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The specification of the embryonic central nervous system (CNS) into future brain (forebrain, midbrain, or hindbrain) and spinal cord (SC) regions is a critical step of CNS development. A previous chicken embryo study indicated that anterior epiblast cells marked by Sox2 N2 enhancer activity are specified to the respective brain regions during the transition phase of the epiblast to the neural plate-forming neural primordium. The present study showed that the SC precursors positioned posterior to the hindbrain precursors in the anterior epiblast migrated posteriorly in contrast to the anterior migration of brain precursors. The anteroposterior specification of the CNS precursors occurs at an analogous time (∼E7.5) in mouse embryos, in which an anterior-to-posterior incremental gradient of Wnt signal strength was observed. To examine the possible Wnt signal contribution to the anteroposterior CNS primordium specification, we utilized mouse epiblast stem cell (EpiSC)-derived neurogenesis in culture. EpiSCs maintained in an activin- and FGF2-containing medium start neural development after the removal of activin, following a day in a transitory state. We placed activin-free EpiSCs in EGF- and FGF2-containing medium to arrest neural development and expand the cells into neural stem cells (NSCs). Simultaneously, a Wnt antagonist or agonist was added to the culture, with the anticipation that different levels of Wnt signals would act on the transitory cells to specify CNS regionality; then, the Wnt-treated cells were expanded as NSCs. Gene expression profiles of six NSC lines were analyzed using microarrays and single-cell RNA-seq. The NSC lines demonstrated anteroposterior regional specification in response to increasing Wnt signal input levels: forebrain-midbrain-, hindbrain-, cervical SC-, and thoracic SC-like lines. The regional coverage of these NSC lines had a range; for instance, the XN1 line expressed Otx2 and En2, indicating midbrain characteristics, but additionally expressed the SC-characteristic Hoxa5. The ranges in the anteroposterior specification of neural primordia may be narrowed as neural development proceeds. The thoracic SC is presumably the posterior limit of the contribution by anterior epiblast-derived neural progenitors, as the characteristics of more posterior SC regions were not displayed.

Functional magnetic resonance imaging (fMRI) in behaving monkeys has a strong potential to bridge the gap between human neuroimaging and primate neurophysiology. In monkey fMRI, to restrain head movements, researchers usually surgically implant a plastic head-post on the skull. Although time-proven to be effective, this technique could create burdens for animals, including a risk of infection and discomfort. Furthermore, the presence of extraneous objects on the skull, such as bone screws and dental cement, adversely affects signals near the cortical surface. These side effects are undesirable in terms of both the practical aspect of efficient data collection and the spirit of “refinement” from the 3R's. Here, we demonstrate that a completely non-invasive fMRI scan in awake monkeys is possible by using a plastic head mask made to fit the skull of individual animals. In all of the three monkeys tested, longitudinal, quantitative assessment of head movements showed that the plastic mask has effectively suppressed head movements, and we were able to obtain reliable retinotopic BOLD signals in a standard retinotopic mapping task. The present, easy-to-make plastic mask has a strong potential to simplify fMRI experiments in awake monkeys, while giving data that is as good as or even better quality than that obtained with the conventional head-post method.

Abstract Animals can expect rewards under equivocal situations. The lateral hypothalamus (LH) is thought to process motivational information by producing valence signals of reward and punishment. Despite rich studies using rodents and non-human primates, these signals have been assessed separately in appetitive and aversive contexts; therefore, it remains unclear what information the LH encodes in equivocal situations. To address this issue, macaque monkeys were conditioned under a bivalent context in which reward and punishment were probabilistically delivered, in addition to appetitive and aversive contexts. The monkeys increased approaching behavior similarly in the bivalent and appetitive contexts as the reward probability increased. They increased avoiding behavior under the bivalent and aversive contexts as the punishment probability increased, but the mean frequency was lower under the bivalent context than under the aversive context. The population activity correlated with these mean behaviors. Moreover, the LH produced fine prediction signals of reward expectation, uncertainty, and predictability consistently in the bivalent and appetitive contexts by recruiting context-independent and context-dependent subpopulations of neurons, while it less produced punishment signals in the aversive and bivalent contexts. Further, neural ensembles encoded context information and “rewarding-unrewarding” and “reward-punishment” valence. These signals may motivate individuals robustly in equivocal environments.

