Prefrontal brain areas are implicated in the control of fear behavior. However, how prefrontal circuits control fear response to innate threat is poorly understood. Here, we show that the anterior ...cingulate cortex (ACC) and its input to the basolateral nucleus of amygdala (BLA) contribute to innate fear response to a predator odor in mice. Optogenetic inactivation of the ACC enhances freezing response to fox urine without affecting conditioned freezing. Conversely, ACC stimulation robustly inhibits both innate and conditioned freezing. Circuit tracing and slice patch recordings demonstrate a monosynaptic glutamatergic connectivity of ACC-BLA but no or very sparse ACC input to the central amygdala. Finally, our optogenetic manipulations of the ACC-BLA projection suggest its inhibitory control of innate freezing response to predator odors. Together, our results reveal the role of the ACC and its projection to BLA in innate fear response to olfactory threat stimulus.
Among the various materials found inside microplastic pollution, nanosized microplastics are of particular concern due to difficulties in quantification and detection; moreover, they are predicted to ...be abundant in aquatic environments with stronger toxicity than microsized microplastics. Here, we demonstrated a stronger accumulation of nanosized microbeads in the marine rotifer Brachionus koreanus compared to microsized ones, which was associated with oxidative stress-induced damages on lipid membranes. In addition, multixenobiotic resistance conferred by P-glycoproteins and multidrug resistance proteins, as a first line of membrane defense, was inhibited by nanoplastic pre-exposure, leading to enhanced toxicity of 2,2′,4,4′-tetrabromodiphenyl ether and triclosan in B. koreanus. Our study provides a molecular mechanistic insight into the toxicity of nanosized microplastics toward aquatic invertebrates and further implies the significance of synergetic effects of microplastics with other environmental persistent organic pollutants.
Cultured meat is a scientific product that can solve problems that future protein foods will confront (food security, solving environmental, diseases, etc.). Although much research has been conducted ...to solve these problems, challenges remain to be solved, such as cultured meat composition and scale-up. This paper reviews the current research on scaffolds, one solution to mass culturing, and discusses future directions. Scaffolds can solve problems (being slow and small in volume) of proliferation and the differentiation of cells that can occur in a single layer and have the advantage of being able to produce many cells at once. Many scaffold types, such as hydrogel, fiber scaffolds, and micro-carriers, have been created, and manufacturing methods have also been developed to allow cells to better attach and grow on these. Scaffolds are manufactured using methods such as three-dimensional printing, electrospinning and spraying, molding, and decellularization by mixing various materials. Collagen extracted from animal skin or tendons is most used, but vegetable proteins such as soybean, alginate, wheat, and corn, as well as edible microorganisms such as mold, are also used to manufacture scaffolds. For consumption, the manufacture of cultured meat should not only focus on awareness and mass production but should also complement the sensory characteristics of meat, such as texture and flavor. Therefore, the production of scaffolds should include components similar to those of meat, and more research will be needed to develop cultured meat with a scaffold similar to that of meat.
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•The need for 3D agricultural cell culture and various type scaffold.•Classification according to scaffold production methods in many ways.•Natural materials for 3D scaffold used in agricultural cell culture.•Development of cultured meat with texture and flavor similar to edible meat.•The need to develop scaffolds for industrialized massed cultured meat.
2D materials, such as graphene, exhibit great potential as functional materials for numerous novel applications due to their excellent properties. The grafting of conventional micropatterning ...techniques on new types of electronic devices is required to fully utilize the unique nature of graphene. However, the conventional lithography and polymer‐supported transfer methods often induce the contamination and damage of the graphene surface due to polymer residues and harsh wet‐transfer conditions. Herein, a novel strategy to obtain micropatterned graphene on polymer substrates using a direct curing process is demonstrated. Employing this method, entirely flexible, transparent, well‐defined self‐activated graphene sensor arrays, capable of gas discrimination without external heating, are fabricated on 4 in. wafer‐scale substrates. Finite element method simulations show the potential of this patterning technique to maximize the performance of the sensor devices when the active channels of the 2D material are suspended and nanoscaled. This study contributes considerably to the development of flexible functional electronic devices based on 2D materials.
