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Hypoxic injury to the developing brain increases the risk of permanent behavioral deficits, but the precise mechanisms of hypoxic injury to the developing nervous system are poorly understood. In this study, we characterized the effects of developmental hypoxia (1% pO2 from 24 to 48 h post-fertilization, hpf) on diencephalic dopaminergic (DA) neurons in larval zebrafish and the consequences on the development of swimming behavior. Hypoxia reduced the number of diencephalic DA neurons at 48 hpf. Returning zebrafish larvae to normoxia after the hypoxia (i.e., hypoxia-recovery, HR) induced reactive oxygen species (ROS) accumulation. Real-time qPCR results showed that HR caused upregulation of proapoptotic genes, including p53 and caspase3, suggesting the potential for ROS-induced cell death. With HR, we also found an increase in TUNEL-positive DA neurons, a persistent reduction in the number of diencephalic DA neurons, and disrupted swimming development and behavior. Interestingly, post-hypoxia (HR) with the antioxidant N-acetylcysteine partially restored the number of DA neurons and spontaneous swimming behavior, demonstrating potential recovery from hypoxic injury. The present study provides new insights for understanding the mechanisms responsible for motor disability due to developmental hypoxic injury.

In article number 2002606, Seung Goo Lee, Kilwon Cho, and co‐workers demonstrate a finger padinspired multimodal mechanoelectric sensor for material discrimination and texture recognition. By integrating various electrical working mechanisms of piezoelectric, triboelectric, and piezoresistive, the sensor can identify and distinguish the external stresses from a single stimulus to a combination of multiple stimuli, enabling a potential application of artificial sensory systems for biomimetic prosthesis and robotic skins. [Image: see text]

In article number 2001184, Seung Goo Lee, Kilwon Cho, and co‐workers demonstrate a user‐interactive thermotherapeutic electronic skin by integrating thermochromic composite and a stretchable strain sensor. Both heat and color of the device are easily controlled by external mechanical strain. This device exhibits a potential application in effective connective tissue injury rehabilitation, while avoiding skin burns. [Image: see text]

A sweat sensor is expected to be the most appropriate wearable device for noninvasive healthcare monitoring. However, the practical use of sweat sensors is impeded by irregular and low sweat secretion rates. Here, a sweat-collecting patch that can collect sweat efficiently for fast and continuous healthcare monitoring is demonstrated. The patch uses cactus-spine-inspired wedge-shaped wettability-patterned channels on a hierarchical microstructured/nanostructured surface. The channel shape, in combination with the superhydrophobic/superhydrophilic surface materials, induces a unidirectional Laplace pressure that transports the sweat to the sensing area spontaneously even when the patch is aligned vertically. The patch demonstrates superior sweat-collecting efficiency and reduces the time required to fill the sensing area by transporting sweat almost without leaving it inside the channel. Therefore, a sensor based on the patch responds quickly to biochemicals in sweat, and the patch enables the continuous monitoring of changes in sweat biochemicals according to their changes in the wearer's blood.

User‐interactive electronic skin (e‐skin) with a distinguishable output has enormous potential for human–machine interfaces and healthcare applications. Despite advances in user‐interactive e‐skins, advances in visual user‐interactive therapeutic e‐skins remain rare. Here, a user‐interactive thermotherapeutic device is reported that is fabricated by combining thermochromic composites and stretchable strain sensors consisting of strain‐responsive silver nanowire networks on surface energy‐patterned microwrinkles. Both the color and heat of the device are easily controlled through electrical resistance variation induced by applied mechanical strain. The resulting monolithic device exhibits substantial changes in optical reflectance and temperature with durability, rapid response, high stretchability, and linear sensitivity. The approach enables a low‐expertise route to fabricating dynamic interactive thermotherapeutic e‐skins that can be used to effectively rehabilitate injured connective tissues as well as to prevent skin burns by simultaneously accommodating stretching, providing heat, and exhibiting a color change., User‐interactive thermotherapeutic electronic skin (e‐skin) is fabricated by combining thermochromic composites and stretchable strain sensors consisting of strain‐responsive silver nanowire networks on surface energy‐patterned microwrinkles. Both the color and heat of the device are easily controlled through electrical resistance variation induced by external mechanical strain. This e‐skin can be applied to effectively rehabilitate a connective tissue injury, being avoided from skin burns.

