Differential inhibitory effects of resveratrol on excitotoxicity and synaptic plasticity: involvement of NMDA receptor subtypes.

Objectives: The neuroprotective effects of resveratrol against excitatory neurotoxicity have been associated with N-methyl-D-aspartate receptor (NMDAR) inhibition. This study examined the differential inhibitory effects of resveratrol on NMDAR-mediated responses in neuronal cells with different NMDAR subtype composition.Methods: The effects of resveratrol on NMDA-induced cell death and calcium influx in immature and mature rat primary cortical neurons were determined and compared. Moreover, the potencies and efficacies of resveratrol to inhibit NR1/NR2A, NR1/NR2B, NR1/NR2C, and NR1/NR2D NMDAR expressed in HEK 293 cells were evaluated.Results: Resveratrol significantly attenuated NMDA-induced cell death in mature neurons, but not in immature neurons. Resveratrol also concentration-dependently reduced NMDA-induced calcium influx among all NMDAR subtypes, but displayed NR2 subunit selectivity, with a potency rank order of NR2B = NR2D > NR2A = NR2C and an efficacy rank order of NR2B = NR2C > NR2A = NR2D. Data show the stronger inhibitory effects of resveratrol on NR1/NR2B than other subtypes. Moreover, resveratrol did not affect hippocampal long-term potentiation (LTP), but impaired long-term depression (LTD).Discussion: These findings reveal the specific NMDAR modulating profile of resveratrol, providing further insight into potential mechanisms underlying the protective effects of resveratrol on neurological disorders.

High-resolution 3D MR Fingerprinting using parallel imaging and deep learning.

MR Fingerprinting (MRF) is a relatively new imaging framework capable of providing accurate and simultaneous quantification of multiple tissue properties for improved tissue characterization and disease diagnosis. While 2D MRF has been widely available, extending the method to 3D MRF has been an actively pursued area of research as a 3D approach can provide a higher spatial resolution and better tissue characterization with an inherently higher signal-to-noise ratio. However, 3D MRF with a high spatial resolution requires lengthy acquisition times, especially for a large volume, making it impractical for most clinical applications. In this study, a high-resolution 3D MR Fingerprinting technique, combining parallel imaging and deep learning, was developed for rapid and simultaneous quantification of T1 and T2 relaxation times. Parallel imaging was first applied along the partition-encoding direction to reduce the amount of acquired data. An advanced convolutional neural network was then integrated with the MRF framework to extract features from the MRF signal evolution for improved tissue characterization and accelerated mapping. A modified 3D-MRF sequence was also developed in the study to acquire data to train the deep learning model that can be directly applied to prospectively accelerate 3D MRF scans. Our results of quantitative T1 and T2 maps demonstrate that improved tissue characterization can be achieved using the proposed method as compared to prior methods. With the integration of parallel imaging and deep learning techniques, whole-brain (26 × 26 × 18 cm3) quantitative T1 and T2 mapping with 1-mm isotropic resolution were achieved in ~7 min. In addition, a ~7-fold improvement in processing time to extract tissue properties was also accomplished with the deep learning approach as compared to the standard template matching method. All of these improvements make high-resolution whole-brain quantitative MR imaging feasible for clinical applications.

Common functional networks in the mouse brain revealed by multi-centre resting-state fMRI analysis.

Preclinical applications of resting-state functional magnetic resonance imaging (rsfMRI) offer the possibility to non-invasively probe whole-brain network dynamics and to investigate the determinants of altered network signatures observed in human studies. Mouse rsfMRI has been increasingly adopted by numerous laboratories worldwide. Here we describe a multi-centre comparison of 17 mouse rsfMRI datasets via a common image processing and analysis pipeline. Despite prominent cross-laboratory differences in equipment and imaging procedures, we report the reproducible identification of several large-scale resting-state networks (RSN), including a mouse default-mode network, in the majority of datasets. A combination of factors was associated with enhanced reproducibility in functional connectivity parameter estimation, including animal handling procedures and equipment performance. RSN spatial specificity was enhanced in datasets acquired at higher field strength, with cryoprobes, in ventilated animals, and under medetomidine-isoflurane combination sedation. Our work describes a set of representative RSNs in the mouse brain and highlights key experimental parameters that can critically guide the design and analysis of future rodent rsfMRI investigations.