A strategy to micropattern 2D materials on large‐scale flexible substrates using a direct polymer curing transfer method is demonstrated. Graphene microchannels on polymer substrates exhibit ultrahigh effective self‐heating under an applied bias voltage of less than 10 V. An entirely flexible and transparent chemical sensor array based on graphene micropatterns successfully discriminates gas species under the self‐activated state without external heating.
The extension of green and sustainable materials in the preparation of heterogeneous catalysts for organic transformations has increased over the past few decades. Because of their unique and ...intriguing physical and chemical properties, two-dimensional (2D) nanostructured materials have attracted widespread attention and have been used in a variety of applications, such as catalysis, electronics, and energy storage. A promising pathway to enhance the performance of 2D nanomaterials is their coupling with other functional materials to form heterogeneous or hybrid structures. Herein, we discuss the use of 2D-based nanostructured catalysts for enhancing organic transformations and highlight selected examples to demonstrate the synthesis, advantages, challenges, efficiency, and reusability of the introduced heterogeneous catalysts for cross-coupling and reduction reactions.
The hippocampus is crucial for retrieval of contextual memories. The activation of a subpopulation of neurons in the dorsal CA1 (dCA1) of the hippocampus is required for memory retrieval. Given that ...hippocampal neurons exhibit distinct patterns of response during memory retrieval, the activity patterns of individual neurons or ensembles may be critically involved in memory retrieval. However, this relation has been unclear. To investigate this question, we used an
microendoscope calcium imaging technique to optically record neuronal activity in the dCA1 of male and female mice. We observed that a portion of dCA1 neurons increased their responses to the learned context after contextual fear conditioning (FC), resulting in overall increase in response of neuronal population compared with simple context exposure. Such increased response was specific to the conditioned context as it disappeared in neutral context. The magnitude of increase in neuronal responses by FC was proportional to memory strength during retrieval. The increases in activity preferentially occurred during the putative sharp wave ripple events and were not simply because of animal's movement and immobility. At the ensemble level, synchronous cell activity patterns were associated with memory retrieval. Accordingly, when such patterns were more similar between conditioned and neutral context, animals displayed proportionally more similar level of freezing. Together, these results indicate that increase in responses of individual neurons and synchronous cell activity patterns in the dCA1 neuronal network are critically involved in representing a contextual memory recall.
Neurons in the dorsal CA1 of the hippocampus are crucial for memory retrieval. By using
calcium imaging methods for recording neuronal activity, we demonstrate that dCA1 neurons increased their responses to the learned context specifically by FC and such changes correlated with memory strength during retrieval. Moreover, distinct synchronous cell activity patterns were formed by FC and involved in representing contextual memory retrieval. These findings reveal dynamic activity features of dCA1 neurons that are involved in contextual memory retrieval.
This article proposes a disturbance observer (DOB)-based robust controller to improve the control performance of an electromagnetic actuator (EMA) with multiple electromagnets by compensating for the ...uncertainties caused by magnetic fields' nonlinearity and unmodeled magnetic properties. Conventional EMAs have been widely researched, but control strategies are limited to linearized magnetic field models based solely on intrinsic magnetic field strength. Thus, we designed a DOB-based double-loop feedback controller to extend the nominal feedback controller based on linearized magnetic field models. The DOB-based controller compensates for the unmodeled uncertainties and nonlinearities of multiple electromagnetic fields and improves performance in combination with the robustness of a conventional control scheme. The designed controller works as a force compensator for the target object and can widen the region of interest (ROI) of the given conventional EMA system without a scale-up design. Experimental results demonstrate that the proposed DOB-based controller improves the trajectory tracking error by 58.2% within the target ROI. Finally, the robustness of the proposed DOB-based controller for extended ROI is validated through a comparison with other control methods, which may increase the usefulness of the conventional EMA system.
