Enhancement of Haloperidol-Induced Catalepsy by GPR143, an L-Dopa Receptor, in Striatal Cholinergic Interneurons.

Dopamine neurons play crucial roles in pleasure, reward, memory, learning, and fine motor skills and their dysfunction is associated with various neuropsychiatric diseases. Dopamine receptors are the main target of treatment for neurologic and psychiatric disorders. Antipsychotics that antagonize the dopamine D2 receptor (DRD2) are used to alleviate the symptoms of these disorders but may also sometimes cause disabling side effects such as parkinsonism (catalepsy in rodents). Here we show that GPR143, a G-protein-coupled receptor for L-3,4-dihydroxyphenylalanine (L-DOPA), expressed in striatal cholinergic interneurons enhances the DRD2-mediated side effects of haloperidol, an antipsychotic agent. Haloperidol-induced catalepsy was attenuated in male Gpr143 gene-deficient (Gpr143-/y ) mice compared with wild-type (Wt) mice. Reducing the endogenous release of L-DOPA and preventing interactions between GPR143 and DRD2 suppressed the haloperidol-induced catalepsy in Wt mice but not Gpr143-/y mice. The phenotypic defect in Gpr143-/y mice was mimicked in cholinergic interneuron-specific Gpr143-/y (Chat-cre;Gpr143flox/y ) mice. Administration of haloperidol increased the phosphorylation of ribosomal protein S6 at Ser240/244 in the dorsolateral striatum of Wt mice but not Chat-cre;Gpr143flox/y mice. In Chinese hamster ovary cells stably expressing DRD2, co-expression of GPR143 increased cell surface expression level of DRD2, and L-DOPA application further enhanced the DRD2 surface expression. Shorter pauses in cholinergic interneuron firing activity were observed after intrastriatal stimulation in striatal slice preparations from Chat-cre;Gpr143flox/y mice compared with those from Wt mice. Together, these findings provide evidence that GPR143 regulates DRD2 function in cholinergic interneurons and may be involved in parkinsonism induced by antipsychotic drugs.

Porphyrin-Polyoxotungstate Molecular Hybrid as a Highly Efficient, Durable, Visible-Light-Responsive Photocatalyst for Aerobic Oxidation Reactions.

Organic-polyoxometalate (POM) hybrids have recently attracted considerable interest because of their distinctive properties and wide-ranging applications. For the construction of organic-POM hybrids, porphyrins are promising building units owing to their optical properties and reactivity, including strong visible-light absorption and subsequent singlet-oxygen (1O2*) generation. However, the practical utilization of porphyrins as photocatalysts and photosensitizers is often hindered by their own degradation by 1O2*. Therefore, there is a substantial demand for the development of porphyrin-derived photocatalysts with both high efficiency and durability. Herein, we present a porphyrin-polyoxotungstate molecular hybrid featuring a face-to-face stacked porphyrin dimer (I) fastened by four lacunary polyoxotungstates. Hybrid I exhibited remarkable efficiency and durability in photocatalytic aerobic oxidation reactions, and the selective oxidation of various dienes, alkenes, sulfides, and amines proceeded using just 0.003 mol % of the catalyst. Mechanistic investigations suggested that the high activity of I stems from the efficient generation of 1O2*, resulting from the heavy-atom effect of POMs. Furthermore, despite its high efficiency in 1O2* generation compared to free porphyrins, I exhibited superior durability against 1O2*-induced degradation under photoirradiation.

Hepatitis B surface antigen (HBsAg) glycan isomer is predictive of HBsAg seroclearance in patients with chronic hepatitis B.

AIM: Measurement of O-glycosylated middle hepatitis B surface antigen (HBsAg glycan isomer, HBsAgGi) has been developed to quantify hepatitis B virus (HBV) infectious virions and distinguish them from subviral particles. This study aimed to evaluate the association between serum HBsAg seroclearance and serum HBV virions measured by HBsAgGi in patients with chronic hepatitis B (CHB). METHODS: Serum HBsAgGi levels were quantified in 232 treatment-naïve patients with CHB genotype C. Cox proportional hazards analysis was used to calculate hazard ratios (HRs) for factors associated with HBsAg seroclearance. RESULTS: Baseline HBsAgGi levels showed significant differences among HBV phenotypes. During a median follow-up period of 7.4 years, 22 of the 232 patients achieved HBsAg seroclearance. Multivariate analysis demonstrated that quantitative HBsAg, nucleoside/nucleotide analog therapy during the follow-up period, and HBsAgGi levels were independent predictors of seroclearance. The adjusted HR indicated that the HBsAg seroclearance probability in patients with low HBsAgGi (≤3.5log ng/mL) was over five times higher than that in patients with high HBsAgGi. Kaplan-Meier analysis indicated that the 10-year probabilities of HBsAg seroclearance were 21.0% and 3.0% in patients with low and high HBsAgGi levels, respectively (p < 0.001), and that patients with high HBsAgGi levels showed low seroclearance probabilities irrespective of the other predictors. CONCLUSION: Serum HBV infectious virion levels, measured using HBsAgGi, may be a novel predictor of HBsAg seroclearance.