Effect of Astaxanthin on the Inhibition of Lipid Accumulation in 3T3-L1 Adipocytes via Modulation of Lipogenesis and Fatty Acid Transport Pathways.

Obesity is defined as a condition of excessive fat tissue accumulation. It was the major factor most closely associated with lifestyle-related diseases. In the present study, we investigated the effect of astaxanthin on the inhibition of lipid accumulation in 3T3-L1 adipocytes. 3T3-L1 adipocytes were treated with 0-25 µg/mL of astaxanthin for 0-48 h. The result indicated that astaxanthin significantly decreased the oil Red O stained material (OROSM), intracellular triglyceride accumulation, and glycerol 3-phosphate dehydrogenase (GPDH) activity in 3T3-L1 adipocytes (p < 0.05). At the molecular level, astaxanthin significantly down-regulated the mRNA expression of peroxisome proliferator-activated receptor-γ (PPARγ) in 3T3-L1 adipocytes (p < 0.05). Moreover, target genes of PPARγ on the inhibition of lipogenesis, such as Acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), fatty acid binding protein (aP2), cluster of differentiation 36 (CD36), and lipoprotein lipase (LPL) in 3T3-L1 adipocytes were significantly down-regulated at a time-dependent manner (p < 0.05). These results suggested that astaxanthin efficiently suppressed lipid accumulation in 3T3-L1 adipocytes and its action is associated with the down-regulation of lipogenesis-related genes and the triglyceride accumulation in 3T3-L1 adipocytes. Therefore, astaxanthin can be developed as a potential nutraceutical ingredient for the prevention of obesity in a niche market.

Evaluation of nuisance removal for functional MRI of rodent brain.

Functional MRI (fMRI) has become an important translational tool for studying brain activity and connectivity in animal models and humans. For accurate and reliable measurement of functional connectivity, nuisance removal strategies developed for human brain, such as regressing motion parameters, cerebrospinal fluid (CSF)/white matter-derived signals and the global signal, have been applied to rodent. However, due to the very different anatomy, with the majority of the rodent brain being gray matter, and experimental conditions, in which animals are anesthetized and head-fixed, these methods may not be suitable for rodent fMRI. In this study, we assessed various nuisance regression methods and the effects of motion correction on a large dataset of both task and resting fMRI of anesthetized rat brain. Sensitivity and specificity were assessed in the somatosensory pathway under forepaw stimulation and resting state. Reproducibility at various sample sizes was simulated by randomly subsampling the dataset. To overcome the difficulty in extracting nuisance from the brain, a method using principal components estimated from tissues outside the brain was evaluated. Our results showed that neither detrend, motion correction, motion regression nor CSF signal regression could improve specificity despite increasing temporal signal-to-noise ratios. Although global signal regression increased the specificity of task activation and functional connectivity, the sensitivity and connectivity strength was drastically reduced, likely due to its strong correlation with the cortical signal. Motion parameters also correlated with task activation and the global signal, indicating that motion correction detected intensity variations in the brain. The nuisance estimated from tissues outside the brain produced a moderate improvement in specificity. In conclusion, nuisance removal suitable for human fMRI may not be optimal for rodents. While further development is needed, estimating nuisance from tissues outside the brain may be an alternative.

Connectomic imaging reveals Huntington-related pathological and pharmaceutical effects in a mouse model.

