Eosu Kim

A carbon nanotube metal semiconductor field effect transistor-based biosensor for detection of amyloid-beta in human serum.

We have developed a carbon nanotube (CNT) film-based biosensor with a metal semiconductor field effect transistor structure (MESFET). A gold top gate was deposited on the middle of the CNT channel and probe antibodies were immobilized on the gold top gate with an antibody-binding protein, protein G or Escherichia coli outer membrane (OM) with autodisplayed Z-domains of protein A. These CNT-MESFET biosensors exhibited a higher sensitivity than the CNT-FET biosensor with probe antibodies immobilized using a chemical linker, since the orientation of immobilized antibodies was controlled by the antibody-binding proteins. In addition, nonspecific binding was effectively inhibited by E. coli OM. Using the CNT-MESFET biosensors with E. coli OM containing Z domain, we detected amyloid-β (Aβ) in human serum, one of the biomarkers for early diagnosis of Alzheimers disease. Aβ at the level of 1 pg/mL in human serum could be measured in real-time and without labeling, which was lower than a limit of detection for plasma Aβ using an enzyme-linked immune sorbent assay. These results suggested that our CNT-MESFET biosensors might be applicable for an early diagnosis of Alzheimers disease.

Developmental Properties of the Hertwig’s Epithelial Root Sheath in Mice

Hertwig’s epithelial root sheath (HERS) plays an important role in tooth root formation. In this study, we examined root formation of the first molar in mice, focusing on cell proliferation, cell death, cell migration, and the expression patterns of the signaling molecules, including glycoproteins and proteoglycans between PN8 and PN26. The number of HERS cells decreased during root formation, although HERS retained total length until PN15. The migration of HERS cells did not occur during root formation. Moreover, the immunopositive reaction of laminin beta-3 and syndecan-1 in HERS indicates that both cell adhesion and cell proliferation are essential for HERS development. Bmp-2, Bmp-4, and Msx-2 were expressed in HERS cells during root formation. We also developed an in vitro culture system for investigating the periodontium and suggest that this system provides an excellent vehicle for full exploration, and hence improved understanding, of the development and regeneration of the periodontium. Together, our results provide a comprehensive model describing the morphogenesis of early root development in vertebrates.

A Preliminary Investigation of α-lipoic Acid Treatment of Antipsychotic Drug-induced Weight Gain in Patients With Schizophrenia

Weight gain and other metabolic disturbances have now become discouraging, major side effects of atypical antipsychotic drugs (AAPDs). The novel strategies required to counteract these serious consequences, however, should avoid modulating the activities of the neurotransmitter receptors involved because those receptors are the therapeutic targets of AAPDs. Adenosine monophosphate-activated protein kinase is an enzyme that plays a pivotal role in energy homeostasis. We hypothesized that &agr;-lipoic acid (ALA), which is known to modulate adenosine monophosphate-activated protein kinase activity in the hypothalamus and peripheral tissues, would ameliorate AAPD-induced weight gain. We describe the case series of a 12-week ALA trial in schizophrenia patients treated with AAPDs. Two of 7 enrolled subjects were dropped from the study because of noncompliance and demand for new medication to treat depressive symptoms, respectively. The mean (SD) weight loss was 3.16 (3.20) kg (P = 0.043, last observation carried forward; median, 3.03 kg; range, 0-8.85 kg). On average, body mass index showed a significant reduction (P = 0.028) over the 12 weeks. During the same period, a statistically significant reduction was also observed in total cholesterol levels (P = 0.042), and there was a weak trend toward the reduction in insulin resistance (homeostasis model assessment of insulin resistance) (P = 0.080). Three subjects reported increased energy subjectively. The total scores on the Brief Psychiatric Rating Scale and the Montgomery-Asberg Depression Rating Scale did not vary significantly during the study. These preliminary data suggest the possibility that ALA can ameliorate the adverse metabolic effects induced by AAPDs. To confirm the benefits of ALA, more extended study is warranted.