Uterine leiomyosarcoma (ULMS) is a malignant stromal tumor arising from the myometrium with a poor prognosis and very limited response to current chemotherapy. This study aimed to identify novel targets for ULMS through a three-step screening process using a chemical library consisting of 1271 Food and Drug Administration-approved drugs. First, we evaluated their inhibitory effects on ULMS cells and identified four candidates: proscillaridin A, lanatoside C, floxuridine, and digoxin. Then, we subcutaneously or orthotopically transplanted SK-UT-1 cells into mice to establish mouse models. In vivo analyses showed that proscillaridin A and lanatoside C exerted a superior antitumor effect. The results of mRNA sequencing showed that uncoupling protein 2 (UCP2) was suppressed in the sirtuin signaling pathway, increasing reactive oxygen species (ROS) and inducing cell death. Moreover, the downregulation of UCP2 induced ROS and suppressed ULMS cell growth. Furthermore, analyses using clinical samples showed that UCP2 expression was significantly upregulated in ULMS tissues than in myoma tissues both at the RNA and protein levels. These findings suggested that UCP2 is a potential therapeutic target and can contribute to the development of novel therapeutic strategies in patients with ULMS.

Abstract Low-temperature plasma is being widely used in the various fields of life science, such as medicine and agriculture. Plasma-activated solutions have been proposed as potential cancer therapeutic reagents. We previously reported that plasma-activated Ringer’s lactate solution exhibited selective cancer-killing effects, and that the plasma-treated L-sodium lactate in the solution was an anti-tumor factor; however, the components that are generated through the interactions between plasma and L-sodium lactate and the components responsible for the selective killing of cancer cells remain unidentified. In this study, we quantified several major chemical products, such as pyruvate, formate, and acetate, in plasma-activated L-sodium lactate solution by nuclear magnetic resonance analysis. We further identified novel chemical products, such as glyoxylate and 2,3-dimethyltartrate, in the solution by direct infusion-electrospray ionization with tandem mass spectrometry analysis. We found that 2,3-dimethyltartrate exhibited cytotoxic effects in glioblastoma cells, but not in normal astrocytes. These findings shed light on the identities of the components that are responsible for the selective cytotoxic effect of plasma-activated solutions on cancer cells, and provide useful data for the potential development of cancer treatments using plasma-activated L-sodium lactate solution.

Abstract Background Children with autism spectrum disorder (ASD) may experience difficulty adapting to daily life in a preschool or school settings and are likely to develop psychosomatic symptoms. For a better understanding of the difficulties experienced daily by preschool children and adolescents with ASD, this study investigated differences in eye gaze behavior in the classroom environment between children with ASD and those with typical development (TD). Methods The study evaluated 30 children with ASD and 49 children with TD. Participants were presented with images of a human face and a classroom scene. While they gazed at specific regions of visual stimuli, eye tracking with an iView X system was used to evaluate and compare the duration of gaze time between the two groups. Results Compared with preschool children with TD, preschool children with ASD spent less time gazing at the eyes of the human face and the object at which the teacher pointed in the classroom image. Preschool children with TD who had no classroom experience tended to look at the object the teacher pointed at in the classroom image. Conclusion Children with ASD did not look at the human eyes in the facial image or the object pointed at in the classroom image, which may indicate their inability to analyze situations, understand instruction in a classroom, or act appropriately in a group. This suggests that this gaze behavior of children with ASD causes social maladaptation and psychosomatic symptoms. A therapeutic approach that focuses on joint attention is desirable for improving the ability of children with ASD to adapt to their social environment.

ISO standards exist for evaluating sunscreens, such as those based on visual inspection. This assessment yields subjective results and is thus unreliable. Therefore, to verify the results of the visual assessment of sunscreens, quantitative evaluation methods are necessary. These methods require the measurement of the total radiation energy that is diffusely transmitted in all directions. For the measurements, although an integrating sphere is widely used to measure diffusely transmitted radiation, a simpler measurement would contribute to the easy usage of quantitative and objective evaluation. We propose the use of fluorescent materials as an alternative method to characterize sunscreens. In this method, a layer containing a fluorescent material is placed behind the sunscreen, and when the excitation radiation transmitted through the sunscreen reaches the fluorescent layer, it emits fluorescence. The feasibility of this measurement method was evaluated through numerical analysis and it demonstrated that hemispheric transmittance can be measured when the fluorescent layer is of high concentration or thick. Additionally, a prototype fluorescent layer was fabricated, and also the results were compared with the amount of diffusely transmitted UV from several commercial sunscreens. This pilot evaluation measurement method showed that the UV shielding index shown on the package does not necessarily truly reflect the amount of UV energy transmitted through the sunscreen, thus failing to provide the expected protection.