Recent studies suggest that neurodegenerative diseases could affect brain structure and function in disease-specific network patterns; however, how spontaneous activity affects structural covariance network (SC) is not clear. We hypothesized that hyper-excitability in Huntington disease (HD) disrupts the coordinated structural and functional connectivity, and treatment with memantine helps to reduce excitotoxicity and normalize the connectivity. MRI was conducted to measure somatosensory activation, resting-state functional-connectivity (rsFC), SC, amplitude of low frequency fluctuation (ALFF) and ALFF covariance (ALFFC) in the YAC128 mouse model of HD. We found somatosensory activation was unchanged but the subcortical ALFF was increased in HD mice, indicating subcortical but not cortical hyperactivity. The reduced sensorimotor rsFC but spared hippocampal and default mode networks in the HD mice was consistent with the more pronounced impairment in motor function compared with cognitive performance. The disease suppressed SC globally and reduced ALFFC in the basal ganglia network as well as its anti-correlation with the default mode network. By comparing these connectivity measures, we found that the originally coupled rsFC-SC relationship was impaired whereas SC-ALFFC correlation was increased by HD, suggesting disease facilitated covariation of brain volume and activity amplitude but not neural synchrony. The comparison with mono-synaptic axonal projection supports the hypothesis that rsFC, but not SC or ALFFC, is highly dependent on structural connectivity under healthy conditions. Treatment with memantine had a strong effect on normalizing the SC and reducing ALFF while slightly increasing other connectivity measures and restoring the rsFC-SC coupling, which is consistent with its effect on alleviating hyper-excitability and improving the coordinated neural growth. These results indicate that HD affects the cerebral structure-function relationship which could be partially reverted by NMDA antagonism. These connectivity measures provide unique insights into pathological and pharmaceutical effects in brain circuitry, and could be translatable biomarkers for evaluating drug effect and refining its efficacy.

Suppression of irrelevant sounds during auditory working memory.

Auditory working memory (WM) processing in everyday acoustic environments depends on our ability to maintain relevant information online in our minds, and to suppress interference caused by competing incoming stimuli. A challenge in communication settings is that the relevant content and irrelevant inputs may emanate from a common source, such as a talkative conversationalist. An open question is how the WM system deals with such interference. Will the distracters become inadvertently filtered before processing for meaning because the primary WM operations deplete all available processing resources? Or are they suppressed post perceptually, through an active control process? We tested these alternative hypotheses by measuring magnetoencephalography (MEG), EEG, and functional MRI (fMRI) during a phonetic auditory continuous performance task. Contextual WM maintenance load was manipulated by adjusting the number of "filler" letter sounds in-between cue and target letter sounds. Trial-to-trial variability of pre- and post-stimulus activations in fMRI-informed cortical MEG/EEG estimates was analyzed within and across 14 subjects using generalized linear mixed effect (GLME) models. High contextual WM maintenance load suppressed left auditory cortex (AC) activations around 250-300 ms after the onset of irrelevant phonetic sounds. This effect coincided with increased 10-14 Hz alpha-range oscillatory functional connectivity between the left dorsolateral prefrontal cortex (DLPFC) and left AC. Suppression of AC responses to irrelevant sounds during active maintenance of the task context also correlated with increased pre-stimulus 7-15 Hz alpha power. Our results suggest that under high auditory WM load, irrelevant sounds are suppressed through a "late" active suppression mechanism, which prevents short-term consolidation of irrelevant information without affecting the initial screening of potentially meaningful stimuli. The results also suggest that AC alpha oscillations play an inhibitory role during auditory WM processing.

Deep Sea Water Improves Abnormalities in Lipid Metabolism through Lipolysis and Fatty Acid Oxidation in High-Fat Diet-Induced Obese Rats.

Deep sea water (DSW) is a natural marine resource that has been utilized for food, agriculture, cosmetics, and medicine. The aim of this study was to investigate whether DSW has beneficial lipid metabolic effects in an animal model. Our previous in vitro study indicated that DSW significantly decreased the intracellular triglyceride and glycerol-3-phosphate dehydrogenase activity in 3T3-L1 adipocytes. DSW also inhibited the gene levels of adipocyte differentiation, lipogenesis, and adipocytokines, and up-regulated gene levels of lipolysis and fatty acid oxidation. In the present study, the results showed that body weight, liver, adipose tissue, hepatic triglycerides and cholesterol, and serum parameters in the high-fat diet (HFD) + DSW groups were significantly lower compared to the HFD group. Moreover, the fecal output of total lipids, triglycerides, and cholesterol in the HFD + DSW groups was significantly higher than that of the HFD group. Regarding gene expression, DSW significantly increased the gene levels of lipolysis and fatty acid oxidation, and decreased the gene levels of adipocytokine in the adipose tissue of rats with HFD-induced obesity. These results indicate a potential molecular mechanism by which DSW can suppress obesity in rats with HFD-induced obesity through lipolysis and fatty acid oxidation.

