation, with a flexible duration (several to tens of milliseconds), which can be applied before each EPI segment without constraining the acquisition length (segment or slice number). The method's feasibility was demonstrated at 7T for coverage of either a small slab or the near-whole brain at 0.8 mm isotropic resolution. Tissue contrast was found to be similar to that obtained with a state-of-art anatomical reference based on MP2RAGE. This MT-weighted EPI image allows an automatic reconstruction of the cortical surface to support laminar analysis in native fMRI space, obviating the need for distortion correction and registration.
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Corteza Cerebral/diagnóstico por imagen , Imagen Eco-Planar/métodos , Mapeo Encefálico/métodos , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodosRESUMEN
Earlier research in cats has shown that both cerebral blood volume (CBV) and cerebral blood flow (CBF) can be used to identify layer-dependent fMRI activation with spatial specificity superior to gradient-echo blood-oxygen-level-dependent (BOLD) contrast (Jin and Kim, 2008a). CBF contrast of perfusion fMRI at ultra-high field has not been widely applied in humans to measure laminar activity due to its low sensitivity, while CBV contrast for fMRI using vascular space occupancy (VASO) has been successfully used. However, VASO can be compromised by interference of blood in-flow effects and a temporally limited acquisition window around the blood-nulling time point. Here, we proposed to use DANTE (Delay Alternating with Nutation for Tailored Excitation) pulse trains combined with 3D-EPI to acquire an integrated VASO and perfusion (VAPER) contrast. The signal origin of the VAPER contrast was theoretically evaluated with respect to its CBV and CBF contributions using a four-compartment simulation model. The feasibility of VAPER to measure layer-dependent activity was empirically investigated in human primary motor cortex at 7 âT. We demonstrated this new tool, with its highly specified functional layer profile, robust reproducibility, and improved sensitivity, to allow investigation of layer-specific cortical functions.
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Encéfalo/fisiología , Volumen Sanguíneo Cerebral/fisiología , Circulación Cerebrovascular/fisiología , Oxígeno/sangre , Algoritmos , Animales , Volumen Sanguíneo/fisiología , Mapeo Encefálico/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Reproducibilidad de los ResultadosRESUMEN
Studies of visual temporal frequency preference typically examine frequencies under 20â¯Hz and measure local activity to evaluate the sensitivity of different cortical areas to variations in temporal frequencies. Most of these studies have not attempted to map preferred temporal frequency within and across visual areas, nor have they explored in detail, stimuli at gamma frequency, which recent research suggests may have potential clinical utility. In this study, we address this gap by using functional magnetic resonance imaging (fMRI) to measure response to flickering visual stimuli varying in frequency from 1 to 40â¯Hz. We apply stimulation in both a block design to examine task response and a steady-state design to examine functional connectivity. We observed distinct activation patterns between 1â¯Hz and 40â¯Hz stimuli. We also found that the correlation between medial thalamus and visual cortex was modulated by the temporal frequency. The modulation functions and tuned frequencies are different for the visual activity and thalamo-visual correlations. Using both fMRI activity and connectivity measurements, we show evidence for a temporal frequency specific organization across the human visual system.
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Tálamo/fisiología , Corteza Visual/fisiología , Percepción Visual/fisiología , Adolescente , Adulto , Mapeo Encefálico , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estimulación Luminosa , Factores de Tiempo , Vías Visuales/fisiología , Adulto JovenRESUMEN
Transcranial alternating current stimulation (tACS) has emerged as a promising tool for modulating cortical oscillations. In previous electroencephalogram (EEG) studies, tACS has been found to modulate brain oscillatory activity in a frequency-specific manner. However, the spatial distribution and hemodynamic response for this modulation remains poorly understood. Functional magnetic resonance imaging (fMRI) has the advantage of measuring neuronal activity in regions not only below the tACS electrodes but also across the whole brain with high spatial resolution. Here, we measured fMRI signal while applying tACS to modulate rhythmic visual activity. During fMRI acquisition, tACS at different frequencies (4, 8, 16, and 32 Hz) was applied along with visual flicker stimulation at 8 and 16 Hz. We analyzed the blood-oxygen-level-dependent (BOLD) signal difference between tACS-ON vs tACS-OFF, and different frequency combinations (e.g., 4 Hz tACS, 8 Hz flicker vs 8 Hz tACS, 8 Hz flicker). We observed significant tACS modulation effects on BOLD responses when the tACS frequency matched the visual flicker frequency or the second harmonic frequency. The main effects were predominantly seen in regions that were activated by the visual task and targeted by the tACS current distribution. These findings bridge different scientific domains of tACS research and demonstrate that fMRI could localize the tACS effect on stimulus-induced brain rhythms, which could lead to a new approach for understanding the high-level cognitive process shaped by the ongoing oscillatory signal.