Non-thermal plasma (NTP), an engineered technology to generate reactive species, induces ferroptosis and/or apoptosis specifically in various-type cancer cells. NTP-activated Ringer's lactate (PAL) is another modality for cancer therapy at preclinical stage. Here we found that PAL induces selective ferroptosis of malignant mesothelioma (MM) cells, where non-targeted metabolome screening identified upregulated citrulline-nitric oxide (.NO) cycle as a PAL target. .NO probe detected biphasic peaks transiently at PAL exposure with time-dependent increase, which was responsible for inducible . NO synthase (iNOS) overexpression through NF-κB activation. .NO and lipid peroxidation occupied lysosomes as a major compartment with increased TFEB expression. Not only ferrostatin-1 but inhibitors for . NO and/or iNOS could suppress this ferroptosis. PAL-induced ferroptosis accompanied autophagic process in the early phase, as demonstrated by an increase in essential amino acids, LC3B-II, p62 and LAMP1, transforming into the later phase with boosted lipid peroxidation. Therefore, .NO-mediated lysosomal impairment is central in PAL-induced ferroptosis.

Abstract Non-thermal atmospheric pressure plasma has been proposed as a new therapeutic tool for cancer treatment. Recently, plasma-activated medium (PAM) has been widely studied in various cancer types. However, there are only few reports demonstrating the anti-tumour effects of PAM in an animal model reflecting pathological conditions and the accompanying mechanism. Here we investigated the inhibitory effect of PAM on the metastasis of ovarian cancer ES2 cells in vitro and in vivo. We demonstrated that ES2 cell migration, invasion and adhesion were suppressed by PAM at a certain PAM dilution ratio, whereas cell viability remained unaffected. In an in vivo mouse model of intraperitoneal metastasis, PAM inhibited peritoneal dissemination of ES2 cells, resulting in prolonged survival. Moreover, we assessed the molecular mechanism and found that MMP-9 was decreased by PAM. On further investigation, we also found that PAM prevented the activation of the MAPK pathway by inhibiting the phosphorylation of JNK1/2 and p38 MAPK. These findings indicate that PAM inhibits the metastasis of ovarian cancer cells through reduction of MMP-9 secretion, which is critical for cancer cell motility. Our findings suggest that PAM intraperitoneal therapy may be a promising treatment option for ovarian cancer.

Background Exposure to chronic psychosocial stress is a risk factor for atherosclerosis‐based cardiovascular disease. We previously demonstrated the increased expressions of cathepsin S (CatS) in atherosclerotic lesions. Whether CatS participates directly in stress‐related neointimal hyperplasia has been unknown. Methods and Results Male wild‐type and CatS‐deficient mice that underwent carotid ligation injury were subjected to chronic immobilization stress for morphological and biochemical studies at specific times. On day 14 after stress/surgery, stress enhanced the neointima formation. At the early time points, the stressed mice had increased plaque elastin disruption, cell proliferation, macrophage accumulation, mRNA and/or protein levels of vascular cell adhesion molecule‐1, angiotensin II type 1 receptor, monocyte chemoattractant protein‐1, gp91phox, stromal cell–derived factor‐1, C‐X‐C chemokine receptor‐4, toll‐like receptor‐2, toll‐like receptor‐4, SC35, galectin‐3, and CatS as well as targeted intracellular proliferating‐related molecules (mammalian target of rapamycin, phosphorylated protein kinase B, and p‐glycogen synthase kinase‐3α/β). Stress also increased the plaque matrix metalloproteinase‐9 and matrix metalloproteinase‐2 mRNA expressions and activities and aorta‐derived smooth muscle cell migration and proliferation. The genetic or pharmacological inhibition of CatS by its specific inhibitor (Z‐FL‐COCHO) ameliorated the stressed arterial targeted molecular and morphological changes and stressed aorta‐derived smooth muscle cell migration. Both the genetic and pharmacological interventions had no effect on increased blood pressure in stressed mice. Conclusions These results demonstrate an essential role of CatS in chronic stress–related neointimal hyperplasia in response to injury, possibly via the reduction of toll‐like receptor‐2/toll‐like receptor‐4–mediated inflammation, immune action, and smooth muscle cell proliferation, suggesting that CatS will be a novel therapeutic target for stress‐related atherosclerosis‐based cardiovascular disease.