The developing nervous system depends upon precise regulation of oxygen levels. Hypoxia, the condition of low oxygen concentration, can interrupt developmental sequences and cause a range of molecular, cellular and neuronal changes and injuries. The roles and effects of hypoxia on the central nervous system (CNS) are poorly characterized, even though hypoxia is simultaneously a normal component of development, a potentially abnormal environmental stressor in some settings, and a clinically important complication, for example of prematurity. Work over the past decade has revealed that hypoxia causes specific disruptions in the development of CNS connectivity, altering axon pathfinding and synapse development. The goals of this article are to review hypoxia's effects on the development of CNS connectivity, including its genetic and molecular mediators, and the changes it causes in CNS circuitry and function due to regulated as well as unintended mechanisms. The transcription factor HIF1α is the central mediator of the CNS response to hypoxia (as it is elsewhere in the body), but hypoxia also causes a dysregulation of gene expression. Animals appear to have evolved genetic and molecular responses to hypoxia that result in functional behavioral alterations to adapt to the changes in oxygen concentration during CNS development. Understanding the molecular pathways underlying both the normal and abnormal effects of hypoxia on CNS connectivity may reveal novel insights into common neurodevelopmental disorders. In addition, this Review explores the current gaps in knowledge, and suggests important areas for future studies., Summary: The nervous system's exposure to hypoxia has developmental and clinical relevance. In this Review, the authors discuss the effects of hypoxia on the development of the CNS, and its long-term behavioral and neurodevelopmental consequences.

Hypoxic injury to the developing human brain is a complication of premature birth and is associated with long-term impairments of motor function. Disruptions of axon and synaptic connectivity have been linked to developmental hypoxia, but the fundamental mechanisms impacting motor function from altered connectivity are poorly understood. We investigated the effects of hypoxia on locomotor development in zebrafish. We found that developmental hypoxia resulted in decreased spontaneous swimming behavior in larva, and that this motor impairment persisted into adulthood. In evaluation of the diencephalic dopaminergic neurons, which regulate early development of locomotion and constitute an evolutionarily conserved component of the vertebrate dopaminergic system, hypoxia caused a decrease in the number of synapses from the descending dopaminergic diencephalospinal tract (DDT) to spinal cord motor neurons. Moreover, dopamine signaling from the DDT was coupled jointly to motor neuron synaptogenesis and to locomotor development. Together, these results demonstrate the developmental processes regulating early locomotor development and a requirement for dopaminergic projections and motor neuron synaptogenesis. Our findings suggest new insights for understanding the mechanisms leading to motor disability from hypoxic injury of prematurity.

이 연구는 ``이주와 교육``을 개념적으로 연계하는 조망방석으로 한국인의 삶의 형태를 묘사하고 설명해 보고자 하는 문제의식에서 출발한다. 이 연구의 목적은 ``이주`` 와 ``교육``사이의 상호 연관된 중앙주의 문화에 대해 개념화하고, 그러한 중앙주의 문화가 교육이주의 형태로 반영되는 과정을 대구 수성구의 사례를 통해 실증적으로 분석하고자 한다. 여기서 연구자가 제시하는 ``중앙주의`` 는 ``중앙지향``의 삶의 태도이고 문화적 패턴이다. 중앙주의는 지방 폄하와 중앙 숭배의 문화를 낳고, 특정지역의 정치경체적 자원의 독점을 낳는. 이러한 중앙주의 문화에서 교육이주는 무관심하게 넘길 수 없는 사회적 문제로 나타나고 있다. 특히 이 논문에서 다루는 대구 수성구는 이른바 ``교육특구`` 로서, 수도권을 중심으로 한 중앙지향의 중간 기착지 가능을 하고 있다. 중앙지향의 교육이주에 대한 실증적 분석의 결과에 따르면, 수성구 지역 학생들이 비수상구 지역 학생들보다 서울소재 대학으로 진학하는 경향이 더 큰 것으로 확인되었다. 즉, 대학수학능력시험 성적이 높은 학생들이 그렇지 않은 학생들보다 서울소재 대학으로 진학하는 교육이주의 경향이 뚜렷하게 나타난다는 것이다. 이러한 중앙지향 교육이주 현상은 다양한 대내외적 환경에 의해 작동된다.