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Encéfalo/irrigación sanguínea , Encéfalo/fisiología , Oxígeno/sangre , Psicofísica , Estimulación Transcraneal de Corriente Directa/métodos , Percepción Visual/fisiología , Adulto , Mapeo Encefálico , Femenino , Voluntarios Sanos , Humanos , Imagen por Resonancia Magnética , Masculino , Estimulación Luminosa , Factores de Tiempo , Adulto JovenRESUMEN
The direct detection of neuronal electrical activity is one of the most challenging goals in non-BOLD fMRI research. Previous work has demonstrated its feasibility in phantom and cell culture studies, but attempts in in vivo studies remain few and far between. Most recent in vivo studies used T2*-weighted sequences to directly detect neuronal electrical activity evoked by sensory stimulus. As neuronal electrical signal is usually comprised of a series of spectrally distributed oscillatory waveforms rather than being a direct current, it is most likely to be detected using oscillatory current sensitive sequences. In this study, we explored the potential of using the spin-lock oscillatory excitation (SLOE) sequence with spiral readout to directly detect optogenetically evoked oscillatory neuronal electrical activity, whose main spectral component can be manipulated artificially to match the resonance frequency of spin-lock RF field. In addition, experiments using the stimulus-induced rotary saturation (SIRS) sequence with spiral readout were also performed. Electrophysiological recording and MRI data acquisition were conducted on separate animals. Robust optogenetically evoked oscillatory LFP signals were observed and significant BOLD signals were acquired with the GE-EPI sequence before and after the whole SLOE and SIRS acquisitions, but no significant neuronal current MRI (ncMRI) signal changes were detected. These results indicate that the sensitivity of oscillatory current sensitive sequences needs to be further improved for direct detection of neuronal electrical activity.
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Mapeo Encefálico/métodos , Encéfalo/fisiología , Neuronas/fisiología , Optogenética , Animales , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Fantasmas de Imagen , Ratas , Ratas Sprague-DawleyRESUMEN
PURPOSE: Direct mapping of neuronal currents using MRI would have fundamental impacts on brain functional imaging. Previous reports indicated that the stimulus-induced rotary saturation (SIRS) mechanism had the best potential of direct detection of neural oscillations; however, it lacked the high-sensitivity level needed. In this study, a novel strategy is proposed in an effort to improve the detection sensitivity. METHODS: In our modified SIRS sequence, an external oscillatory magnetic field is used as the excitation pulse in place of the standard 90-degree excitation pulse. This approach could potentially lead to tens or even hundreds times of enhancement in the detection sensitivity for low field signals. It also helps to lower the physiological noise, allows for shorter pulse repetition time, and is less affected by the blood oxygen level. RESULTS: We demonstrate that a 100-Hz oscillatory magnetic field with magnitude as low as 0.25 nanotesla generated in a current loop can be robustly detected using a 3-Tesla MRI scanner. CONCLUSION: The modified SIRS sequence offers higher detection sensitivity as well as several additional advantages. These promising results suggest that the direct detection of neural oscillation might be within the grasp of the current MRI technology.
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Campos Magnéticos , Imagen por Resonancia Magnética/métodos , Humanos , Aumento de la Imagen/métodos , Neuronas/fisiología , Fantasmas de Imagen , Sensibilidad y EspecificidadRESUMEN
Cyclosporine A (CsA) is the prevalent immunosuppressive drug for preventing and treating graft-versus-host disease after hematopoietic stem cell transplantation (HSCT) in both children and adults. Population pharmacokinetic studies have identified covariates, owing to their large between-subject variability, facilitating individualized therapy. However, no review has summarized CsA's population pharmacokinetics post-HSCT. This systematic review aims to synthesize population pharmacokinetic studies of CsA therapy in HSCT recipients and explore influencing covariates. Thirteen studies, comprising five involving children, one involving both children and adults and seven involving adults, were included. The median apparent clearance in children surpassed that in adults, influenced notably by hematocrit level and body. While liver function impacted clearance, the effect was insignificant. Co-administration with cytochrome P450 enzyme inhibitors (e.g., fluconazole or itraconazole) decreased drug clearance, whereas inducers (e.g., rifampicin or rifapentine) increased it. Area under the curve analysis is recommended over trough concentration-based monitoring for HSCT recipients on CsA. In cases of insufficient trough concentration, additional sampling points are recommended for improved area under the curve estimation. Further studies are needed to evaluate the optimal sampling points required for the area under the curve estimation in CsA therapy post-HSCT.