Pulp-dentin Regeneration: Current State and Future Prospects

The goal of regenerative endodontics is to reinstate normal pulp function in necrotic and infected teeth that would result in reestablishment of protective functions, including innate pulp immunity, pulp repair through mineralization, and pulp sensibility. In the unique microenvironment of the dental pulp, the triad of tissue engineering would require infection control, biomaterials, and stem cells. Although revascularization is successful in resolving apical periodontitis, multiple studies suggest that it alone does not support pulp-dentin regeneration. More recently, cell-based approaches in endodontic regeneration based on pulpal mesenchymal stem cells (MSCs) have demonstrated promising results in terms of pulp-dentin regeneration in vivo through autologous transplantation. Although pulpal regeneration requires the cell-based approach, several challenges in clinical translation must be overcome—including aging-associated phenotypic changes in pulpal MSCs, availability of tissue sources, and safety and regulation involved with expansion of MSCs in laboratories. Allotransplantation of MSCs may alleviate some of these obstacles, although the long-term stability of MSCs and efficacy in pulp-dentin regeneration demand further investigation. For an alternative source of MSCs, our laboratory developed induced MSCs (iMSCs) from primary human keratinocytes through epithelial-mesenchymal transition by modulating the epithelial plasticity genes. Initially, we showed that overexpression of ΔNp63α, a major isoform of the p63 gene, led to epithelial-mesenchymal transition and acquisition of stem characteristics. More recently, iMSCs were generated by transient knockdown of all p63 isoforms through siRNA, further simplifying the protocol and resolving the potential safety issues of viral vectors. These cells may be useful for patients who lack tissue sources for endogenous MSCs. Further research will elucidate the level of potency of these iMSCs and assess their transdifferentiation capacities into functional odontoblasts when transplanted into the root canal microenvironment.

Organotypic hippocampal slice culture from the adult mouse brain: A versatile tool for translational neuropsychopharmacology

One of the most significant barriers towards translational neuropsychiatry would be an unavailability of living brain tissues. Although organotypic brain tissue culture could be a useful alternative enabling observation of temporal changes induced by various drugs in living brain tissues, a proper method to establish a stable organotypic brain slice culture system using adult (rather than neonatal) hippocampus has been still elusive. In this study, we evaluated our simple method using the serum-free culture medium for successful adult organotypic hippocampal slice culture. Several tens of hippocampal slices from a single adult mouse (3-5 months old) were cultured in serum-free versus serum-containing conventional culture medium for 30 days and underwent various experiments to validate the effects of the existence of serum in the culture medium. Neither the excessive regression of neuronal viability nor metabolic deficiency was observed in the serum-free medium culture in contrast to the serum-containing medium culture. Despite such viability, newly generated immature neurons were scarcely detected in the serum-free culture, suggesting that the original neurons in the brain slice persist rather than being replaced by neurogenesis. Key structural features of in vivo neural tissue constituting astrocytes, neural processes, and pre- and post-synapses were also well preserved in the serum-free culture. In conclusion, using the serum-free culture medium, the adult hippocampal slice culture system will serve as a promising ex vivo tool for various fields of neuroscience, especially for studies on aging-related neuropsychiatric disorders or for high throughput screening of potential agents working against such disorders.

Leukocyte mitochondrial DNA (mtDNA) content is associated with depression in old women

The purpose of this study was to investigate whether mitochondrial DNA (mtDNA) content of peripheral blood leukocyte is related to depression in community-dwelling old women. A total of 142 community-dwelling women, older than 60 years, were included in the study. The mtDNA copy number, which represents the mtDNA content, was measured using real-time PCR methods. Patients with depression defined as the subjects whose 15-question geriatric depression scale (GDS) score was ≥ 8 or who were taking anti-depressant medication. We also measured cognitive function, physical performances (gait speed, chair-stand times, tandem standing times) and metabolic parameters. The depression group had a significantly lower mtDNA copy number than the control group (71.5 vs. 107.3; interquartile range (IQR) = 42.7-116.0 vs. 51.7-202.1; p = 0.028). The Korean version of the mini mental state examination (K-MMSE) score and physical performance score were significantly lower in the depression group than in the control group (p = 0.041, and p = 0.002, respectively). After adjustment for confounding factors using multiple logistic regression analysis, mtDNA copy number was significantly related to depression (p = 0.025). We demonstrated that low leukocyte mtDNA content is related to depression in community dwelling old women. This finding suggests that mitochondrial dysfunction could be a mechanism of geriatric depression.