Tools for genetically-determined visualization of synaptic circuits and interactions are necessary to build connectomics of the vertebrate brain and to screen synaptic properties in neurological disease models. Here we develop a transgenic FingR (fibronectin intrabodies generated by mRNA display) technology for monitoring synapses in live zebrafish. We demonstrate FingR labeling of defined excitatory and inhibitory synapses and show FingR applicability for dissecting synapse dynamics in normal and disease states. Using our system we show that chronic hypoxia, associated with neurological defects in preterm birth, affects dopaminergic neuron synapse number depending on the developmental timing of hypoxia.

Abused amphetamines, such as d-amphetamine (AMPH) and methamphetamine (METH), are highly addictive and destructive to health and productive lifestyles. The abuse of these drugs is associated with impulsive behavior, which is likely to contribute to addiction. The amphetamines also differentially damage dopamine (DA) and serotonin (5-HT) systems, which regulate impulsive behavior; therefore, exposure to these drugs may differentially alter impulsive behavior to effect the progression of addiction. We examined the impact of neurotoxicity induced by three amphetamines on impulsive action using a stop-signal task in rats. Animals were rewarded with a food pellet after lever pressing (i.e., a go trial), unless an auditory cue was presented and withholding lever press gained reward (i.e., a stop trial). Animals were trained on the task and then exposed to a neurotoxic regimen of either AMPH, p-chloroamphetamine (PCA), or METH. These regimens preferentially reduced DA transporter levels in striatum, 5-HT transporter levels in prefrontal cortex, or both, respectively. Assessment of performance on the stop-signal task beginning 1 week after the treatment revealed that AMPH produced a deficit in go-trial performance, whereas PCA did not alter performance on either trial type. In contrast, METH produced a deficit in stop-trial performance (i.e., impulsive action) but not go-trial performance. These findings suggest that the different neurotoxic consequences of substituted amphetamines are associated with different effects on inhibitory control over behavior. Thus, the course of addiction and maladaptive behavior resulting from exposure to these substances is likely to differ.

Electrostatic interactions between polymers and metal ions at the air-water interface and in resulting LB films were investigated. The polymer was prepared from radical copolymerization of 2-(perfluorooctyl)ethyl monomaleate with triethyleneglycol methyl vinyl ether. The metal ions examined were Na+, Cs+, Mg2+, Fe2+, Al3+, and Fe3+. The surface pressure-area isotherms show that all the monolayers on aqueous metal ions reveal more expanded phases than that on pure water. From the FT-IR (reflection and transmission) spectra, the formation of carboxylate salts and the relative pendent orientation of the polymer in LB film could be estimated. Quantitative analysis of metal ion concentration incorporated into the LB film was carried out by XPS measurement.

Monooctadecyl maleate and monooctadecyl itaconate copolymers containing pendent oligoethers and carboxyls were synthesized and spread on pure water, on the aqueous poly(allylamine), and on saturated aqueous NaC1. Examination of the monolayer properties of the polymers by surface pressure-area isotherms reveals that their pendent oligoethers lie at the air-water interface at low surface pressures and are forced down into the subphase when the film is compressed. This orientation switching by compression-expansion cycle of monolayers is reproducible. Another pendant of carboxyls makes these polymers possible to form the polyion-complexed monolayers with the subphase polymer poly(allylamine) at the air-water interface. The polyion-complexation at the air-water interface and in resulting Langmuir-Blodgett film was confirmed by the surface pressure-area isotherm and FT-IR spectroscopy, respectively. SEM observation of these films on a porous membrane filter showed that the six-layer film was sufficien...