Cortico-basal ganglia circuits are critical regulators of reward-based decision making. Reinforcement learning models posit that action reward value is encoded by the firing activity of striatal medium spiny neurons (MSNs) and updated upon changing reinforcement contingencies by dopamine (DA) signaling to these neurons. However, it remains unclear how the anatomically distinct direct and indirect pathways through the basal ganglia are involved in updating action reward value under changing contingencies. MSNs of the direct pathway predominantly express DA D1 receptors and those of the indirect pathway predominantly D2 receptors, so we tested for distinct functions in behavioral adaptation by injecting D1 and D2 receptor antagonists into the putamen of two macaque monkeys performing a free choice task for probabilistic reward. In this task, monkeys turned a handle toward either a left or right target depending on an asymmetrically assigned probability of large reward. Reward probabilities of left and right targets changed after 30–150 trials, so the monkeys were required to learn the higher-value target choice based on action–outcome history. In the control condition, the monkeys showed stable selection of the higher-value target (that more likely to yield large reward) and kept choosing the higher-value target regardless of less frequent small reward outcomes. The monkeys also made flexible changes of selection away from the high-value target when two or three small reward outcomes occurred randomly in succession. DA D1 antagonist injection significantly increased the probability of the monkey switching to the alternate target in response to successive small reward outcomes. Conversely, D2 antagonist injection significantly decreased the switching probability. These results suggest distinct functions of D1 and D2 receptor-mediated signaling processes in action selection based on action–outcome history, with D1 receptor-mediated signaling promoting the stable choice of higher-value targets and D2 receptor-mediated signaling promoting a switch in action away from small reward outcomes. Therefore, direct and indirect pathways appear to have complementary functions in maintaining optimal goal-directed action selection and updating action value, which are dependent on D1 and D2 DA receptor signaling.

The striatum is an input channel of the basal ganglia and is well known to be involved in reward-based decision making and learning. At the macroscopic level, the striatum has been postulated to contain parallel functional modules, each of which includes neurons that perform similar computations to support selection of appropriate actions for different task contexts. At the single-neuron level, however, recent studies in monkeys and rodents have revealed heterogeneity in neuronal activity even within restricted modules of the striatum. Looking for generality in the complex striatal activity patterns, here we briefly survey several types of striatal activity, focusing on their usefulness for mediating behaviors. In particular, we focus on two types of behavioral tasks: reward-based tasks that use salient sensory cues and manipulate outcomes associated with the cues; and perceptual decision tasks that manipulate the quality of noisy sensory cues and associate all correct decisions with the same outcome. Guided by previous insights on the modular organization and general selection-related functions of the basal ganglia, we relate striatal activity patterns on these tasks to two types of computations: implementation of selection and evaluation. We suggest that a parsing with the selection/evaluation categories encourages a focus on the functional commonalities revealed by studies with different animal models and behavioral tasks, instead of a focus on aspects of striatal activity that may be specific to a particular task setting. We then highlight several questions in the selection-evaluation framework for future explorations.

