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Animals exhibit expressive facial movements in a wide range of behavioral contexts. However, the underlying neural mechanisms remain enigmatic. In reward-based learning tasks, mice make expressive movements with their whiskers and nose at the timings of reward expectation and acquisition. Here we show that optogenetic stimulation of midbrain dopamine neurons (oDAS) as a reward is sufficient to induce such expressive movements. Pavlovian conditioning with a sensory cue and oDAS elicited both cue-locked (reward-expecting) and oDAS-aligned (reward-acquiring) orofacial movements. Inhibition or knock-out of dopamine D1 receptors in the nucleus accumbens inhibited oDAS-induced motion but spared cue-locked motion. Silencing the whisker primary motor cortex (wM1) abolished both oDAS-induced and cue-locked orofacial movements. We found specific neuronal populations in wM1 representing either oDAS-aligned or cue-locked whisker movements. Thus, reward-acquiring and reward-expecting facial movements are driven by accumbal D1 receptor-dependent and -independent neuronal mechanisms, respectively, both dominantly regulated by wM1 activity.

This article describes an improvement in the noise reduction performance of a column correlated multiple sampling (CMS) readout circuit using interleaved pixel source follower for high-resolution and high-framerate CMOS image sensors (CISs). In this architecture, the time-interleaved operation of the two pixel source followers reduces the restrictions imposed by the settling time of the pixel source followers and extends the time for multiple sampling. The noise analysis indicates that this method has an advantage of enhanced noise reduction not only for thermal noise but also for 1/ ${f}$ noise when a high-speed readout operation is required. The measurement of the noise performance of the 8K image sensor using the CMS with the interleaved pixel source follower method exhibits a low input-referred noise of 3.2 e− at 8K 120 frames per second, while 4.6 e− with the conventional single-source follower readout method. The measurement results match reasonably well with the analysis presented in this article, demonstrating the effectiveness of the interleaved pixel source follower method for high-resolution and high-framerate CISs.

Major histocompatibility complex class II (MHC II) is important for the adaptive immune response because MHC II presents processed antigens to a cluster of differentiation 4 (CD4)-positive T-cells. Conventional doses of chemotherapeutic agents induce tumor cell death by causing DNA double-strand breaks (DSBs). However, cellular responses caused by sub-lethal doses of chemotherapeutic agents are poorly understood. In this study, using low doses of chemotherapeutic agents, we showed that DSBs enhanced the expression of MHC II on cells that originate from antigen-presenting cells (APCs). These agents induced the MHC class II transactivator (CIITA), the master regulator of MHC II, and interferon regulatory factor 1 (IRF1), a transcription factor for CIITA. Short hairpin RNA against IRF1 suppressed chemotherapeutic agent-induced CIITA expression, whereas exogenous expression of IRF1 induced CIITA. Inhibition of ataxia-telangiectasia mutated (ATM), a DSB-activated kinase, suppressed induction of IRF1, CIITA, and MHC II. Similar results were observed by inhibiting NF-κB, a downstream target of ATM. These results suggest that DSBs induce MHC II activity via the ATM-NF-κB-IRF1-CIITA pathway in cells that intrinsically present antigens. Additionally, chemotherapeutic agents induced T-cell regulatory molecules. Our findings suggest that chemotherapeutic agents enhance the antigen presentation activity of APCs for T-cell activation.

Small ball rebound hardness tests demonstrated characteristic hardening at 700 K in the ultra-low carbon and pearlitic steels. The equilibrium phase diagram of Fe-C binary alloy calculated using Thermo-Calc exhibited dissolving of cementite above 700 K. Moreover, in-situ heating neutron diffraction measurement demonstrated the increase of lattice parameter by dissolving of cementite above 700 K. Therefore, it can be concluded that the characteristic hardening above 700 K can be attributed to the solid solute carbon.

