Baf-mediated transcriptional regulation of teashirt is essential for the development of neural progenitor cell lineages.

Accumulating evidence hints heterochromatin anchoring to the inner nuclear membrane as an upstream regulatory process of gene expression. Given that the formation of neural progenitor cell lineages and the subsequent maintenance of postmitotic neuronal cell identity critically rely on transcriptional regulation, it seems possible that the development of neuronal cells is influenced by cell type-specific and/or context-dependent programmed regulation of heterochromatin anchoring. Here, we explored this possibility by genetically disrupting the evolutionarily conserved barrier-to-autointegration factor (Baf) in the Drosophila nervous system. Through single-cell RNA sequencing, we demonstrated that Baf knockdown induces prominent transcriptomic changes, particularly in type I neuroblasts. Among the differentially expressed genes, our genetic analyses identified teashirt (tsh), a transcription factor that interacts with beta-catenin, to be closely associated with Baf knockdown-induced phenotypes that were suppressed by the overexpression of tsh or beta-catenin. We also found that Baf and tsh colocalized in a region adjacent to heterochromatin in type I NBs. Notably, the subnuclear localization pattern remained unchanged when one of these two proteins was knocked down, indicating that both proteins contribute to the anchoring of heterochromatin to the inner nuclear membrane. Overall, this study reveals that the Baf-mediated transcriptional regulation of teashirt is a novel molecular mechanism that regulates the development of neural progenitor cell lineages.

Potential use of polydimethylsiloxane phantom in acupuncture manipulation practice.

Objectives: Sufficient trials of acupuncture manipulations should be practiced to obtain proficiency. However, there is not an adequate quantitative methodology for selecting a tissue-mimicking phantom that effectively reproduces the mechanical behavior that occurs during acupuncture. The objective of this study was to determine the proper mixing ratio of polydimethylsiloxane (PDMS) to obtain tissue phantom that is the most similar to porcine phantoms. Design: An automatic needle manipulator equipped with a six-degrees-of-freedom force/torque sensor was installed to monitor the interaction force that occurred when the acupuncture needle performed lifting-thrusting and twirling manipulations. Four types of PDMS phantoms, composed of two silicone elastomers with different hardener ratios, were studied alongside four control groups consisting of different porcine sites. A Visual Analog Scale was used to quantify the similarity of the PDMS phantoms to the controls by 11 Korean medical doctors. Results: Using the lifting-thrusting method, PDMS D (mixing ratio of 1:4.5) and control 2 (porcine blade shoulder) revealed no significant difference in the dynamic friction coefficients or maximum and minimum friction force values (P < 0.001). Using the twirling method, PDMS D showed no significant difference from all controls in the viscosity coefficient or maximum and minimum torque values (P ≤ 0.001). By practitioners, PDMS D showed the greatest score. Conclusion: PDMS D delivered a haptic sensation that is most similar to that of biological tissues in the case of acu-needle lifting-thrusting and twirling methods. This finding guides the preparation of tissue phantoms for acu-needle studies and acupuncture training.

Endowing a NAO Robot With Practical Social-Touch Perception.

Social touch is essential to everyday interactions, but current socially assistive robots have limited touch-perception capabilities. Rather than build entirely new robotic systems, we propose to augment existing rigid-bodied robots with an external touch-perception system. This practical approach can enable researchers and caregivers to continue to use robotic technology they have already purchased and learned about, but with a myriad of new social-touch interactions possible. This paper presents a low-cost, easy-to-build, soft tactile-perception system that we created for the NAO robot, as well as participants' feedback on touching this system. We installed four of our fabric-and-foam-based resistive sensors on the curved surfaces of a NAO's left arm, including its hand, lower arm, upper arm, and shoulder. Fifteen adults then performed five types of affective touch-communication gestures (hitting, poking, squeezing, stroking, and tickling) at two force intensities (gentle and energetic) on the four sensor locations; we share this dataset of four time-varying resistances, our sensor patterns, and a characterization of the sensors' physical performance. After training, a gesture-classification algorithm based on a random forest identified the correct combined touch gesture and force intensity on windows of held-out test data with an average accuracy of 74.1%, which is more than eight times better than chance. Participants rated the sensor-equipped arm as pleasant to touch and liked the robot's presence significantly more after touch interactions. Our promising results show that this type of tactile-perception system can detect necessary social-touch communication cues from users, can be tailored to a variety of robot body parts, and can provide HRI researchers with the tools needed to implement social touch in their own systems.