Intracortical depth analyses of frequency-sensitive regions of human auditory cortex using 7TfMRI.

Despite recent advances in auditory neuroscience, the exact functional organization of human auditory cortex (AC) has been difficult to investigate. Here, using reversals of tonotopic gradients as the test case, we examined whether human ACs can be more precisely mapped by avoiding signals caused by large draining vessels near the pial surface, which bias blood-oxygen level dependent (BOLD) signals away from the actual sites of neuronal activity. Using ultra-high field (7T) fMRI and cortical depth analysis techniques previously applied in visual cortices, we sampled 1mm isotropic voxels from different depths of AC during narrow-band sound stimulation with biologically relevant temporal patterns. At the group level, analyses that considered voxels from all cortical depths, but excluded those intersecting the pial surface, showed (a) the greatest statistical sensitivity in contrasts between activations to high vs. low frequency sounds and (b) the highest inter-subject consistency of phase-encoded continuous tonotopy mapping. Analyses based solely on voxels intersecting the pial surface produced the least consistent group results, even when compared to analyses based solely on voxels intersecting the white-matter surface where both signal strength and within-subject statistical power are weakest. However, no evidence was found for reduced within-subject reliability in analyses considering the pial voxels only. Our group results could, thus, reflect improved inter-subject correspondence of high and low frequency gradients after the signals from voxels near the pial surface are excluded. Using tonotopy analyses as the test case, our results demonstrate that when the major physiological and anatomical biases imparted by the vasculature are controlled, functional mapping of human ACs becomes more consistent from subject to subject than previously thought.

Combined MEG and EEG show reliable patterns of electromagnetic brain activity during natural viewing.

Naturalistic stimuli such as movies are increasingly used to engage cognitive and emotional processes during fMRI of brain hemodynamic activity. However, movies have been little utilized during magnetoencephalography (MEG) and EEG that directly measure population-level neuronal activity at a millisecond resolution. Here, subjects watched a 17-min segment from the movie Crash (Lionsgate Films, 2004) twice during simultaneous MEG/EEG recordings. Physiological noise components, including ocular and cardiac artifacts, were removed using the DRIFTER algorithm. Dynamic estimates of cortical activity were calculated using MRI-informed minimum-norm estimation. To improve the signal-to-noise ratio (SNR), principal component analyses (PCA) were employed to extract the prevailing temporal characteristics within each anatomical parcel of the Freesurfer Desikan-Killiany cortical atlas. A variety of alternative inter-subject correlation (ISC) approaches were then utilized to investigate the reliability of inter-subject synchronization during natural viewing. In the first analysis, the ISCs of the time series of each anatomical region over the full time period across all subject pairs were calculated and averaged. In the second analysis, dynamic ISC (dISC) analysis, the correlation was calculated over a sliding window of 200 ms with 3.3 ms steps. Finally, in a between-run ISC analysis, the between-run correlation was calculated over the dynamic ISCs of the two different runs after the Fisher z-transformation. Overall, the most reliable activations occurred in occipital/inferior temporal visual and superior temporal auditory cortices as well as in the posterior cingulate, precuneus, pre- and post-central gyri, and right inferior and middle frontal gyri. Significant between-run ISCs were observed in superior temporal auditory cortices and inferior temporal visual cortices. Taken together, our results show that movies can be utilized as naturalistic stimuli in MEG/EEG similarly as in fMRI studies.

Lateralized parietotemporal oscillatory phase synchronization during auditory selective attention.