Methamphetamine (METH) induces neurotoxic changes, including partial striatal dopamine depletions, which are thought to contribute to cognitive dysfunction in rodents and humans. The dorsal striatum is implicated in action–outcome (A–O) and stimulus–response (S–R) associations underlying instrumental learning. Thus, the present study examined the long-term consequences of METH-induced neurotoxicity on A–O and S–R associations underlying appetitive instrumental behavior. Rats were pretreated with saline or a neurotoxic regimen of METH (4 × 7.5–10 mg/kg). Rats trained on random ratio (RR) or random interval (RI) schedules of reinforcement were then subjected to outcome devaluation or contingency degradation, followed by an extinction test. All rats then were killed, and brains removed for determination of striatal dopamine loss. The results show that: (1) METH pretreatment induced a partial 45–50% decrease in striatal dopamine tissue content in dorsomedial and dorsolateral striatum; (2) METH-induced neurotoxicity did not alter acquisition of instrumental behavior on either RR or RI schedules; (3) outcome devaluation and contingency degradation similarly decreased responding in saline- and METH-pretreated rats trained on the RR schedule, suggesting intact A–O associations guiding behavior; (4) outcome devaluation after training on the RI schedule decreased extinction responding only in METH-pretreated rats, suggesting impaired S–R associations. Overall, these data suggest that METH-induced neurotoxicity, possibly due to impairment of the function of dorsolateral striatal circuitry, may decrease cognitive flexibility by impairing the ability to automatize behavioral patterns.

Nicotine, the psychoactive ingredient in tobacco, can be neuroprotective but the mechanism is unknown. In the adult hippocampus, chronic nicotine can increase expression of growth factors which could contribute to nicotine's neuroprotective effects. During development, nicotine could also increase expression of neurotrophic factors. Therefore, we determined whether chronic neonatal nicotine (CNN) exposure increased mRNA expression levels of brain-derived neurotrophic factor (BDNF), nerve-growth factor (NGF), neurotrophin-3 (NT-3), fibroblast growth factor-2 (FGF-2), and insulin-like growth factor-1 (IGF-1). Nicotine (6 mg/kg/day in milk formula) or milk formula (controls) were delivered in three daily doses via oral gastric intubation to rat pups from postnatal day (P)1 to P8, and then sacrificed. Brains were processed for in situ hybridization using specific (35)S-labeled cRNA probes. At P8, CNN had a significant stimulant treatment effect on the expression of BDNF, FGF-2, NT-3 and IGF-1 [p

Hippocampal inhibitory interneurons are a diverse population of cells widely scattered in the hippocampus, where they regulate hippocampal circuit activity. The hippocampus receives cholinergic projections from the basal forebrain, and functional studies have suggested the presence of different subtypes of nicotinic acetylcholine receptors (AChRs) on gamma-aminobutyric acid (GABA)ergic interneurons. Single-cell polymerase chain reaction analysis had confirmed that several nAChR subunit mRNAs are co-expressed with glutamate decarboxylase 67 (GAD67), the marker for GABAergic interneurons. In this anatomical study, we systematically investigated the co-expression of GAD67 with different nAChR subunits by using double in situ hybridization with a digoxigenin-labeled GAD67 probe and (35)S-labeled probes for nAChR subunits (alpha2, alpha3, alpha4, alpha5, alpha6, alpha7, beta2, beta3, and beta4). The results revealed that most GAD67-positive interneurons expressed beta2, and 67 % also expressed alpha7 mRNA. In contrast, mRNA expression of other subunits was limited; only 13 % of GAD67-positive neurons co-expressed alpha4, and less than 10% expressed transcripts for alpha2, alpha3, alpha5, or beta4. Most GAD67/alpha2 co-expression was located in CA1/CA3 stratum oriens, and GAD67/alpha5 co-expression was predominantly detected in CA1/CA3 stratum radiatum/lacunosum moleculare and the dentate gyrus. Expression of alpha6 and beta3 mRNAs was rarely detected in the hippocampus, and mRNAs were not co-expressed with GAD67. These findings suggest that the majority of nicotinic responses in GABAergic interneurons should be mediated by a homomeric alpha7 or heteromeric alpha7*-containing nAChRs. Other possible combinations such as alpha2beta2*, alpha4beta2*, or alpha5beta2* heteromeric nAChRs could contribute to functional nicotinic response in subsets of GABAergic interneurons but overall would have a minor role.