We developed an ultrahigh-definition (UHD)-2/8K camera recorder that uses a complementary metal–oxide semiconductor (CMOS) image sensor with an organic thin-film, instead of photodiodes for the opto-electrical conversion element. The advent of UHD-2/8K Super Hi-Vision broadcasts and an increase in the production of UHD-2/8K programs across a variety of genres necessitate the development of a sensor with a good signal-to-noise ratio (SNR) and high-dynamic range (HDR) to capture the full range of HDR video. To ensure successful use of this sensor, we studied the level diagrams (e.g., balancing of sensitivity, SNR, and dynamic range) that would best fit the sensor’s characteristics and use its strengths, and then proceeded accordingly. For the current UHD-2/8K location shooting, a workflow is needed to record raw data and post-process them into a practical video format. To implement a more efficient workflow, we chose to use Grass Valley HQX compression encoding while adding features that make it possible to store video data in a compressed form and simultaneously generate high-definition television (HDTV) proxy data. The workflow that we envisioned uses proxy data for offline editing and relinks them using online editing equipment.

Volatile anesthetics are widely used for surgery, but neuronal mechanisms of anesthesia remain unidentified. At the calyx of Held in brainstem slices from rats of either sex, isoflurane at clinical doses attenuated EPSCs by decreasing the release probability and the number of readily releasable vesicles. In presynaptic recordings of Ca2+currents and exocytic capacitance changes, isoflurane attenuated exocytosis by inhibiting Ca2+currents evoked by a short presynaptic depolarization, whereas it inhibited exocytosis evoked by a prolonged depolarization via directly blocking exocytic machinery downstream of Ca2+influx. Since the length of presynaptic depolarization can simulate the frequency of synaptic inputs, isoflurane anesthesia is likely mediated by distinct dual mechanisms, depending on input frequencies. In simultaneous presynaptic and postsynaptic action potential recordings, isoflurane impaired the fidelity of repetitive spike transmission, more strongly at higher frequencies. Furthermore, in the cerebrum of adult mice, isoflurane inhibited monosynaptic corticocortical spike transmission, preferentially at a higher frequency. We conclude that dual presynaptic mechanisms operate for the anesthetic action of isoflurane, of which direct inhibition of exocytic machinery plays a low-pass filtering role in spike transmission at central excitatory synapses.SIGNIFICANCE STATEMENTSynaptic mechanisms of general anesthesia remain unidentified. In rat brainstem slices, isoflurane inhibits excitatory transmitter release by blocking presynaptic Ca2+channels and exocytic machinery, with the latter mechanism predominating in its inhibitory effect on high-frequency transmission. Both in slice andin vivo, isoflurane preferentially inhibits spike transmission induced by high-frequency presynaptic inputs. This low-pass filtering action of isoflurane likely plays a significant role in general anesthesia.

In-situ neutron diffraction measurements during tensile tests at low temperatures of a low alloy steel containing retained austenite (γ) have been performed. Evolutions of phase fractions and phase stresses were analyzed and discussed with the progress of deformation. The role of γ in the steel during deformation at low temperatures was observed not to directly in the contribution to the strengths but in the improvement of the elongation by transformation of γ to martensite -and in the increasing of the work-hardening rate by an increase in the phase fraction of martensite and the work hardening of martensite.

Psychosocial stress can impact feeding behavior outcomes. Although many studies have examined alterations to food intake, little is known about how stress affects feeding behavior patterns. To determine the impact of psychological stress on feeding behavior patterns, mice were subjected to various psychosocial stressors (social isolation, intermittent high-fat-diet, or physical restraint) prior to timed observations in a feeding arena that incorporated multiple bait loci. In addition, in vivo microdialysis was used to assess the effects of stressors on the reward system by measuring dopamine levels in the nucleus accumbens (NAcc) shell. Impaired feeding behavior patterns characterized by significant deviations in bait selection (i.e. fixated feeding) and prolonged periods of eating (i.e. protracted feeding) were observed in stressed mice relative to non-stressed controls. In addition to clear behavioral effects, the stressors also negatively impacted dopamine levels at the nucleus accumbens shell. Normalization of dopamine reversed the fixated feeding behavior, whereas specifically inhibiting neuronal activity in the dopaminergic neurons of the ventral tegmental area that project to the nucleus accumbens shell caused similar impairments in feeding. Given that the deviations were not consistently accompanied by changes in the amount of bait consumed, body weight, or metabolic factors, the qualitative effects of psychosocial stressors on feeding behavior likely reflect perturbations to a critical pathway in the mesolimbic dopamine system. These findings provide compelling evidence that aberrations in feeding behavior patterns can be developed as sensitive biomarkers of psychosocial stress and possibly a prodromal state of neuropsychiatric diseases.Significance StatementFeeding behavior can be affected by neuropsychiatric disorders including psychosocial stressors, and the evaluation of eating behavior was mainly based on food intake. However, it is speculated that not only food intake but also feeding behavior patterns can be affected in such disorders. The biological processes underlying the feeding behavior patterns have not been clarified yet. We found that aberrant feeding behaviors in mice characterized by fixated feeding were provoked by psychosocial stressors. The qualitative effects of psychosocial stressors on feeding behavior reflect perturbations in the mesolimbic dopamine system. These findings provide compelling evidence that aberrations in feeding behavior patterns can be developed as sensitive biomarkers of psychosocial stress and possibly a prodromal state of neuropsychiatric diseases.