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BACKGROUND: Tacrolimus is a critical component of immunosuppressive therapy for kidney transplant recipients. Intra-patient variation (IPV) of tacrolimus levels affects the function of transplanted kidney. AIM: This study aimed to investigate the impact of tacrolimus IPV on kidney function, examine its association with post-transplant duration, and assess its effect on the immune status of transplant recipients. METHOD: This retrospective study was conducted from January 2016 to February 2022. IPV was evaluated using the coefficient of variation (CV) of tacrolimus trough levels from 6 to 48 months after transplantation. Patients were divided into low- and high-IPV groups based on the median CV. Significant differences in kidney function, CD4 + /CD8 + ratio, and post-transplant duration between these groups were analyzed. RESULTS: Among 189 patients, tacrolimus IPV showed a strong correlation with serum creatinine clearance rate (Ccr) and estimated glomerular filtration rate (eGFR) (p < 0.05). Tacrolimus IPV was significantly correlated with post-transplant duration in only two patients (p < 0.05). Using a median CV of 15.4% to categorize patients, the high IPV group, compared to the low IPV group, exhibited significantly higher eGFR at 6-9 months (p < 0.05), lower Ccr at 9-12 months (p < 0.05), and reduced Ccr and eGFR at 15-18 months (p < 0.05). Six months after transplantation, the high IPV group had a significantly lower CD4 + /CD8 + ratio than the low IPV group (p < 0.05). CONCLUSION: This study highlights the significant impact of tacrolimus IPV on transplant kidney function and immune status in transplant patients at various post-transplantation intervals.
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Inmunosupresores , Trasplante de Riñón , Tacrolimus , Humanos , Tacrolimus/administración & dosificación , Tacrolimus/uso terapéutico , Tacrolimus/farmacocinética , Estudios Retrospectivos , Masculino , Femenino , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéutico , Persona de Mediana Edad , Adulto , Relación CD4-CD8 , Tasa de Filtración Glomerular/efectos de los fármacos , Aloinjertos/efectos de los fármacos , AncianoRESUMEN
Depression is a common and serious mental disorder. Data on its pathogenesis remain unclear and the options of drug treatments are limited. Here, we explored the role of pyroptosis, a novel pro-inflammatory programmed cell death process, in depression as well as the anti-depression effects and mechanisms of salidroside (Sal), a bioactive extract from Rhodiola rosea L. We established a corticosterone (CORT)-induced or lipopolysaccharide (LPS)-induced mice in vivo, and CORT, or nigericin (NLRP3 agonist)-induced PC12 cells in vitro. Our findings demonstrated that Sal profoundly mediated CORT or LPS-induced depressive behavior and improved synaptic plasticity by upregulating the expression of brain-derived neurotrophic factor (BDNF) gene. The data showed upregulation of proteins associated with NLRP3-mediated pyroptosis, including NLRP3, cleaved Caspase-1, IL-1ß, IL-18, and cleaved GSDMD. The molecular docking simulation predicted that Sal would interact with P2X7 of the P2X7/NF-κB/NLRP3 signaling pathway. In addition, our findings showed that the NLRP3-mediated pyroptosis was regulated by P2X7/NF-κB/NLRP3 signaling pathway. Interestingly, Sal was shown to ameliorate depression via suppression of the P2X7/NF-κB/NLRP3 mediated pyroptosis, and rescued nigericin-induced pyroptosis in the PC12 cells. Besides, knock down of the NLRP3 gene by siRNA markedly increased the inhibitory effects of Sal on pyroptosis and proinflammatory responses. Taken together, our findings demonstrated that pyroptosis plays a crucial role in depression, and Sal ameliorates depression by suppressing the P2X7/NF-κB/NLRP3-mediated pyroptosis. Thus, our study provides new insights into the potential treatment options for depression.
