• Investigative Magnetic Resonance Imaging
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• v.25 no.3
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• pp.164-171
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• 2021

Purpose: Mild cognitive impairment (MCI) is a prodromal stage of Alzheimer's disease (AD). Brain atrophy in this disease spectrum begins in the medial temporal lobe structure, which can be recognized by magnetic resonance imaging. To overcome the unsatisfactory inter-observer reliability of visual evaluation, quantitative brain volumetry has been developed and widely investigated for the diagnosis of MCI and AD. The aim of this study was to assess the prediction accuracy of quantitative brain volumetry using a fully automated segmentation software package, NeuroQuant^®, for the diagnosis of MCI. Materials and Methods: A total of 418 subjects from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease cohort were included in our study. Each participant was allocated to either a cognitively normal old group (n = 285) or an MCI group (n = 133). Brain volumetric data were obtained from T1-weighted images using the NeuroQuant software package. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to investigate relevant brain regions and their prediction accuracies. Results: Multivariate logistic regression analysis revealed that normative percentiles of the hippocampus (P < 0.001), amygdala (P = 0.003), frontal lobe (P = 0.049), medial parietal lobe (P = 0.023), and third ventricle (P = 0.012) were independent predictive factors for MCI. In ROC analysis, normative percentiles of the hippocampus and amygdala showed fair accuracies in the diagnosis of MCI (area under the curve: 0.739 and 0.727, respectively). Conclusion: Normative percentiles of the hippocampus and amygdala provided by the fully automated segmentation software could be used for screening MCI with a reasonable post-processing time. This information might help us interpret structural MRI in patients with cognitive impairment.

• Molecules and Cells
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• v.39 no.11
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• pp.783-789
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• 2016

Afflicted neurons in various neurodegenerative diseases generally display diverse and complex pathological features before catastrophic occurrence of massive neuronal loss at the late stages of the diseases. This complex nature of neuronal pathophysiology inevitably implicates systemwide changes in basic cellular activities such as transcriptional controls and signal cascades, and so on, as a cause. Recently, as one of these systemwide cellular changes associated with neurodegenerative diseases, epigenetic changes caused by protein toxicity have begun to be highlighted. Notably, recent advances in related techniques including next-generation sequencing (NGS) and mass spectrometry enable us to monitor changes in the post-translational modifications (PTMs) of histone proteins and to link these changes in histone PTMs to the specific transcriptional changes. Indeed, epigenetic alterations and consequent changes in neuronal transcriptome are now begun to be extensively studied in neurodegenerative diseases including Alzheimer's disease (AD). In this review, we will discuss details of our current understandings on epigenetic changes associated with two representative neurodegenerative diseases [AD and polyglutamine (polyQ) diseases] and further discuss possible future development of pharmaceutical treatment of the diseases through modulating these epigenetic changes.

• Molecules and Cells
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• v.27 no.6
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• pp.689-695
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• 2009

Chemically synthesized small interfering RNAs (siRNAs) can specifically knock-down expression of target genes via RNA interference (RNAi) pathway. To date, the length of synthetic siRNA duplex has been strictly maintained less than 30 bp, because an early study suggested that double-stranded RNAs (dsRNAs) longer than 30 bp could not trigger specific gene silencing due to the induction of non-specific antiviral interferon responses. Contrary to the current belief, here we show that synthetic dsRNA as long as 38 bp can result in specific target gene silencing without non-specific antiviral responses. Using this longer duplex structure, we have generated dsRNAs, which can simultaneously knock-down expression of two target genes (termed as dual-target siRNAs or dsiRNAs). Our results thus demonstrate the structural flexibility of gene silencing siRNAs, and provide a starting point to construct multifunctional RNA structures. The dsiRNAs could be utilized to develop a novel therapeutic gene silencing strategy against diseases with multiple gene alternations such as viral infection and cancer.

• Reproductive and Developmental Biology
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• v.34 no.3
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• pp.153-159
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• 2010

The 34 potently pig pheromonal odorants (1-32, 5755 & 7113) through structure-based virtual screening and ligand-based virtual screening method were selected and their ADMET and pharmacokinetics characters were evaluated and discussed quantitatively. The pheromonal odorants were projected on the following pre-calculated models, Caco-2 cell permeability, blood-brain barrier permeation, hERG inhibition and volume-distribution. From the results of in silico study, it is found that an optimal compound (31) either penetrating or have a little ($P_{caco2}$=-8.143) for Caco-2 cell permeability, moderate penetrating ability ($P_{BBB}$=0.082) for blood-brain barrier permeation, the low QT prolongation ($P_{hERG}$=1.137) for the hERG $K^+$ channel inhibition, and low distribution into tissues ($P_{VD}$=-5.468) for volume-distribution. Therefore, it is predicted that the compound (31) a topical application may be preferable from these based foundings.

• Korean Journal of Biological Psychiatry
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• v.15 no.4
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• pp.254-264
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• 2008

Objectives : The neural substrate of fear is thought to be highly conserved among species including human. The purpose of this review was to address the neural substrates of fear based on recent findings obtained from animal and human studies. Methods : Recent studies on brain regions related to fear, particularly fear conditioning in rodents and humans, were extensively reviewed. Results : This paper suggests high consistency in anatomical structure and physiological mechanisms for fear perception, response, learning and modulation in animals and humans. Conclusions : Fear is manifested and modulated by well conserved neural circuits among species interconnected with the amygdala, such as the hippocampus and the ventromedial prefrontal cortex. Further research is required to incorporate findings from animal studies into a better understanding of neural circuitry of fear in human in a translational approach.