Titanium has a significant potential for the cryogenic industrial fields such as aerospace and liquefied gas storage and transportation due to its excellent low temperature properties. To develop and advance the technologies in cryogenic industries, it is required to fully understand the underlying deformation mechanisms of Ti under the extreme cryogenic environment. Here, we report a study of the lattice behaviour in grain families of Grade 2 CP-Ti during in-situ neutron diffraction test in tension at temperatures of 15–298 K. Combined with the neutron diffraction intensity analysis, EBSD measurements revealed that the twinning activity was more active at lower temperature, and the behaviour was complicated with decreasing temperature. The deviation of linearity in the lattice strains was caused by the load-redistribution between plastically soft and hard grain families, resulting in the three-stage hardening behaviour. The lattice strain behaviour further deviated from linearity with decreasing temperature, leading to the transition of plastically soft-to-hard or hard-to-soft characteristic of particular grain families at cryogenic temperature. The improvement of ductility can be attributed to the increased twinning activity and a significant change of lattice deformation behaviour at cryogenic temperature.

Microbial rhodopsins widely used for optogenetics are sensitive to light in the visible spectrum. As visible light is heavily scattered and absorbed by tissue, stimulating light for optogenetic control does not reach deep in the tissue irradiated from outside the subject body. Conventional optogenetics employs fiber optics inserted close to the target, which is highly invasive and poses various problems for researchers. Recent advances in material science integrated with neuroscience have enabled remote optogenetic control of neuronal activities in living animals using up- or down-conversion phosphors. The development of these methodologies has stimulated researchers to test novel strategies for less invasive, wireless control of cellular functions in the brain and other tissues. Here, we review recent reports related to these new technologies and discuss the current limitations and future perspectives toward the establishment of non-invasive optogenetics for clinical applications.

Barrington's nucleus (Bar), which controls micturition behavior through downstream projections to the spinal cord, contains two types of projection neurons, BarCRH and BarESR1, that have different functions and target different spinal circuitry. Both types of neurons project to the L6-S1 spinal intermediolateral (IML) nucleus, whereas BarESR1 neurons also project to the dorsal commissural nucleus (DCN). To obtain more information about the spinal circuits targeted by Bar, we used patch-clamp recording in spinal slices from adult mice in combination with optogenetic stimulation of Bar terminals. Recording of opto-evoked excitatory postsynaptic currents (oEPSCs) in 1,1'-dilinoleyl-3,3,3',3'-tetramethylindocarbocyanine, 4-chlorobenzenesulfonate (DiI)-labeled lumbosacral preganglionic neurons (LS-PGNs) revealed that both Bar neuronal populations make strong glutamatergic monosynaptic connections with LS-PGNs, whereas BarESR1 neurons also elicited smaller-amplitude glutamatergic polysynaptic oEPSCs or polysynaptic opto-evoked inhibitory postsynaptic currents (oIPSCs) in some LS-PGNs. Optical stimulation of BarCRH and BarESR1 terminals also elicited monosynaptic oEPSCs and polysynaptic oIPSCs in sacral DCN neurons, some of which must include interneurons projecting to either the IML or ventral horn. Application of capsaicin increased opto-evoked firing during repetitive stimulation of Bar terminals through the modulation of spontaneous postsynaptic currents in LS-PGNs. In conclusion, our experiments have provided insights into the synaptic mechanisms underlying the integration of inputs from Bar to autonomic circuitry in the lumbosacral spinal cord that may control micturition.NEW & NOTEWORTHY Photostimulation of BarCRH or BarESR1 axons in the adult mouse spinal cord elicits excitatory or inhibitory postsynaptic responses in multiple cell types related to the autonomic nervous system including preganglionic neurons (PGNs) in the lumbosacral intermediolateral nucleus and interneurons in the lumbosacral dorsal commissure nucleus. Integration of excitatory inputs from Bar and from visceral primary afferents in PGNs may be important in the regulation of micturition behavior.