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Viewing faces that are perceived as emotionally expressive evokes enhanced neural responses in multiple brain regions, a phenomenon thought to depend critically on the amygdala. This emotion-related modulation is evident even in primary visual cortex (V1), providing a potential neural substrate by which emotionally salient stimuli can affect perception. How does emotional valence information, computed in the amygdala, reach V1? Here we use high-resolution functional MRI to investigate the layer profile and retinotopic distribution of neural activity specific to emotional facial expressions. Across three experiments, human participants viewed centrally presented face stimuli varying in emotional expression and performed a gender judgment task. We found that facial valence sensitivity was evident only in superficial cortical layers and was not restricted to the retinotopic location of the stimuli, consistent with diffuse feedback-like projections from the amygdala. Together, our results provide a feedback mechanism by which the amygdala directly modulates activity at the earliest stage of visual processing.
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Expresión Facial , Corteza Visual , Humanos , Corteza Visual/fisiología , Emociones/fisiología , Amígdala del Cerebelo/fisiología , Percepción Visual/fisiología , Mapeo Encefálico , Imagen por Resonancia MagnéticaRESUMEN
Amyloid ß-protein (Aß) is reported to activate NLRP3 inflammasomes and drive pyroptosis, which is subsequently involved in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD). To date, the pathogenesis of AD is unfortunately insufficiently elucidated. Therefore, this study was conducted to explore whether Salidroside (Sal) treatment could benefit AD by improving pyroptosis. Firstly, two animal models of AD, induced, respectively, by Aß1-42 and D-galactose (D-gal)/AlCl3, have been created to assist our appreciation of AD pathophysiology. We then confirmed that pyroptosis is related to the pathogenesis of AD, and Sal can slow the progression of AD by inhibiting pyroptosis. Subsequently, we established the D-gal and Nigericin-induced PC12 cells injury model in vitro to verify Sal blocks pyroptosis mainly by targeting the NLRP3 inflammasome. For in vivo studies, we observed that Aß accumulation, Tau hyperphosphorylation, neurons of hippocampal damage, and cognitive dysfunction in AD mice, caused by bilateral injection of Aß1-42 into the hippocampus and treatments with D-gal combine AlCl3. Besides, accumulated Aß promotes NLRP3 inflammasome activation, which leads to the activation and release of a pro-inflammatory cytokine, interleukin-1 beta (IL-1ß). Notably, both Aß accumulation and hyperphosphorylation of Tau decreased and inhibited pyroptosis by downregulating the expression of IL-1ß and IL-18, which can be attributed to the treatment of Sal. We further found that Sal can reverse the increased protein expression of TLR4, MyD88, NF-κB, P-NF-κB, NLRP3, ASC, cleaved Caspase-1, cleaved GSDMD, IL-1ß, and IL-18 in vitro. The underlying mechanism may be through inhibiting TLR4/NF-κB/NLRP3/Caspase-1 signaling pathway. Our study highlights the importance of NLRP3 inflammasome-mediated pyroptosis in AD, and how the administration of pharmacological doses of Sal can inhibit NLRP3 inflammasome-mediated pyroptosis and ameliorate AD. Thus, we conclude that NLRP3 inflammasome-mediated pyroptosis plays a significant role in AD and Sal could be a therapeutic drug for AD.
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The brain is capable of integrating signals from multiple sensory modalities. Such multisensory integration can occur in areas that are commonly considered unisensory, such as planum temporale (PT) representing the auditory association cortex. However, the roles of different afferents (feedforward vs. feedback) to PT in multisensory processing are not well understood. Our study aims to understand that by examining laminar activity patterns in different topographical subfields of human PT under unimodal and multisensory stimuli. To this end, we adopted an advanced mesoscopic (sub-millimeter) fMRI methodology at 7 T by acquiring BOLD (blood-oxygen-level-dependent contrast, which has higher sensitivity) and VAPER (integrated blood volume and perfusion contrast, which has superior laminar specificity) signal concurrently, and performed all analyses in native fMRI space benefiting from an identical acquisition between functional and anatomical images. We found a division of function between visual and auditory processing in PT and distinct feedback mechanisms in different subareas. Specifically, anterior PT was activated more by auditory inputs and received feedback modulation in superficial layers. This feedback depended on task performance and likely arose from top-down influences from higher-order multimodal areas. In contrast, posterior PT was preferentially activated by visual inputs and received visual feedback in both superficial and deep layers, which is likely projected directly from the early visual cortex. Together, these findings provide novel insights into the mechanism of multisensory interaction in human PT at the mesoscopic spatial scale.