Technical and clinical aspects of cortisol as a biochemical marker of chronic stress.

Stress is now recognized as a universal premorbid factor associated with many risk factors of various chronic diseases. Acute stress may induce an individual’s adaptive response to environmental demands. However, chronic, excessive stress causes cumulative negative impacts on health outcomes through “allostatic load”. Thus, monitoring the quantified levels of long-term stress mediators would provide a timely opportunity for prevention or earlier intervention of stressrelated chronic illnesses. Although either acute or chronic stress could be quantified through measurement of changes in physiological parameters such as heart rate, blood pressure, and levels of various metabolic hormones, it is still elusive to interpret whether the changes in circulating levels of stress mediators such as cortisol can reflect the acute, chronic, or diurnal variations. Both serum and salivary cortisol levels reveal acute changes at a single point in time, but the overall long-term systemic cortisol exposure is difficult to evaluate due to circadian variations and its protein-binding capacity. Scalp hair has a fairy predictable growth rate of approximately 1 cm/month, and the most 1 cm segment approximates the last month’s cortisol production as the mean value. The analysis of cortisol in hair is a highly promising technique for the retrospective assessment of chronic stress. [BMB Reports 2015; 48(4): 209-216]

Nonverbal social behaviors of patients with bipolar mania during interactions with virtual humans.

It has been proposed that positive emotional biases could make bipolar manic (BM) patients maintain abnormally approaching behaviors during social interactions. To test this hypothesis, we measured interpersonal distance (IPD) and gaze angle of BM patients and normal controls (NCs) during social interaction in immersive virtual environment. Overall, IPDs of BM patients (n = 20) were greater than those of normal controls (n = 20). The IPD difference was even greater between NCs and BM patients with psychotic features (n = 11) than those without psychotic features (n = 9). Regardless of the presence of psychotic features, BM patients averted their gazes more than NCs, and even more while speaking than while listening. Our results might suggest negativistic social cognition of bipolar patients, as was previously found even during a manic phase, or the role of paranoid symptoms in avoidant social behaviors, in agreement with prior studies with schizophrenic patients. Use of proper space and gaze might have psychotherapeutic implication in developing secure, two-person relationship with bipolar patients regardless of the presence of disrupting manic symptoms.

HIV‐associated neurocognitive disorder in HIV‐infected Koreans: the Korean NeuroAIDS Project

HIV‐associated neurocognitive disorder (HAND) is an independent predictor of early mortality and is associated with many difficulties in activities of daily living. We sought to determine the prevalence of and risk factors for HAND in HIV‐infected Koreans. In addition, we investigated the performance of screening tools and components of neuropsychological (NP) tests for diagnosing HAND.

Deficits in eye gaze during negative social interactions in patients with schizophrenia.

Impaired social functioning has been reported in patients with schizophrenia. This study aimed to examine characteristics of interpersonal behaviors in patients with schizophrenia during various social interactions using the virtual reality system. Twenty-six patients and 26 controls engaged in the virtual conversation tasks, including 3 positive and 3 negative emotion-laden conversations. Eye gaze and other behavioral parameters were recorded during the listening and answering phases. The amount of eye gaze was assessed as smaller in the patients than in the controls. A significant interaction effect of group status and emotional type was found for the listening phase. The amount of eye gaze in the patients inversely correlated with self-rated scores of assertiveness for the listening phase. These results suggest that the patients displayed inadequate levels of augmentations in eye gaze during negative emotional situations. These deficits should be considered in the treatment and social skills training for patients with schizophrenia.