The Perspectives of Early Diagnosis of Schizophrenia Through the Detection of Epigenomics-Based Biomarkers in iPSC-Derived Neurons.

The lack of early diagnostic biomarkers for schizophrenia greatly limits treatment options that deliver therapeutic agents to affected cells at a timely manner. While previous schizophrenia biomarker research has identified various biological signals that are correlated with certain diseases, their reliability and practicality as an early diagnostic tool remains unclear. In this article, we discuss the use of atypical epigenetic and/or consequent transcriptional alterations (ETAs) as biomarkers of early-stage schizophrenia. Furthermore, we review the viability of discovering and applying these biomarkers through the use of cutting-edge technologies such as human induced pluripotent stem cell (iPSC)-derived neurons, brain models, and single-cell level analyses.

Astrocytic Regulation of Neural Circuits Underlying Behaviors.

Astrocytes, characterized by a satellite-like morphology, are the most abundant type of glia in the central nervous system. Their main functions have been thought to be limited to providing homeostatic support for neurons, but recent studies have revealed that astrocytes actually actively interact with local neural circuits and play a crucial role in information processing and generating physiological and behavioral responses. Here, we review the emerging roles of astrocytes in many brain regions, particularly by focusing on intracellular changes in astrocytes and their interactions with neurons at the molecular and neural circuit levels.

Red cell manufacturing using parallel stirred-tank bioreactors at the final stages of differentiation enhances reticulocyte maturation.

The aim of this study was to develop a robust, quality controlled, and reproducible erythroid culture system to obtain high numbers of mature erythroblasts and red blood cells (RBCs). This was achieved using a fully controlled stirred-tank bioreactor by the design of experiments (DOE) methods in the serum-free medium by defining the appropriate culture parameters. Human cord blood CD34+ cells were first cultured in static flasks and then inoculated to stirred-tank bioreactors. Cell diameter was gradually decreased and final RBC yields were significantly higher when cells were inoculated at sizes smaller than 12 µm. The larger immature cells in the basophilic stage did not survive, while smaller mature erythroid cells were successfully expanded at high agitation speeds, demonstrating that appropriate seeding timing is critical. A high inoculation cell density of 5 × 106 cells/ml was achieved reaching 1.5 × 107 cells/ml. By using DOE analysis fitted to precise stages of erythropoiesis, we were able to acquire the optimal culture parameters for pH (7.5), temperature (37°C), dissolved oxygen, agitation speed (500 rpm), inoculation timing (cell diameter 12-13 µm), media feeding regimen, and cell seeding density (5 × 106 cells/ml). The final pure RBCs showed appropriate functions compared with fresh donor RBCs, confirming that manufacturing mature RBCs with reproducibility is possible.

Correlation between private education costs and parental depression in South Korea.

BACKGROUND: In Korea, higher education has rapidly grown influenced by sociocultural tradition. Parents invest a significant portion of their household income in their children's education. Private education has been considered to greatly affect students' psychology and behavior. However, past research has largely neglected to study parents who pay these costs. Since household income and education level are important determinants of socioeconomic status (SES), education expenditures are likely to cause depressive symptoms. Therefore, the study aimed to investigate the correlation between private education costs and parental depression in South Korea. METHODS: Data were collected from the Korean Welfare Panel Study (KoWePS, 2015, 2018). The sample analyzed consisted of 397 and 337 fathers and 403 and 370 mothers in 2015 and 2018, respectively. The independent variable in this study was the proportion of private education cost. This proportion was calculated by dividing each household's private education costs by its equivalized household disposable income (EHDI) and multiplying this number by 100. The main dependent variable was parental responses to the Center for Epidemiologic Studies Depression Scale-11 (CESD-11). Using a generalized linear model, we investigated the effects of the proportion of private education cost on parental depression. RESULTS: The results showed that fathers with higher proportions of private education cost exhibited higher CESD-11 scores compared to fathers with lower proportions cost (moderate: ß = 0.419, S. E = 0.164, p = 0.0105; high: ß = 0.476, S. E = 0.178, p = 0.0076), indicating that a higher ratio of private education cost may negatively affect depression in fathers. However, there was no discernable correlation between mothers' CESD-11 scores and the proportion of private education cost (moderate: ß = - 0.078, S. E = 0.250, p = 0.7555; high: ß = 0.003, S. E = 0.215, p = 0.9882). CONCLUSIONS: These results may be explained by the tendency for fathers to experience greater economic burdens than mothers in patriarchal Korean society.