P-glycoprotein (P-gp) overexpression is one of the major mechanisms of multidrug resistance (MDR). Previously, co-treatment with Janus kinase 2 (JAK2) inhibitors sensitized P-gp-overexpressing ...drug-resistant cancer cells. In this study, we assessed the cytotoxic effects of JAK2 inhibitor, fedratinib, on drug-resistant KBV20C cancer cells. We found that co-treatment with fedratinib at low doses induced cytotoxicity in KBV20C cells treated with vincristine (VIC). However, fedratinib-induced cytotoxicity was little effect on VIC-treated sensitive KB parent cells, suggesting that these effects are specific to resistant cancer cells. Fluorescence-activated cell sorting (FACS), Western blotting, and annexin V analyses were used to further investigate fedratinib's mechanism of action in VIC-treated KBV20C cells. We found that fedratinib reduced cell viability, increased G2 arrest, and upregulated apoptosis when used as a co-treatment with VIC. G2 phase arrest and apoptosis in VIC-fedratinib-co-treated cells resulted from the upregulation of p21 and the DNA damaging marker pH2AX. Compared with dimethyl sulfoxide (DMSO)-treated cells, fedratinib-treated KBV20C cells showed two-fold higher P-gp-inhibitory activity, indicating that VIC-fedratinib sensitization is dependent on the activity of fedratinib. Similar to VIC, fedratinib co-treatment with other antimitotic drugs (i.e., eribulin, vinorelbine, and vinblastine) showed increased cytotoxicity in KBV20C cells. Furthermore, VIC-fedratinib had similar cytotoxic effects to co-treatment with other JAK2 inhibitors (i.e., VIC-CEP-33779 or VIC-NVP-BSK805) at the same dose; similar cytotoxic mechanisms (i.e., early apoptosis) were observed between treatments, suggesting that co-treatment with JAK2 inhibitors is generally cytotoxic to P-gp-overexpressing resistant cancer cells. Given that fedratinib is FDA-approved, our findings support its application in the co-treatment of P-gp-overexpressing cancer patients showing MDR.
This article proposes a stacked-switched-capacitor stimulation (SSCS) system that can provide up to 9-V stimulation without using an external high-voltage (HV) supply or HV conversion stages to ...supply the stimulator. With the level-adaptive switch control, SSCS can be HV tolerant using only low-voltage (LV) transistors. In addition, SSCS achieves high stimulation efficiency up to 71.4%, which includes charging and discharging efficiencies of 72.6% and 99.9%, respectively, to charge 1-<inline-formula> <tex-math notation="LaTeX">\mu</tex-math> </inline-formula>F capacitor from 0 to 4 V by adopting the ac-to-capacitor charger and the stacked-capacitor stimulus discharger. Charge balancing (CB) can also be achieved in rapid time using the stimulus-synchronized CB (SS-CB) method which adaptively controls the pulsewidth of the recovery phase. The SSCS prototype verifies that the residual voltage up to 900 mV can be suppressed within four stimulation cycles and maintained within <inline-formula> <tex-math notation="LaTeX">\pm</tex-math> </inline-formula>30 mV by utilizing SS-CB.
Memory is supported by a specific collection of neurons distributed in broad brain areas, an engram. Despite recent advances in identifying an engram, how the engram is created during memory ...formation remains elusive. To explore the relation between a specific pattern of input activity and memory allocation, here we target a sparse subset of neurons in the auditory cortex and thalamus. The synaptic inputs from these neurons to the lateral amygdala (LA) are not potentiated by fear conditioning. Using an optogenetic priming stimulus, we manipulate these synapses to be potentiated by the learning. In this condition, fear memory is preferentially encoded in the manipulated cell ensembles. This change, however, is abolished with optical long-term depression (LTD) delivered shortly after training. Conversely, delivering optical long-term potentiation (LTP) alone shortly after fear conditioning is sufficient to induce the preferential memory encoding. These results suggest a synaptic plasticity-dependent competition rule underlying memory formation.
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