This study addressed the question of whether radioactive hybridization signal intensities are reduced in combined isotopic and non-isotopic double in situ hybridization (DISH) compared with those in single in situ hybridization (ISH). Non-isotopic digoxigenin (Dig)-labeled hybrids were detected using an alkaline phosphatase (AP) enzymatic reaction which results in nitroblue tetrazolium chloride (NBT)/5-bromo-4-chloro-3-indolyl phosphate (BCIP)-salt precipitation that could shield S35-radiation from penetrating to the surface. Sections were plastic coated of with 2% parlodion to prevent a chemical reaction between AP and developer during processing of the photosensitive emulsion, which could further reduce radioactive hybridization signal detection by autoradiography. We used DISH with a hybridization cocktail of radioactive S35- and Dig-labeled GAD67 cRNA probes. In order to avoid competition for the same complementary sequence, the probes were directed towards different sequences of the glutamic acid decarboxylase (GAD67) mRNA, resulting in co-detection of isotopic and non-isotopic hybrids in close to 100% of GAD67 positive cells. Quantitation of autoradiograms showed that there was no reduction of autoradiographic signal intensity from S35-labeled hybrids in the presence of Dig-labeled hybrids. Plastic coating of single or dual hybridized sections did not reduce the radioactive signal intensity. When mRNAs for nicotinic acetylcholine receptor (nAChR) subunits were detected with subunit specific S35-labeled cRNA probes in GAD67 hippocampal interneurons the total numbers of nAChR subunit expressing cells remained the same in single or double hybridized sections even for low abundant mRNAs. Together, these results indicate that combined radioactive and non-radioactive DISH does not interfere with the detection of the radiation signal from the S35-labeled hybrids, and neither specificity nor sensitivity is compromised.

In the enteric nervous system (ENS) excitatory nicotinic cholinergic transmission is mediated by neuronal nicotinic acetylcholine receptors (nAChR) and is critical for the regulation of gastric motility. nAChRs are ligand-gated pentameric ion channels found in the CNS and peripheral nervous system. The expression of heteromeric nAChR and receptor subunit mRNAs was investigated in the neonatal rat ENS using receptor autoradiography with the radiolabeled ligand (125)I-epibatidine, and in situ hybridization with subtype specific probes for ligand binding alpha (alpha2, alpha3, alpha4, alpha5, alpha6) and structural beta (beta2, beta3, beta4) subunits. The results showed strong nicotine sensitive binding of (125)I-epibatidine around the stomach, and small and large intestines. The binding was partially displaced by A85380, a nicotinic ligand which differentiates between different heteromeric nAChR subtypes, suggesting a mixed receptor population. Radioactive in situ hybridization detected expression of alpha3, alpha5, alpha7, beta2 and beta4 mRNA in the myenteric plexus of the stomach, and small and large intestines. In the submucosal plexus of the small and large intestines expression of alpha3, alpha5 and beta4 was found in some ganglia. There was no signal for alpha4, alpha6 and beta3 in the ENS but positive hybridization signal for alpha2 transcripts was seen in some areas of the small intestines. However, the signal was not associated with any ganglion cells. The results confirm the presence of heteromeric nAChRs in the ENS similar to those found in the peripheral nervous system, with the majority being composed of alpha3(alpha5)beta4, and a few alpha3beta2 nAChRs. In addition, homomeric alpha7 nAChRs could be present.