Based on the infamous left-lateralized neglect syndrome, one might hypothesize that the dominating right parietal cortex has a bilateral representation of space, whereas the left parietal cortex represents only the contralateral right hemispace. Whether this principle applies to human auditory attention is not yet fully clear. Here, we explicitly tested the differences in cross-hemispheric functional coupling between the intraparietal sulcus (IPS) and auditory cortex (AC) using combined magnetoencephalography (MEG), EEG, and functional MRI (fMRI). Inter-regional pairwise phase consistency (PPC) was analyzed from data obtained during dichotic auditory selective attention task, where subjects were in 10-s trials cued to attend to sounds presented to one ear and to ignore sounds presented in the opposite ear. Using MEG/EEG/fMRI source modeling, parietotemporal PPC patterns were (a) mapped between all AC locations vs. IPS seeds and (b) analyzed between four anatomically defined AC regions-of-interest (ROI) vs. IPS seeds. Consistent with our hypothesis, stronger cross-hemispheric PPC was observed between the right IPS and left AC for attended right-ear sounds, as compared to PPC between the left IPS and right AC for attended left-ear sounds. In the mapping analyses, these differences emerged at 7-13Hz, i.e., at the theta to alpha frequency bands, and peaked in Heschl's gyrus and lateral posterior non-primary ACs. The ROI analysis revealed similarly lateralized differences also in the beta and lower theta bands. Taken together, our results support the view that the right parietal cortex dominates auditory spatial attention.

Improving the spatial resolution of magnetic resonance inverse imaging via the blipped-CAIPI acquisition scheme.

Using simultaneous acquisition from multiple channels of a radio-frequency (RF) coil array, magnetic resonance inverse imaging (InI) achieves functional MRI acquisitions at a rate of 100ms per whole-brain volume. InI accelerates the scan by leaving out partition encoding steps and reconstructs images by solving under-determined inverse problems using RF coil sensitivity information. Hence, the correlated spatial information available in the coil array causes spatial blurring in the InI reconstruction. Here, we propose a method that employs gradient blips in the partition encoding direction during the acquisition to provide extra spatial encoding in order to better differentiate signals from different partitions. According to our simulations, this blipped-InI (bInI) method can increase the average spatial resolution by 15.1% (1.3mm) across the whole brain and from 32.6% (4.2mm) in subcortical regions, as compared to the InI method. In a visual fMRI experiment, we demonstrate that, compared to InI, the spatial distribution of bInI BOLD response is more consistent with that of a conventional echo-planar imaging (EPI) at the level of individual subjects. With the improved spatial resolution, especially in subcortical regions, bInI can be a useful fMRI tool for obtaining high spatiotemporal information for clinical and cognitive neuroscience studies.

Optimal shrinkage denoising breaks the noise floor in high-resolution diffusion MRI.

The spatial resolution attainable in diffusion magnetic resonance (MR) imaging is inherently limited by noise. The weaker signal associated with a smaller voxel size, especially at a high level of diffusion sensitization, is often buried under the noise floor owing to the non-Gaussian nature of the MR magnitude signal. Here, we show how the noise floor can be suppressed remarkably via optimal shrinkage of singular values associated with noise in complex-valued k-space data from multiple receiver channels. We explore and compare different low-rank signal matrix recovery strategies to utilize the inherently redundant information from multiple channels. In combination with background phase removal, the optimal strategy reduces the noise floor by 11 times. Our framework enables imaging with substantially improved resolution for precise characterization of tissue microstructure and white matter pathways without relying on expensive hardware upgrades and time-consuming acquisition repetitions, outperforming other related denoising methods.

Dynamic oscillatory processes governing cued orienting and allocation of auditory attention.

In everyday listening situations, we need to constantly switch between alternative sound sources and engage attention according to cues that match our goals and expectations. The exact neuronal bases of these processes are poorly understood. We investigated oscillatory brain networks controlling auditory attention using cortically constrained fMRI-weighted magnetoencephalography/EEG source estimates. During consecutive trials, participants were instructed to shift attention based on a cue, presented in the ear where a target was likely to follow. To promote audiospatial attention effects, the targets were embedded in streams of dichotically presented standard tones. Occasionally, an unexpected novel sound occurred opposite to the cued ear to trigger involuntary orienting. According to our cortical power correlation analyses, increased frontoparietal/temporal 30-100 Hz gamma activity at 200-1400 msec after cued orienting predicted fast and accurate discrimination of subsequent targets. This sustained correlation effect, possibly reflecting voluntary engagement of attention after the initial cue-driven orienting, spread from the TPJ, anterior insula, and inferior frontal cortices to the right FEFs. Engagement of attention to one ear resulted in a significantly stronger increase of 7.5-15 Hz alpha in the ipsilateral than contralateral parieto-occipital cortices 200-600 msec after the cue onset, possibly reflecting cross-modal modulation of the dorsal visual pathway during audiospatial attention. Comparisons of cortical power patterns also revealed significant increases of sustained right medial frontal cortex theta power, right dorsolateral pFC and anterior insula/inferior frontal cortex beta power, and medial parietal cortex and posterior cingulate cortex gamma activity after cued versus novelty-triggered orienting (600-1400 msec). Our results reveal sustained oscillatory patterns associated with voluntary engagement of auditory spatial attention, with the frontoparietal and temporal gamma increases being best predictors of subsequent behavioral performance.