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Mapeo Encefálico , Encéfalo , Estimulación Acústica , Percepción Auditiva , Humanos , Imagen por Resonancia MagnéticaRESUMEN
Recent methodological advances in fMRI contrast and readout strategies have allowed researchers to approach the mesoscopic spatial regime of cortical layers. This has revolutionized the ability to map cortical information processing within and across brain systems. However, until recently, most layer-fMRI studies have been confined to primary cortices using basic block-design tasks and macro-vascular-contaminated sequence contrasts. To become an established method for user-friendly applicability in neuroscience practice, layer-fMRI acquisition and analysis methods need to be extended to more flexible connectivity-based experiment designs; they must be able to capture subtle changes in brain networks of higher-order cognitive areas, and they should not be spatially biased with unwanted vein signals. In this article, we review the most pressing challenges of layer-dependent fMRI for large-scale neuroscientific applicability and describe recently developed acquisition methodologies that can resolve them. In doing so, we review technical tradeoffs and capabilities of modern MR-sequence approaches to achieve measurements that are free of locally unspecific vein signal, with whole-brain coverage, sub-second sampling, high resolutions, and with a combination of those capabilities. The presented approaches provide whole-brain layer-dependent connectivity data that open a new window to investigate brain network connections. We exemplify this by reviewing a number of candidate tools for connectivity analyses that will allow future studies to address new questions in network neuroscience. The considered network analysis tools include: hierarchy mapping, directional connectomics, source-specific connectivity mapping, and network sub-compartmentalization. We conclude: Whole-brain layer-fMRI without large-vessel contamination is applicable for human neuroscience and opens the door to investigate biological mechanisms behind any number of psychological and psychiatric phenomena, such as selective attention, hallucinations and delusions, and even conscious perception.
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Conectoma , Atención , Encéfalo/irrigación sanguínea , Encéfalo/diagnóstico por imagen , Mapeo Encefálico/métodos , Cognición , Conectoma/métodos , Humanos , Imagen por Resonancia Magnética/métodosRESUMEN
In plants, jasmonate ZIM-domain proteins (JAZs) act as critical regulators, interacting physically with transcription factors (TFs) and other transcriptional regulators to modulate jasmonate (JA)-responsive gene expression and participate in crosstalk with other hormone signalling pathways. Identifying novel JAZ-interacting proteins will provide new insights into JA signalling cascades in plants. Here, we performed yeast two-hybrid screening to identify 70 NtJAZ1-interacting proteins, including an A/T-rich interaction domain containing protein 1 (NtAIDP1) from JA-treated tobacco Bright Yellow-2 (BY-2) cells. NtAIDP1 is localised in the nucleus and interacts with NtJAZ1 via its C-terminal heat shock protein 20 (HSP) domain. Aside from NtJAZ1, NtAIDP1 also interacts with other JA-inducible NtJAZs, including NtJAZ2b, NtJAZ2b.2, NtJAZ5, NtJAZ7, NtJAZ11 and NtJAZ12, but not with NtJAZ3, NtJAZ3b or NtJAZ10, and interacts with NtNINJA, NtDELLA1 and NtDELLA2 in the yeast two-hybrid assay. Furthermore, NtAIDP1 binds to the AT-rich region of the GAG fragment of the putrescine N-methyltransferase 1a (NtPMT1a) promoter and activates the transcriptional activity of the GAG fragment, whereas NtMYC2a interacts with and competitively inhibits the transactivational activity of NtAIDP1 in Arabidopsis mesophyll protoplasts. Overexpression of NtAIDP1 promotes the transcription of NtPDF1.2 and NtJAZ1, but has little effect on the expression of NtPMT1a, quinolinate phosphoribosyltransferase 2 (NtQPT2), and NtMYC2a in tobacco. These results indicate that NtAIDP1 is a new component of the JA signalling pathway and is involved in JA-regulated gene expression.