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated cation channels composed of alpha and beta subunits. nAChR subunit expression is highly regulated during development. Previous studies have revealed increased expression of alpha3, alpha5, alpha7, and beta4 subunit mRNAs and alpha7 binding sites during hippocampal and cortical development. Here, we examined the expression of alpha2 subunit mRNA in rat cortex and hippocampus using highly sensitive radioactive in situ hybridization. alpha2 Subunit mRNA expression was first detected at P3 in cortex and hippocampus. During postnatal development the distribution of alpha2 subunit mRNA expression was spatially similar to the one found in adult, exhibiting highly restricted expression in scattered cells mostly in cortical layer V and retrosplenial cortex, and in scattered cells in CA1/CA3 stratum oriens and CA3 stratum radiatum. However, the expression intensity and number of alpha2 positive cells strongly increased to reach peak levels in both cortex and hippocampus at P7 and decreased thereafter to moderate to low to levels. Double in situ hybridization revealed that most, but not all, alpha2 mRNA expression was located in non-pyramidal GAD-positive cortical and hippocampal interneurons. Thus, similar to other nAChR subunits, alpha2 mRNA expression is transiently upregulated during postnatal development and nAChRs containing alpha2 subunits could regulate GABAergic activity during a critical period of network formation.

Interactions between polymers and metal ions at the air-water interface and in resulting LB films were investigated. The polymer was prepared from radical copolymerization of n-octadecyl monomaleate with a vinyl ether comonomer. The metal ions examined were Na+, Cs+, Mg2+, Fe2+, Al3+, and Fe3+. The surface pressure-area isotherms show that all the monolayers on aqueous metal ion reveal more expanded phases than on pure water. From the FT-IR (reflection and transmission) spectra, the formation of pendent carboxylate salts and the relative orientation of the polymer in LB film could be estimated. Quantitative analysis of metal ion concentration incorporated into the LB film was carried out by XPS measurement.

Background Despite the fundamental biological importance and clinical relevance of characterizing the effects of chronic hypoxia exposure on central nervous system (CNS) development, the changes in gene expression from hypoxia are unknown. It is not known if there are unifying principles, properties, or logic in the response of the developing CNS to hypoxic exposure. Here, we use the small vertebrate zebrafish (Danio rerio) to study the effects of hypoxia on connectivity gene expression across development. We perform transcriptional profiling at high temporal resolution to systematically determine and then experimentally validate the response of CNS connectivity genes to hypoxia exposure. Results We characterized mRNA changes during development, comparing the effects of chronic hypoxia exposure at different time-points. We focused on changes in expression levels of a subset of 1270 genes selected for their roles in development of CNS connectivity, including axon pathfinding and synapse formation. We found that the majority of CNS connectivity genes were unaffected by hypoxia. However, for a small subset of genes hypoxia significantly affected their gene expression profiles. In particular, hypoxia appeared to affect both the timing and levels of expression, including altering expression of interacting gene pairs in a fashion that would potentially disrupt normal function. Conclusions Overall, our study identifies the response of CNS connectivity genes to hypoxia exposure during development. While for most genes hypoxia did not significantly affect expression, for a subset of genes hypoxia changed both levels and timing of expression. Importantly, we identified that some genes with interacting proteins, for example receptor/ligand pairs, had dissimilar responses to hypoxia that would be expected to interfere with their function. The observed dysynchrony of gene expression could impair the development of normal CNS connectivity maps. Electronic supplementary material The online version of this article (doi:10.1186/s12864-016-2638-x) contains supplementary material, which is available to authorized users.