Color Standardization and Stain Intensity Calibration for Whole Slide Image-Based Immunohistochemistry Assessment.

Automated quantification of human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) using whole slide imaging (WSI) is expected to eliminate subjectivity in visual assessment. However, the color intensity in WSI varies depending on the staining process and scanner device. Such variations affect the image analysis results. This paper presents methods to diminish the influence of color variation produced in the staining process using a calibrator slide consisting of peptide-coated microbeads. The calibrator slide is stained along with tissue sample slides, and the 3,3'-diaminobenzidine (DAB) color intensities of the microbeads are used for calibrating the color variation of the sample slides. An off-the-shelf image analysis tool is employed for the automated assessment, in which cells are classified by the thresholds for the membrane staining. We have adopted two methods for calibrating the color variation based on the DAB color intensities obtained from the calibrator slide: (1) thresholds for classifying the DAB membranous intensity are adjusted, and (2) the color intensity of WSI is corrected. In the experiment, the calibrator slides and tissue of breast cancer slides were stained together on different days and used to test our protocol. With the proposed protocol, the discordance in the HER2 evaluation was reduced to one slide out of 120 slides.

MAP KINASE PHOSPHATASE1 promotes osmotolerance by suppressing PHYTOALEXIN DEFICIENT4-independent immunity.

Initial exposure of plants to osmotic stress caused by drought, cold, or salinity leads to acclimation, termed acquired tolerance, to subsequent severe stresses. Acquired osmotolerance induced by salt stress is widespread across Arabidopsis (Arabidopsis thaliana) accessions and is conferred by disruption of a nucleotide-binding leucine-rich repeat gene, designated ACQUIRED OSMOTOLERANCE. De-repression of this gene under osmotic stress causes detrimental autoimmunity via ENHANCED DISEASE SUSCEPTIBILITY1 and PHYTOALEXIN DEFICIENT4 (PAD4). However, the mechanism underlying acquired osmotolerance remains poorly understood. Here, we isolated an acquired osmotolerance-defective mutant (aod13) by screening 30,000 seedlings of an ion beam-mutagenized M2 population of Bu-5, an accession with acquired osmotolerance. We found that AOD13 encodes the dual-specificity phosphatase MAP KINASE PHOSPHATASE1 (MKP1), which negatively regulates MITOGEN-ACTIVATED PROTEIN KINASE3/6 (MPK3/6). Consistently, MPK3/6 activation was greater in aod13 than in the Bu-5 wild-type (WT). The aod13 mutant was sensitive to osmotic stress but tolerant to salt stress. Under osmotic stress, pathogenesis-related genes were strongly induced in aod13 but not in the Bu-5 WT. Loss of PAD4 in pad4 aod13 plants did not restore acquired osmotolerance, implying that activation of immunity independent of PAD4 renders aod13 sensitive to osmotic stress. These findings suggest that AOD13 (i.e. MKP1) promotes osmotolerance by suppressing the PAD4-independent immune response activated by MPK3/6.

Wave-optics-based image synthesis for super resolution reconstruction of a FZA lensless camera.

A Fresnel Zone Aperture (FZA) mask for a lensless camera, an ultra-thin and functional computational imaging system, is beneficial because the FZA pattern makes it easy to model the imaging process and reconstruct captured images through a simple and fast deconvolution. However, diffraction causes a mismatch between the forward model used in the reconstruction and the actual imaging process, which affects the recovered image's resolution. This work theoretically analyzes the wave-optics imaging model of an FZA lensless camera and focuses on the zero points caused by diffraction in the frequency response. We propose a novel idea of image synthesis to compensate for the zero points through two different realizations based on the linear least-mean-square-error (LMSE) estimation. Results from computer simulation and optical experiments verify a nearly two-fold improvement in spatial resolution from the proposed methods compared with the conventional geometrical-optics-based method.

Image quality assessment procedure for holographic displays based on exact numerical reconstruction of computer-generated holograms.

We proposed a technique for the computer-based reconstruction of computer-generated holograms and evaluation of the reconstructed 3D image quality. The proposed method mimics how the eye's lens works, thus allowing for viewing position and eye focus adjustments. The angular resolution of the eye was used to output reconstructed images with the requisite resolution, and a reference object was used to normalize the images. Such data processing enables the numerical analysis of image quality. By comparing the reconstructed images with the original image with incoherent illumination, the image quality was quantitatively evaluated.