Whole-head rapid fMRI acquisition using echo-shifted magnetic resonance inverse imaging.

The acquisition time of BOLD contrast functional MRI (fMRI) data with whole-brain coverage typically requires a sampling rate of one volume in 1-3s. Although the volumetric sampling time of a few seconds is adequate for measuring the sluggish hemodynamic response (HDR) to neuronal activation, faster sampling of fMRI might allow for monitoring of rapid physiological fluctuations and detection of subtle neuronal activation timing information embedded in BOLD signals. Previous studies utilizing a highly accelerated volumetric MR inverse imaging (InI) technique have provided a sampling rate of one volume per 100 ms with 5mm spatial resolution. Here, we propose a novel modification of this technique, the echo-shifted InI, which allows TE to be longer than TR, to measure BOLD fMRI at an even faster sampling rate of one volume per 25 ms with whole-brain coverage. Compared with conventional EPI, echo-shifted InI provided an 80-fold speedup with similar spatial resolution and less than 2-fold temporal SNR loss. The capability of echo-shifted InI to detect HDR timing differences was tested empirically. At the group level (n=6), echo-spaced InI was able to detect statistically significant HDR timing differences of as low as 50 ms in visual stimulus presentation. At the level of individual subjects, significant differences in HDR timing were detected for 400 ms stimulus-onset differences. Our results also show that the temporal resolution of 25 ms is necessary for maintaining the temporal detecting capability at this level. With the capabilities of being able to distinguish the timing differences in the millisecond scale, echo-shifted InI could be a useful fMRI tool for obtaining temporal information at a time scale closer to that of neuronal dynamics.

fMRI hemodynamics accurately reflects neuronal timing in the human brain measured by MEG.

Neuronal activation sequence information is essential for understanding brain functions. Extracting such timing information from blood oxygenation level dependent (BOLD) fMRI is confounded by interregional neurovascular differences and poorly understood relations between BOLD and electrophysiological response delays. Here, we recorded whole-head BOLD fMRI at 100 ms resolution and magnetoencephalography (MEG) during a visuomotor reaction-time task. Both methods detected the same activation sequence across five regions, from visual towards motor cortices, with linearly correlated interregional BOLD and MEG response delays. The smallest significant interregional BOLD delay was 100 ms; all delays ≥400 ms were significant. Switching the order of external events reversed the sequence of BOLD activations, indicating that interregional neurovascular differences did not confound the results. This may open new avenues for using fMRI to follow rapid activation sequences in the brain.

Sparse current source estimation for MEG using loose orientation constraints.

Spatially focal source estimates for magnetoencephalography (MEG) and electroencephalography (EEG) data can be obtained by imposing a minimum ℓ(1) -norm constraint on the distribution of the source currents. Anatomical information about the expected locations and orientations of the sources can be included in the source models. In particular, the sources can be assumed to be oriented perpendicular to the cortical surface. We introduce a minimum ℓ(1) -norm estimation source modeling approach with loose orientation constraints (ℓ(1) LOC), which integrates the estimation of the orientation, location, and strength of the source currents into a cost function to jointly model the residual error and the ℓ(1) -norm of the source estimates. Evaluation with simulated MEG data indicated that the ℓ(1) LOC method can provide low spatial dispersion, high localization accuracy, and high source detection rates. Application to somatosensory and auditory MEG data resulted in physiologically reasonable source distributions. The proposed ℓ(1) LOC method appears useful for incorporating anatomical information about the source orientations into sparse source estimation of MEG data.

Basic amino acid residues of human eosinophil derived neurotoxin essential for glycosaminoglycan binding.