Risks of suicide attempts after prescription of zolpidem in people with depression: a nationwide population study in South Korea.

OBJECTIVES: To investigate the association between zolpidem prescription and suicide attempts in people with depression. METHODS: A nationwide, population-based electronic medical records database from the Health Insurance Review & Assessment Service of South was used to investigate the incidence rate ratios (IRRs) of suicide attempts and probable suicide attempts in people with depression before and after zolpidem prescription using self-controlled case series design. RESULTS: In a total of 445 people who attempted suicide and 23 141 people who attempted probable suicide attempt, the IRRs of suicidal behavior during the risk periods before and after zolpidem prescription increased compared with those at the baseline. The IRRs gradually increased and peaked immediately before the prescription of zolpidem. The IRR was 70.06 (95% CI: 25.58-191.90) on day 2 before zolpidem prescription and 63.35 (95% CI: 22.99-174.59) on day 1 after zolpidem prescription in the suicide attempt group. The IRR was 24.07 (95% CI: 20.50-28.26) on the day before zolpidem prescription and 14.96 (95% CI: 12.21-18.34) on the day after zolpidem prescription in the probable suicide attempt group. The ratios declined eventually after zolpidem was prescribed. CONCLUSIONS: Although zolpidem prescription was associated with an increased risk of suicide attempts in people with depression, the risk increased and peaked immediately before zolpidem prescription. The risk declined gradually thereafter. This result indicates that the risk of suicide attempts increases at the time of zolpidem prescription. However, zolpidem prescription does not contribute to additional increase in the risk of suicide attempts.

Ethanol Elevates Excitability of Superior Cervical Ganglion Neurons by Inhibiting Kv7 Channels in a Cell Type-Specific and PI(4,5)P2-Dependent Manner.

Alcohol causes diverse acute and chronic symptoms that often lead to critical health problems. Exposure to ethanol alters the activities of sympathetic neurons that control the muscles, eyes, and blood vessels in the brain. Although recent studies have revealed the cellular targets of ethanol, such as ion channels, the molecular mechanism by which alcohol modulates the excitability of sympathetic neurons has not been determined. Here, we demonstrated that ethanol increased the discharge of membrane potentials in sympathetic neurons by inhibiting the M-type or Kv7 channel consisting of the Kv7.2/7.3 subunits, which were involved in determining the membrane potential and excitability of neurons. Three types of sympathetic neurons, classified by their threshold of activation and firing patterns, displayed distinct sensitivities to ethanol, which were negatively correlated with the size of the Kv7 current that differs depending on the type of neuron. Using a heterologous expression system, we further revealed that the inhibitory effects of ethanol on Kv7.2/7.3 currents were facilitated or diminished by adjusting the amount of plasma membrane phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). These results suggested that ethanol and PI(4,5)P2 modulated gating of the Kv7 channel in superior cervical ganglion neurons in an antagonistic manner, leading to regulation of the membrane potential and neuronal excitability, as well as the physiological functions mediated by sympathetic neurons.

Rapid resensitization of ASIC2a is conferred by three amino acid residues in the N terminus.