Children with autism spectrum disorders (ASD) who have neurodevelopmental impairments in social communication often refuse to go to school because of difficulties in learning in class. The exact cause of maladaptation to school in such children is unknown. We hypothesized that these children have difficulty in paying attention to objects at which teachers are pointing. We performed gaze behavior analysis of children with ASD to understand their difficulties in the classroom. The subjects were 26 children with ASD (19 boys and 7 girls; mean age, 8.6 years) and 27 age-matched children with typical development (TD) (14 boys and 13 girls; mean age, 8.2 years). We measured eye movements of the children while they performed free viewing of two movies depicting actual classes: a Japanese class in which a teacher pointed at cartoon characters and an arithmetic class in which the teacher pointed at geometric figures. In the analysis, we defined the regions of interest (ROIs) as the teacher's face and finger, the cartoon characters and geometric figures at which the teacher pointed, and the classroom wall that contained no objects. We then compared total gaze time for each ROI between the children with ASD and TD by two-way ANOVA. Children with ASD spent less gaze time on the cartoon characters pointed at by the teacher; they spent more gaze time on the wall in both classroom scenes. We could differentiate children with ASD from those with TD almost perfectly by the proportion of total gaze time that children with ASD spent looking at the wall. These results suggest that children with ASD do not follow the teacher's instructions in class and persist in gazing at inappropriate visual areas such as walls. Thus, they may have difficulties in understanding content in class, leading to maladaptation to school.

PurposeNonequilibrium atmospheric pressure plasma (NEAPP) therapy has recently been focused on as a novel medical practice. Using cells with acquired paclitaxel/cisplatin resistance, we elucidated effects of indirect NEAPP-activated medium (NEAPP-AM) exposure on cell viability and tumor growth in vitro and in vivo.MethodsUsing chronic paclitaxel/cisplatin-resistant ovarian cancer cells, we applied indirect NEAPP-exposed medium to cells and xenografted tumors in a mouse model. Furthermore, we examined the role of reactive oxygen species (ROS) or their scavengers in the above-mentioned EOC cells.ResultsWe assessed the viability of NOS2 and NOS3 cells exposed to NEAPP-AM, which was prepared beforehand by irradiation with NEAPP for the indicated time. In NOS2 cells, viability decreased by approximately 30% after NEAPP-AM 120-sec treatment (PConclusionWe demonstrated that plasma-activated medium also had an anti-tumor effect on chemo-resistant cells in vitro and in vivo. Indirect plasma therapy is a promising treatment option for EOC and may contribute to a better patient prognosis in the future.

Dopamine, acetylcholine, and serotonin, the main modulators of the central nervous system, have been proposed to play important roles in the execution of movement, control of several forms of attentional behavior, and reinforcement learning. While the response pattern of midbrain dopaminergic neurons and its specific role in reinforcement learning have been revealed, the role of the other neuromodulators remains rather elusive. Here, we review our recent studies using extracellular recording from neurons in the pedunculopontine tegmental nucleus, where many cholinergic neurons exist, and the dorsal raphe nucleus, where many serotonergic neurons exist, while monkeys performed eye movement tasks to obtain different reward values. The firing patterns of these neurons are often tonic throughout the task period, while dopaminergic neurons exhibited a phasic activity pattern to the task event. The different modulation patterns, together with the activity of dopaminergic neurons, reveal dynamic information processing between these different neuromodulator systems.

Oxalate was synthesized in the glucose solution by irradiation with non-equilibrium atmospheric pressure plasma (NEAPP), in which the NEAPP plume contacted the solution surface, via the generation of several intermediate organic products such as gluconic acid. A thermodynamically unstable phase of calcium oxalate dihydrate crystallized rapidly during incubation of a NEAPP-irradiated glucose solution that contained calcium ions and was buffered at neutral pH. Longer irradiation times increased the growth rate and the number of seed crystals. [ABSTRACT FROM AUTHOR]

The lateral hypothalamus (LH), which plays a role in homeostatic functions such as appetite regulation, is also linked to arousal and motivational behavior. However, little is known about how these components are encoded in the LH. Thus cynomolgus monkeys were conditioned with two distinct contexts, i.e., an appetitive context with available rewards and an aversive context with predicted air puffs. Different LH neuron groups encoded different degrees of expectation, predictability, and risks of rewards in a specific manner. A nearly equal number of one-third of the recorded LH neurons showed a positive or negative correlation between their response to visual conditioned stimuli (CS) that predicted the probabilistic delivery of rewards (0%, 50%, and 100%) and the associative values. For another one-third of recorded neurons, a nearly equal number showed a positive or negative correlation between their responses to rewards [appetitive unconditioned stimulus (US)] and reward predictability. Some neurons exhibited their highest or lowest trace-period responses in the 50% reward trials. These response modulations were represented independently and overlaid on a consistent excitatory or inhibitory response across the conditioning events. LH neurons also showed consistent responses in the aversive context. However, the responses to aversive conditioning events depending on the air puff value and predictability were less common. The multifaceted modulation of consistent activity related to outcome predictions may reflect motivational and arousal signals. Furthermore, it may underlie the role the LH plays in the integration and relay of signals to cortices for adaptive and goal-directed physiological and behavioral responses to environmental changes. [ABSTRACT FROM AUTHOR]