• Biomolecules & Therapeutics
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• v.20 no.2
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• pp.133-143
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• 2012

Matrix metalloproteinases (MMPs) are a subfamily of zinc-dependent proteases that are re-sponsible for degradation and remodeling of extracellular matrix proteins. The activity of MMPs is tightly regulated at several levels including cleavage of prodomain, allosteric activation, com-partmentalization and complex formation with tissue inhibitor of metalloproteinases (TIMPs). In the central nervous system (CNS), MMPs play a wide variety of roles ranging from brain devel-opment, synaptic plasticity and repair after injury to the pathogenesis of various brain disorders. Following general discussion on the domain structure and the regulation of activity of MMPs, we emphasize their implication in various brain disorder conditions such as Alzheimer's disease, multiple sclerosis, ischemia/reperfusion and Parkinson's disease. We further highlight accumu-lating evidence that MMPs might be the culprit in Parkinson's disease (PD). Among them, MMP-3 appears to be involved in a range of pathogenesis processes in PD including neuroinflamma-tion, apoptosis and degradation of ${\alpha}$-synuclein and DJ-1. MMP inhibitors could represent poten-tial novel therapeutic strategies for treatments of neurodegenerative diseases.

• Journal of Biomedical Engineering Research
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• v.18 no.4
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• pp.421-428
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• 1997

Magnetic field sensors made from superconducting quantum interference device (SQUID) are the most sensitive low-frequency sensors available, enabling measurements of extremely weak magnetic fields from the brain. Neuromagnetic measurements allow superior spatial resolution, compared with the present electric measurements, and superior temporal resolution, compared with the fMRl and PET, providing useful informations for the functional diagnoses of the brain. We developed a 4-channel SQUID system for neuromagnetic applications. The main features of the system are its simple readout electronics and compact pickup coil structure. A magnetically shielded room has been constructed for the reduction of environmental magnetic noises. The developed SQUID system has noise level lower than the magnetic noise from the brain. Magnetic field signals of the spontaneous r-rhythm activity and auditory evoked magnetic fields have been measured.

• Structural Engineering and Mechanics
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• v.87 no.4
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• pp.305-315
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• 2023

The idea of the combination of the fractional-order operators with the brain emotional learning-based intelligent controller (BELBIC) is developed for implementation in seismic-excited structures equipped with active mass damper (AMD). For this purpose, a new design framework of the mentioned combination namely fractional-order BEBIC (FOBELBIC) is proposed based on a modified-teaching-learning-based optimization (MTLBO) algorithm. The seismic performance of the proposed controller is then evaluated for a 15-story building equipped with AMD subjected to two far-field and two near-field earthquakes. An optimal BELBIC based on the MTLBO algorithm is also introduced for comparison purposes. In comparison with the structure equipped with a passive tuned mass damper (TMD), an average reduction of 44.7% and 42.8% are obtained in terms of the maximum absolute and RMS top floor displacement for FOBELBIC, while these reductions are obtained as 30.4% and 30.1% for the optimal BELBIC, respectively. Similarly, the optimal FOBELBIC results in an average reduction of 42.6% and 39.4% in terms of the maximum absolute and RMS top floor acceleration, while these reductions are given as 37.9% and 30.5%, for the optimal BELBIC, respectively. Consequently, the superiority of the FOBELBIC over the BELBIC is concluded in the reduction of maximum and RMS seismic responses.

• Journal of the Korean Magnetic Resonance Society
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• v.2 no.2
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• pp.131-140
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• 1998

The calcium-induced structural changes in the skeletal muscle regulatory protein troponin C (NTnC) involve a transition from a ‘closed’to an ‘open’structure with the concomitant exposure of a large hydrophobic interaction site for target proteins. Structural studies have served to define this conformational change and elucidate the mechanism of the linkage between calcium binding and the induced structural changes. There are now several structures of NTnC available from both NMR and X-ray crystallography. Comparison of the calcium bound structures reveals differences in the level of opening. We have considered the concept of a flexible open state of NTnC as a possible explanation for this apparent discrepancy. We also present simulations of the closed-to-open transition which are in agreement with the flexibility concept and with experimental energetics data.

• Journal of Power Electronics
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• v.14 no.1
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• pp.74-81
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• 2014

In this study, a brain emotional learning-based intelligent controller (BELBIC) is developed for the speed control of an interior permanent magnet synchronous motor (IPMSM). A novel and simple model of the IPMSM drive structure is established with the intelligent control system, which controls motor speed accurately without the use of any conventional PI controllers and is independent of motor parameters. This study is conducted in both real time and simulation with a new control plant for a laboratory 3 ph, 3.8 Nm IPMSM digital signal processor (DSP)-based drive system. This DSP-based drive system is then compared with conventional BELBIC and an optimized conventional PI controller. Results show that the proposed method performs better than the other controllers and exhibits excellent control characteristics, such as fast response, simple implementation, and robustness with respect to disturbances and manufacturing imperfections.