Acid-sensing ion channels (ASICs), sensory molecules that continuously monitor the concentration of extracellular protons and initiate diverse intracellular responses through an influx of cations, are assembled from six subtypes that can differentially combine to form various trimeric channel complexes and elicit unique electrophysiological responses. For instance, homomeric ASIC1a channels have been shown to exhibit prolonged desensitization, and acid-evoked currents become smaller when the channels are repeatedly activated by extracellular protons, whereas homomeric or heteromeric ASIC2a channels continue to respond to repetitive acidic stimuli without exhibiting such desensitization. Although previous studies have provided evidence that both the desensitization of ASIC1a and rapid resensitization of ASIC2a commonly require domains that include the N terminus and the first transmembrane region of these channels, the biophysical basis of channel gating at the amino acid level has not been clearly determined. Here, we confirm that domain-swapping mutations replacing the N terminus of ASIC2a with that of ASIC2b result in de novo prolonged desensitization in homomeric channels following activation by extracellular protons. Such desensitization of chimeric ASIC2a mutants is due neither to internalization nor to degradation of the channel proteins. We use site-directed mutagenesis to narrow down the relevant portion of the N terminus of ASIC2a, identifying three amino acid residues within the N terminus (T25, T39, and I40) whose mutation is sufficient to phenocopy the desensitization exhibited by the chimeric mutants. A similar desensitization is observed in heteromeric ASICs containing the mutant subunit. These results suggest that T25, T39, and I40 of ASIC2a are key residues determining the rapid resensitization of homomeric and heteromeric ASIC2a channels upon proton activation.

Machine-Learning Based Automatic and Real-time Detection of Mouse Scratching Behaviors.

Scratching is a main behavioral response accompanied by acute and chronic itch conditions, and has been quantified as an objective correlate to assess itch in studies using laboratory animals. Scratching has been counted mostly by human annotators, which is a time-consuming and laborious process. It has been attempted to develop automated scoring methods using various strategies, but they often require specialized equipment, costly software, or implantation of device which may disturb animal behaviors. To complement limitations of those methods, we have adapted machine learning-based strategy to develop a novel automated and real-time method detecting mouse scratching from experimental movies captured using monochrome cameras such as a webcam. Scratching is identified by characteristic changes in pixels, body position, and body size by frame as well as the size of body. To build a training model, a novel two-step J48 decision tree-inducing algorithm along with a C4.5 post-pruning algorithm was applied to three 30-min video recordings in which a mouse exhibits scratching following an intradermal injection of a pruritogen, and the resultant frames were then used for the next round of training. The trained method exhibited, on average, a sensitivity and specificity of 95.19% and 92.96%, respectively, in a performance test with five new recordings. This result suggests that it can be used as a non-invasive, automated and objective tool to measure mouse scratching from video recordings captured in general experimental settings, permitting rapid and accurate analysis of scratching for preclinical studies and high throughput drug screening.

Cost-Effectiveness Analysis of Cervical Anterior Fusion and Cervical Artificial Disc Replacement in the Korean Medical System.

OBJECTIVE: This study is a retrospective cost-benefit analysis of cervical anterior interbody fusion and cervical artificial disc replacement, which are the main surgical methods to treat degenerative cervical disc disease. METHODS: We analyzed 156 patients who underwent anterior cervical disc fusion and cervical artificial disc replacement from January 1, 2008 to December 31, 2009, diagnosed with degenerative cervical disc disorder. In this study, the costs and benefits were analyzed by using quality adjusted life year (QALY) as the outcome index for patients undergoing surgery, and a Markov model was used for the analysis. Only direct medical costs were included in the analysis; indirect medical costs were excluded. Data were analyzed with TreeAge Pro 2015™ (TreeAge Software, Inc, Williamstown, MA, USA). RESULTS: Patients who underwent cervical anterior fusion had a total cost of KRW 2501807/USD 2357 over 5 years and obtained a utility of 3.72 QALY. Patients who underwent cervical artificial disc replacement received 4.18 QALY for a total of KRW 3685949/USD 3473 over 5 years. The cumulative cost-effectiveness ratio of cervical spine replacement surgery was KRW 2549511/QALY (USD 2402/QALY), which was lower than the general Korean payment standard. CONCLUSION: Both cervical anterior fusion and cervical artificial disc replacement are cost-effective treatments for patients with degenerative cervical disc disease. Cervical artificial disc replacement may be an effective alternative to obtain more benefits.

Mechanisms of protein toxicity in neurodegenerative diseases.