Serotonin is known to play a key role in the regulation of emotional behavior. There have been conflicting hypotheses about whether the central serotonergic system is involved in positive or negative emotional information processing. To reveal whether and how such opposing information processing can be achieved by single neurons in the dorsal raphé nucleus (DRN), the major source of serotonin in the forebrain, we recorded the activity of DRN neurons while monkeys were conditioned in a Pavlovian procedure with two distinct contexts: an appetitive block where a reward was available; and an aversive one where an airpuff was delivered. We found that single DRN neurons were involved in several aspects of both appetitive and aversive information processing. First, more than half of the recorded DRN neurons discriminated between appetitive and aversive contexts by tonic changes in their activity. In the appetitive context, they then kept track of the expected reward value indicated by the conditioned stimuli. Some of them also encoded an error between the obtained and expected values. In the aversive context, the same neurons maintained tonic modulation in their activity throughout the block. However, modulation of their responses to aversive task events depending on airpuff probability was less common. Together, these results indicate that single DRN neurons encode both appetitive and aversive information, but over differing time scales: relatively shorter for appetitive, and longer for aversive. Such temporally distinct processes of value coding in the DRN may provide the neural basis of emotional information processing in different contexts. [ABSTRACT FROM AUTHOR]

Pharmacological experiments have shown that the modulation of brain serotonin levels has a strong impact on value-based decision making. Anatomical and physiological evidence also revealed that the dorsal raphé nucleus (DRN), a major source of serotonin, and the dopamine system receive common inputs from brain regions associated with appetitive and aversive information processing. The serotonin and dopamine systems also have reciprocal functional influences on each other. However, the specific mechanism by which serotonin affects value-based decision making is not clear. To understand the information carried by the DRN for reward-seeking behavior, we measured single neuron activity in the primate DRN during the performance of saccade tasks to obtain different amounts of a reward. We found that DRN neuronal activity was characterized by tonic modulation that was altered by the expected and received reward value. Consistent reward-dependent modulation across different task periods suggested that DRN activity kept track of the reward value throughout a trial. The DRN was also characterized by modulation of its activity in the opposite direction by different neuronal subgroups, one firing strongly for the prediction and receipt of large rewards, with the other firing strongly for small rewards. Conversely, putative dopamine neurons showed positive phasic responses to reward-indicating cues and the receipt of an unexpected reward amount, which supports the reward prediction error signal hypothesis of dopamine. I suggest that the tonic reward monitoring signal of the DRN, possibly together with its interaction with the dopamine system, reports a continuous level of motivation throughout the performance of a task. Such a signal may provide "reward context" information to the targets of DRN projections, where it may be integrated further with incoming motivationally salient information. [ABSTRACT FROM AUTHOR]

Expected reward impacts behavior and neuronal activity in brain areas involved in sensorimotor processes. However, where and how reward signals affect sensorimotor signals is unclear. Here, we show evidence that reward-dependent modulation of behavior depends on normal dopamine transmission in the striatum. Monkeys performed a visually guided saccade task in which expected reward gain was different depending on the position of the target. Saccadic reaction times were reliably shorter on large-reward trials than on small-reward trials. When position–reward contingency was switched, the reaction time difference changed rapidly. Injecting dopamine D1 antagonist into the caudate significantly attenuated the reward-dependent saccadic reaction time changes. Conversely, injecting D2 antagonist into the same region enhanced the reward-dependent changes. These results suggest that reward-dependent changes in saccadic eye movements depend partly on dopaminergic modulation of neuronal activity in the caudate nucleus. [ABSTRACT FROM AUTHOR]