Risk of eating disorders and the relationship with interest in modern culture among young female students in a university in Bangladesh: a cross-sectional study.

BACKGROUND: Eating disorders (EDs) emerge most often in adolescent girls. While the basic neural and psychiatric mechanisms of ED development remain unknown, their incidence has increased with sociocultural modernization. To determine what aspects of modern culture are related to EDs, we examined the relationship between predisposition to EDs and interest in several modern cultural factors among young female university students in Bangladesh. METHODS: A cross-sectional study was conducted in a population of 196 female students aged 18-29 years in a university in Bangladesh. Their predisposition to EDs was examined using the Eating Attitudes Test-26 (EAT-26), and their interest in modern culture was evaluated by grading interest in fashionable clothes, Indian TV shows/serials, luxury food and social network activities, and by examining involvement in cultural activities such as playing, dancing, parties and singing. The relationship between predisposition to EDs and interest in modern culture was then examined. The relation between EAT-26 score and body mass index (BMI) was also examined. RESULTS: The EAT-26 revealed that 37% of the participants were at risk of developing an ED. Correlation analyses showed that a high EAT-26 score was correlated with a high interest in fashionable clothes and Indian TV shows/serials, but not with a high interest in luxury food or social network activities, or involvement in cultural activities, such as playing, dancing, parties and singing. Further, EAT-26 questions in the dieting category and oral control category, but not the bulimia and food preoccupation category, were correlated with interest in cultural factors. EAT-26 score showed no significant correlation with BMI. CONCLUSIONS: The results of this study indicate that the risk of EDs is related to an interest in several facets of modern culture. Monitoring the cultural interests of adolescent females, who are continually exposed to modern culture and highly susceptible to EDs, will contribute to the prevention of EDs.

Seasonal variations in the amount of black carbon particles deposited on the leaf surfaces of nine Japanese urban greening tree species and their related factors.

As black carbon (BC) particles can be deposited on the leaf surfaces, urban greening is considered to be effective in purifying urban air. However, little information on the seasonal variations in the amount of BC particles deposited on the leaf surfaces (BC amount on the leaves) is available in Japanese urban greening tree species. Therefore, we investigated seasonal variations in the BC amount on the leaves of evergreen (Quercus glauca, Quercus myrsinaefolia, Osmanthus fragrans and Ilex rotunda) and deciduous (Zelkova serrata, Styrax japonica, Magnolia kobus, Cornus kousa and Cornus florida) broad-leaved tree species. The BC amount on the leaves tended to increase from April for different periods, and then reached a saturated state in the tree species, excluding M. kobus. In the 4 evergreen broad-leaved trees, the seasonal variation was positively correlated with the atmospheric concentration of BC particle. In the 5 deciduous broad-leaved trees, the seasonal variation was negatively and positively correlated with the water-repellence (water droplet contact angle) and the amount of epicuticular wax on the leaf surface, respectively. Therefore, the BC amounts on the leaves of evergreen and deciduous broad-leaved urban tree species are considered to be mainly regulated by environmental factors and leaf surface characteristics, respectively.

This is the first paper that reports the seasonal variations in the amount of BC particles deposited on the leaves of Japanese urban greening tree species and their related factors such as environmental conditions and leaf surface characteristics. This study will provide the basic and novel information for the phytoremediation of urban air pollution induced by BC particles in Asia.

Relationship between the amount of black carbon particles deposited on the leaf surface and leaf surface traits in nine urban greening tree species.

To select urban greening tree species suitable for the purification of the atmosphere polluted by black carbon (BC) particles, it is necessary to clarify the determinants of the amount of BC particles deposited on the tree leaves. In the present study, we investigated the relationship between the amount of BC particles that were deposited from the atmosphere and firmly adhered to the leaf epicuticular wax, and leaf surface traits in seedlings of nine tree species grown for two years under natural conditions (Fuchu, Tokyo, Japan). There was a significant interspecific difference in the maximum amount of BC particles deposited on the leaf surface, and the order was as follows: Ilex rotunda > Cornus florida > Osmanthus fragrans > Cornus kousa > Quercus glauca ≒ Quercus myrsinifolia > Magnolia kobus ≒ Zelkova serrata ≒ Styrax japonicus. In the nine tree species, significant highly positive correlations were observed between the amount of BC particles deposited on the leaf surface, and the hydrophobicity of leaf epicuticular wax determined by its chemical composition. Therefore, we concluded that the hydrophobicity of leaf epicuticular wax is an important determinant of the amount of BC particles deposited on the leaf surface of urban greening tree species.

This is the first paper that shows that the hydrophobicity of leaf epicuticular wax is an important determinant of the amount of BC particles deposited on the leaf surface of urban greening tree species. This study will provide the basic and novel information for the selection of urban greening tree species suitable for the purification of the air polluted by BC particles.