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Ciclopentanos/metabolismo , Nicotiana/genética , Nicotiana/metabolismo , Oxilipinas/metabolismo , Reguladores del Crecimiento de las Plantas/genética , Reguladores del Crecimiento de las Plantas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Productos Agrícolas/genética , Productos Agrícolas/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
Detection of ultra-weak oscillatory magnetic field changes using MRI is of great research interest not only for neuronal current MRI of endogenous neuronal oscillations but also for direct visualization of exogenous transcranial currents or iron oxide contrast agent distribution. In this work, we present a novel oscillatory-selective detection (OSD) method that is magnitude-sensitive to the oscillatory magnetic field changes and immune to the main field inhomogeneity. In OSD, a train of 180° pulses with alternating polarity and mirror symmetry are used to refocus and accumulate magnetization changes induced by external oscillatory fields. After taking both the signal change and image signal-to-noise ratio (SNR) into account, a final 90° pulse with a phase offset of 45° is applied to store a combination of the current-induced signal change and background magnetization for the subsequent EPI acquisition. Its performance was demonstrated in phantom and human studies, both of which showed much better detection in the comparison with the recently proposed spin-lock oscillatory excitation (SLOE) method. OSD was further successfully applied in imaging transcranial alternating current stimulation (tACS) induced field changes in the human brain. These promising results suggest that OSD can overcome the limitation of field inhomogeneity impeding previous oscillatory current MRI sensitivity and be a viable tool in future tACS study.
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Mapeo Encefálico/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Campos Magnéticos , Imagen por Resonancia Magnética/métodos , Fantasmas de Imagen , Humanos , Relación Señal-RuidoRESUMEN
Jasmonates (JAs) are well-known regulators of stress, defence, and secondary metabolism in plants, with JA perception triggering extensive transcriptional reprogramming, including both activation and/or repression of entire metabolic pathways. We performed RNA sequencing based transcriptomic profiling of tobacco BY-2 cells before and after treatment with methyl jasmonate (MeJA) to identify novel transcriptional regulators associated with alkaloid formation. A total of 107,140 unigenes were obtained through de novo assembly, and at least 33,213 transcripts (31%) encode proteins, in which 3419 transcription factors (TFs) were identified, representing 72 gene families, as well as 840 transcriptional regulators (TRs) distributed among 19 gene families. After MeJA treatment BY-2 cells, 7260 differentially expressed transcripts were characterised, which include 4443 MeJA-upregulated and 2817 MeJA-downregulated genes. Of these, 227 TFs/TRs in 36 families were specifically upregulated, and 102 TFs/TRs in 38 families were downregulated in MeJA-treated BY-2 cells. We further showed that the expression of 12 ethylene response factors and four basic helix-loop-helix factors increased at the transcriptional level after MeJA treatment in BY-2 cells and displayed specific expression patterns in nic mutants with or without MeJA treatments. Our data provide a catalogue of transcripts of tobacco BY-2 cells and benefit future study of JA-modulated regulation of secondary metabolism in tobacco.
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Alcaloides/metabolismo , Ciclopentanos/farmacología , Nicotiana/genética , Oxilipinas/farmacología , Factores de Transcripción/metabolismo , Acetatos/farmacología , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Regulación de la Expresión Génica de las Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Nicotiana/efectos de los fármacosRESUMEN
Detecting the oscillatory currents with a specific frequency distribution may have the potential to make neuronal current MRI (ncMRI) come true. The phase shift or dephasing induced by both positive and negative episodes of oscillatory neuronal currents is likely to be canceled out over the echo time in typical BOLD-contrast fMRI experiments. Based on the contrast of rotary saturation, both of the recently developed spin-locked oscillatory excitation (SLOE) and stimulus-induced rotary saturation (SIRS) pulse sequences have been demonstrated to be able to detect weak oscillatory magnetic fields in phantoms with 3T MR scanners. In this report, through Bloch equation simulation as well as water phantom and anesthetic rats experiments, we comprehensively evaluate and compare the sensitivities of these two methods (SLOE and SIRS) in detecting the oscillatory magnetic fields for both high (100 Hz) and low (10 Hz) oscillation frequencies, while using their respective optimal imaging parameters. In agreement with the theoretical predications, both the simulated and experimental results showed that the SLOE method features a much higher detection sensitivity of weak magnetic fields than that of the SIRS method. SLOE was able to detect applied oscillatory magnetic fields as low as 0.1 nT in a water phantom and 0.5 nT in rat brains and the deteriorated noise levels in rat data may account for the reduced sensitivity in vivo. These promising results form the foundation for direct detection of in vivo neuronal currents using MRI.