Expectation of reward motivates our behaviors and influences our decisions. Indeed, neuronal activity in many brain areas is modulated by expected reward. However, it is still unclear where and how the reward-dependent modulation of neuronal activity occurs and how the reward-modulated signal is transformed into motor outputs. Recent studies suggest an important role of the basal ganglia. Sensorimotor/cognitive activities of neurons in the basal ganglia are strongly modulated by expected reward. Through their abundant outputs to the brain stem motor areas and the thalamocortical circuits, the basal ganglia appear capable of producing body movements based on expected reward. A good behavioral measure to test this hypothesis is saccadic eye movement because its brain stem mechanism has been extensively studied. Studies from our laboratory suggest that the basal ganglia play a key role in guiding the gaze to the location where reward is available. Neurons in the caudate nucleus and the substantia nigra pars reticulata are extremely sensitive to the positional difference in expected reward, which leads to a bias in excitability between the superior colliculi such that the saccade to the to-be-rewarded position occurs more quickly. It is suggested that the reward modulation occurs in the caudate where cortical inputs carrying spatial signals and dopaminergic inputs carrying reward-related signals are integrated. These data support a specific form of reinforcement learning theories, but also suggest further refinement of the theory. [ABSTRACT FROM AUTHOR]

A plasma-activated medium (PAM), which means a cell-culture medium irradiated with cold atmospheric plasmas or non-equilibrium atmospheric pressure plasma (NEAPP), has shown strong antitumor effects on various kinds of cells such as gastric cancer cells, human lung adenocarcinoma cells, human breast cancer cells and so on. In order to clarify the mechanism, it is extremely important to investigate the behaviors of stable and unstable reactive oxygen nitrogen species in culture medium irradiated by NEAPP. The roles of hydroxyl radicals (•OH) and nitric oxide (•NO) were studied to understand the dominant synthetic pathways of H2O2 and in culture medium irradiated with NEAPP. In the PAM, •OH in the aqueous phase was generated predominantly by photo-dissociation. However, most of the H2O2 nor generated in the PAM did not originate from aqueous •OH and •NO. Pathways for the generation of H2O2 and are suggested based on the high concentrations of intermediates generated at the gas/aqueous-phase interface following NEAPP irradiation. On the basis of these results, the reaction model of chemical species in the culture medium is proposed. [ABSTRACT FROM AUTHOR]

Octahedral particulates several tens of microns in size were synthesized in a culture medium irradiated through contact with a plume of non-equilibrium atmospheric-pressure plasma (NEAPP). The particulates were identified in the crystalline phase as calcium oxalate dihydrate (COD). The original medium contained constituents such as NaCl, d-glucose, CaCl2, and NaHCO3 but not oxalate or oxalic acid. The oxalate was clearly synthesized and crystallized in the medium as thermodynamically unstable COD crystals after the NEAPP irradiation. [ABSTRACT FROM AUTHOR]

Epithelial ovarian cancer (EOC) is the leading cause of cancer-related death in women in Western countries. Once patients experience recurrence, complete cure is almost impossible. Nonequilibrium atmospheric pressure plasma (NEAPP) therapy has recently been focused on as a novel medical practice. We have elucidated the effect of nonequilibrium atmospheric pressure plasma on the growth of EOC, particularly in plasma-activated medium (PAM). In our recent report, we examined the role of reactive oxygen species (ROS) or their scavengers in chronic antineoplastic-resistant EOC cells. As a result, PAM exerted the antitumor effect of EOC cells in vitro and in vivo, even in chemoresistant cells. There are several problems under investigation, including intracellular mechanism of antitumor effect by PAM and adverse event in vivo. Through recent results about plasma in cancer treatment, PAM therapy is a promising treatment option for EOC and may contribute to a better patient prognosis in the future. [ABSTRACT FROM AUTHOR]

Non-equilibrium atmospheric pressure plasmas generate a high electron density (on the order of 1016 electrons per cm-3) using Ar gas. Culture medium in air at room temperature was plasma-irradiated for several hundred seconds. Tens of micromolar hydrogen peroxide (H2O2) and millimolar levels of nitrous ion (NO2-) were detected in the plasma-irradiated culture medium (plasma activated medium; PAM) and selectively induced the apoptotic death of glioblastoma tumor cells, but did not kill normal mammary epithelial cells. A similar antitumor effect was induced by spiking the medium with comparable concentrations of H2O2 and NO2-. The PAM remained still a somewhat difference that it should also be assessed for understanding other latent mechanisms. [ABSTRACT FROM AUTHOR]