This paper describes the noise reduction effect of a folding-integration (FI) ADC applied to an 8K image sensor. To maximize the sampling number in correlated multiple sampling (CMS), we implement duplicated pixel source followers, which are operated alternately to reduce the time needed for them to settle. This architecture facilitates sampling numbers of 6, 14, and 30 at 120, 60, and 30 fps, respectively. To investigate the relationship between noise reduction effect and sampling number, the input referred noise of the readout circuit from the pixel-to-column ADC is estimated via theoretical calculations and compared with measurements. As a result, the random noise levels of 3.2, 2.0, and 1.5 e- were measured at sampling numbers of 6, 14, and 30, respectively, corresponding well with the calculated results. Furthermore, theoretical calculations revealed that the thermal noise component is dominant at higher frame rates while 1/f noise from the source follower becomes dominant at lower frame rates.

A phase detection (PD) autofocus (AF) method for three-chip color imaging cameras is proposed. The method detects the focus state of a lens by calculating the disparity between a half-shielded PD pixel and other normal pixels corresponding to the same incident position among three sensors, which can perform accurate AF without employing state-of-the-art dual-photodiode technology. By using a prototype 8K sensor with half-shielded PD pixels (PD sensor), we demonstrated that installing the PD sensor into a blue channel of the three-chip system can achieve an excellent phase separation ratio and robust disparity calculation with less image quality degradation due to defects of PD pixels.

The SWI/SNF chromatin remodeling complex regulates transcription through the control of chromatin structure and is increasingly thought to play an important role in human cancer. Lung adenocarcinoma (LADC) patients frequently harbor mutations in SMARCA4, a core component of this multisubunit complex. Most of these mutations are loss-of-function mutations, which disrupt critical functions in the regulation of chromatin architecture and can cause DNA replication stress. This study reports that LADC cells deficient in SMARCA4 showed increased DNA replication stress and greater sensitivity to the ATR inhibitor (ATRi) in vitro and in vivo. Mechanistically, loss of SMARCA4 increased heterochromatin formation, resulting in stalled forks, a typical DNA replication stress. In the absence of SMARCA4, severe ATRi-induced single-stranded DNA, which caused replication catastrophe, was generated on nascent DNA near the reversed forks around heterochromatin in an Mre11-dependent manner. Thus, loss of SMARCA4 confers susceptibility to ATRi, both by increasing heterochromatin-associated replication stress and by allowing Mre11 to destabilize reversed forks. These two mechanisms synergistically increase susceptibility of SMARCA4-deficient LADC cells to ATRi. These results provide a preclinical basis for assessing SMARCA4 defects as a biomarker of ATRi efficacy.

Focusing difficulty has become a critical issue in 8K ultra-high definition television (UHDTV) production. Especially in 8K high-speed shooting, defocus blur significantly degrades a user's experience of slow-motion playback video. For this reason, incorporating a sensor-based phase detection autofocus (PDAF) system that can adjust the focus of a lens quickly into an 8K UHDTV camera has been strongly desired. Although conventional sensor-based PDAF systems have been designed for single-chip cameras capable of using optional color filters, the application of phase detection (PD) in professional broadcasting cameras with three-chip imaging has not been studied, in which incident light separates into three color components (red, green, and blue) by a separation prism. This paper presents an investigation into the PD property among the color channels using a newly prototyped 1.25-inch 8K 240-fps complementary metal-oxide-semiconductor (CMOS) image sensor with two types of horizontal PD pixels (left- and right-phase). Our experiment showed that crosstalk over angler responses of the PD sensor became larger as the wavelength of light increased, and that the crosstalk in each color component reduced the accuracy of the PD amount between a set of stereo images. Consequently, these results demonstrated that utilizing the phase-differential information from the blue component enables a high-precision sensor-based PDAF operation in three-CMOS imaging when shooting black and white objects