Human eosinophil derived neurotoxin (EDN), a granule protein secreted by activated eosinophils, is a biomarker for asthma in children. EDN belongs to the human RNase A superfamily possessing both ribonucleolytic and antiviral activities. EDN interacts with heparin oligosaccharides and heparin sulfate proteoglycans on bronchial epithelial Beas-2B cells. In this study, we demonstrate that the binding of EDN to cells requires cell surface glycosaminoglycans (GAGs), and the binding strength between EDN and GAGs depends on the sulfation levels of GAGs. Furthermore, in silico computer modeling and in vitro binding assays suggest critical roles for the following basic amino acids located within heparin binding regions (HBRs) of EDN 34QRRCKN39 (HBR1), 65NKTRKN70 (HBR2), and 113NRDQRRD119 (HBR3) and in particular Arg35, Arg36, and Arg38 within HBR1, and Arg114 and Arg117 within HBR3. Our data suggest that sulfated GAGs play a major role in EDN binding, which in turn may be related to the cellular effects of EDN.

Enabling brain-wide mapping of directed functional connectivity at 3T via layer-dependent fMRI with draining-vein suppression.

Layer-dependent functional magnetic resonance imaging (fMRI) offers a compelling avenue for investigating directed functional connectivity (FC). To construct a comprehensive map of brain-wide directed FC, several technical criteria must be met, including sub-mm spatial resolution, adequate temporal resolution, functional sensitivity, global brain coverage, and high spatial specificity. Although gradient echo (GE)-based echo planar imaging (EPI) is commonly used for rapid fMRI acquisition, it faces significant challenges due to the draining-vein effect, particularly when utilizing blood oxygen level-dependent (BOLD) contrast. In this study, we mitigated this effect by incorporating velocity-nulling (VN) gradients into a GE-BOLD fMRI sequence, opting for a 3T magnetic field strength over 7T. We also integrated several advanced techniques, such as simultaneous multi-slice (SMS) acceleration and NORDIC denoising, to enhance temporal resolution, spatial coverage, and signal sensitivity. Collectively, the VN fMRI method exhibited notable spatial specificity, as evidenced by the identification of double-peak activation patterns within the primary motor cortex (M1) during a finger-tapping task. Additionally, the technique demonstrated BOLD sensitivity in the lateral geniculate nucleus (LGN). Furthermore, our VN fMRI technique displayed superior robustness when compared to conventional fMRI approaches across participants. Our findings of directed FC elucidate several layer-specific functional relationships between different brain regions and align closely with existing literature. Given the widespread availability of 3T scanners, this technical advancement has the potential for significant impact across multiple domains of neuroscience research.

An Innovative Mei-Gin Formula Exerts Anti-Adipogenic and Anti-Obesity Effects in 3T3-L1 Adipocyte and High-Fat Diet-Induced Obese Rats.

BACKGROUND: To investigate the potential anti-obesity properties of an innovative functional formula (called the Mei-Gin formula: MGF) consisting of bainiku-ekisu, Prunus mume (70% ethanol extract), black garlic (water extract), and Mesona procumbens Hemsl. (40% ethanol extract) for reducing lipid accumulation in 3T3-L1 adipocytes in vitro and obese rats in vivo. MATERIAL AND METHODS: The prevention and regression of high-fat diet (HFD)-induced obesity by the intervention of Japan Mei-Gin, MGF-3 and -7, and positive health supplement powder were investigated in male Wistar rats. The anti-obesity effects of MGF-3 and -7 in rats with HFD-induced obesity were examined by analyzing the role of visceral and subcutaneous adipose tissue in the development of obesity. RESULTS: The results indicated that MGF-1-7 significantly suppressed lipid accumulation and cell differentiation through the down-regulation of GPDH activity, as a key regulator in the synthesis of triglycerides. Additionally, MGF-3 and MGF-7 exhibited a greater inhibitory effect on adipogenesis in 3T3-L1 adipocytes. The high-fat diet increased body weight, liver weight, and total body fat (visceral and subcutaneous fat) in obese rats, while these alterations were effectively improved by the administration of MGF-3 and -7, especially MGF-7. CONCLUSION: This study highlights the role of the Mei-Gin formula, particularly MGF-7, in anti-obesity action, which has the potential to be used as a therapeutic agent for the prevention or treatment of obesity.