Protein toxicity can be defined as all the pathological changes that ensue from accumulation, mis-localization, and/or multimerization of disease-specific proteins. Most neurodegenerative diseases manifest protein toxicity as one of their key pathogenic mechanisms, the details of which remain unclear. By systematically deconstructing the nature of toxic proteins, we aim to elucidate and illuminate some of the key mechanisms of protein toxicity from which therapeutic insights may be drawn. In this review, we focus specifically on protein toxicity from the point of view of various cellular compartments such as the nucleus and the mitochondria. We also discuss the cell-to-cell propagation of toxic disease proteins that complicates the mechanistic understanding of the disease progression as well as the spatiotemporal point at which to therapeutically intervene. Finally, we discuss selective neuronal vulnerability, which still remains largely enigmatic.

Development of an MR-compatible hand exoskeleton that is capable of providing interactive robotic rehabilitation during fMRI imaging.

Following advances in robotic rehabilitation, there have been many efforts to investigate the recovery process and effectiveness of robotic rehabilitation procedures through monitoring the activation status of the brain. This work presents the development of a two degree-of-freedom (DoF) magnetic resonance (MR)-compatible hand device that can perform robotic rehabilitation procedures inside an fMRI scanner. The device is capable of providing real-time monitoring of the joint angle, angular velocity, and joint force produced by the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of four fingers. For force measurement, a custom reflective optical force sensor was developed and characterized in terms of accuracy error, hysteresis, and repeatability in the MR environment. The proposed device consists of two non-magnetic ultrasonic motors to provide assistive and resistive forces to the MCP and PIP joints. With actuation and sensing capabilities, both non-voluntary-passive movements and active-voluntary movements can be implemented. The MR compatibility of the device was verified via the analysis of the signal-to-noise ratio (SNR) of MR images of phantoms. SNR drops of 0.25, 2.94, and 11.82% were observed when the device was present but not activated, when only the custom force sensor was activated, and when both the custom force sensor and actuators were activated, respectively.

Esr1+ cells in the ventromedial hypothalamus control female aggression.

As an essential means of resolving conflicts, aggression is expressed by both sexes but often at a higher level in males than in females. Recent studies suggest that cells in the ventrolateral part of the ventromedial hypothalamus (VMHvl) that express estrogen receptor-α (Esr1) and progesterone receptor are essential for male but not female mouse aggression. In contrast, here we show that VMHvlEsr1+ cells are indispensable for female aggression. This population was active when females attacked naturally. Inactivation of these cells reduced female aggression whereas their activation elicited attack. Additionally, we found that female VMHvl contains two anatomically distinguishable subdivisions that showed differential gene expression, projection and activation patterns after mating and fighting. These results support an essential role of the VMHvl in both male and female aggression and reveal the existence of two previously unappreciated subdivisions in the female VMHvl that are involved in distinct social behaviors.

Application of Functional Near-Infrared Spectroscopy to the Study of Brain Function in Humans and Animal Models.

Functional near-infrared spectroscopy (fNIRS) is a noninvasive optical imaging technique that indirectly assesses neuronal activity by measuring changes in oxygenated and deoxygenated hemoglobin in tissues using near-infrared light. fNIRS has been used not only to investigate cortical activity in healthy human subjects and animals but also to reveal abnormalities in brain function in patients suffering from neurological and psychiatric disorders and in animals that exhibit disease conditions. Because of its safety, quietness, resistance to motion artifacts, and portability, fNIRS has become a tool to complement conventional imaging techniques in measuring hemodynamic responses while a subject performs diverse cognitive and behavioral tasks in test settings that are more ecologically relevant and involve social interaction. In this review, we introduce the basic principles of fNIRS and discuss the application of this technique in human and animal studies.

Soft Nanocomposite Based Multi-point, Multi-directional Strain Mapping Sensor Using Anisotropic Electrical Impedance Tomography.

The practical utilization of soft nanocomposites as a strain mapping sensor in tactile sensors and artificial skins requires robustness for various contact conditions as well as low-cost fabrication process for large three dimensional surfaces. In this work, we propose a multi-point and multi-directional strain mapping sensor based on multiwall carbon nanotube (MWCNT)-silicone elastomer nanocomposites and anisotropic electrical impedance tomography (aEIT). Based on the anisotropic resistivity of the sensor, aEIT technique can reconstruct anisotropic resistivity distributions using electrodes around the sensor boundary. This strain mapping sensor successfully estimated stretch displacements (error of 0.54 ± 0.53 mm), surface normal forces (error of 0.61 ± 0.62 N), and multi-point contact locations (error of 1.88 ± 0.95 mm in 30 mm × 30 mm area for a planar shaped sensor and error of 4.80 ± 3.05 mm in 40 mm × 110 mm area for a three dimensional contoured sensor). In addition, the direction of lateral stretch was also identified by reconstructing anisotropic distributions of electrical resistivity. Finally, a soft human-machine interface device was demonstrated as a practical application of the developed sensor.

Optogenetic and Chemogenetic Approaches for Studying Astrocytes and Gliotransmitters.

The brain consists of heterogeneous populations of neuronal and non-neuronal cells. The revelation of their connections and interactions is fundamental to understanding normal brain functions as well as abnormal changes in pathological conditions. Optogenetics and chemogenetics have been developed to allow functional manipulations both in vitro and in vivo to examine causal relationships between cellular changes and functional outcomes. These techniques are based on genetically encoded effector molecules that respond exclusively to exogenous stimuli, such as a certain wavelength of light or a synthetic ligand. Activation of effector molecules provokes diverse intracellular changes, such as an influx or efflux of ions, depolarization or hyperpolarization of membranes, and activation of intracellular signaling cascades. Optogenetics and chemogenetics have been applied mainly to the study of neuronal circuits, but their use in studying non-neuronal cells has been gradually increasing. Here we introduce recent studies that have employed optogenetics and chemogenetics to reveal the function of astrocytes and gliotransmitters.

The peripheral and central mechanisms underlying itch.

Itch is one of the most distressing sensations that substantially impair quality of life. It is a cardinal symptom of many skin diseases and is also caused by a variety of systemic disorders. Unfortunately, currently available itch medications are ineffective in many chronic itch conditions, and they often cause undesirable side effects. To develop novel therapeutic strategies, it is essential to identify primary afferent neurons that selectively respond to itch mediators as well as the central nervous system components that process the sensation of itch and initiate behavioral responses. This review summarizes recent progress in the study of itch, focusing on itch-selective receptors, signaling molecules, neuronal pathways from the primary sensory neurons to the brain, and potential decoding mechanisms based on which itch is distinguished from pain. [BMB Reports 2016; 49(9): 474-487].

Enhancement of charge transport properties of small molecule semiconductors by controlling fluorine substitution and effects on photovoltaic properties of organic solar cells and perovskite solar cells.

We prepared a series of small molecules based on 7,7'-(4,4-bis(2-ethylhexyl)-4H-silolo[3,2-b:4,5-b']dithiophene-2,6-diyl)bis(4-(5'-hexyl-[2,2'-bithiophene]-5-yl)benzo[c][1,2,5]thiadiazole) with different fluorine substitution patterns (0F-4F). Depending on symmetricity and numbers of fluorine atoms incorporated in the benzo[c][1,2,5]thiadiazole unit, they show very different optical and morphological properties in a film. 2F and 4F, which featured symmetric and even-numbered fluorine substitution patterns, display improved molecular packing structures and higher crystalline properties in a film compared with 1F and 3F and thus, 2F achieved the highest OTFT mobility, which is followed by 4F. In the bulk heterojunction solar cell fabricated with PC71BM, 2F achieves the highest photovoltaic performance with an 8.14% efficiency and 0F shows the lowest efficiency of 1.28%. Moreover, the planar-type perovskite solar cell (PSC) prepared with 2F as a dopant-free hole transport material shows a high power conversion efficiency of 14.5% due to its high charge transporting properties, which were significantly improved compared with the corresponding PSC device obtained from 0F (8.5%). From the studies, it is demonstrated that low variation in the local dipole moment and the narrow distribution of 2F conformers make intermolecular interactions favorable, which may effectively drive crystal formations in the solid state and thus, higher charge transport properties compared with 1F and 3F.