Therapeutic Potential of Orally Administered Rubiscolin-6.

Rubiscolins are naturally occurring opioid peptides derived from the enzymatic digestion of the ribulose bisphosphate carboxylase/oxygenase protein in spinach leaves. They are classified into two subtypes based on amino acid sequence, namely rubiscolin-5 and rubiscolin-6. In vitro studies have determined rubiscolins as G protein-biased delta-opioid receptor agonists, and in vivo studies have demonstrated that they exert several beneficial effects via the central nervous system. The most unique and attractive advantage of rubiscolin-6 over other oligopeptides is its oral availability. Therefore, it can be considered a promising candidate for the development of a novel and safe drug. In this review, we show the therapeutic potential of rubiscolin-6, mainly focusing on its effects when orally administered based on available evidence. Additionally, we present a hypothesis for the pharmacokinetics of rubiscolin-6, focusing on its absorption in the intestinal tract and ability to cross the blood-brain barrier.

Computational see-through screen camera based on a holographic waveguide device.

This study proposes a novel computational imaging system that integrates a see-through screen (STS) with volume holographic optical elements (vHOEs) and a digital camera unit. Because of the unique features of the vHOE, the STS can function as a holographic waveguide device (HWD) and enable the camera to capture the frontal image when the user gazes at the screen. This system not only provides an innovative solution to a high-quality video communication system by realizing eye-contact but also contributes to other visual applications due to its refined structure. However, there is a dilemma in the proposed imaging system: for a wider field of view, a larger vHOE is necessary. If the size of the vHOE is larger, the light rays from the same object point are diffracted at different Bragg conditions and reflect a different number of times, which causes blurring of the captured image. The system imaging process is analyzed by ray tracing, and a digital image reconstruction method was employed to obtain a clear picture in this study. Optical experiments confirmed the effectiveness of the proposed HWD-STS camera.

Thyroid hormone-dependent and independent processes of red blood cell transition from larval to adult type during metamorphosis in Xenopus laevis.

Amphibian metamorphosis results in drastic whole-body remodeling. Thyroid hormone (TH) drives most of these metamorphic changes. A prominent event during this remodeling is the red blood cell (RBC) transition from larval to adult forms, which exclusively contain larval and adult hemoglobin, respectively. However, the role of TH in RBC transition remains unclear. Here we reconfirmed that RBC transition of Xenopus laevis is completed much later than morphological metamorphosis. Further, larval and adult RBCs/erythroblasts proliferated both in the erythropoietic liver and in circulation during metamorphic climax. RBC transition was also confirmed in Rana ornativentris, but in contrast to X. laevis, adult RBC-specific proliferation was observed from the early climax stages. We also revealed in either species that RBC transition occurs in the liver prior to circulating RBCs. Moreover, anemia induction using phenylhydrazine during the prometamorphosis of X. laevis caused precocious RBC transition even when TH synthesis was blocked, resulting in metamorphosis-arrested larvae in which most of RBCs were of adult type. These results indicate that a decline in larval RBCs facilitates RBC transition during metamorphosis in a TH-independent manner. Further, combined administration of phenylhydrazine and TH induced precocious appearance of adult RBCs in early prometamorphic X. laevis tadpoles, whereas individual treatment with phenylhydrazine or TH did not cause precocious RBC transition; this suggests that TH is required to initiate RBC transition by promoting the differentiation of adult erythroblasts during early prometamorphosis in X. laevis. These results show that TH-dependent and independent processes are present in RBC transition in X. laevis.

Image reconstruction with transformer for mask-based lensless imaging.

A mask-based lensless camera optically encodes the scene with a thin mask and reconstructs the image afterward. The improvement of image reconstruction is one of the most important subjects in lensless imaging. Conventional model-based reconstruction approaches, which leverage knowledge of the physical system, are susceptible to imperfect system modeling. Reconstruction with a pure data-driven deep neural network (DNN) avoids this limitation, thereby having potential to provide a better reconstruction quality. However, existing pure DNN reconstruction approaches for lensless imaging do not provide a better result than model-based approaches. We reveal that the multiplexing property in lensless optics makes global features essential in understanding the optically encoded pattern. Additionally, all existing DNN reconstruction approaches apply fully convolutional networks (FCNs) which are not efficient in global feature reasoning. With this analysis, for the first time to the best of our knowledge, a fully connected neural network with a transformer for image reconstruction is proposed. The proposed architecture is better in global feature reasoning, and hence enhances the reconstruction. The superiority of the proposed architecture is verified by comparing with the model-based and FCN-based approaches in an optical experiment.

Evaluation of the Intracellular Signaling Activities of κ-Opioid Receptor Agonists, Nalfurafine Analogs; Focusing on the Selectivity of G-Protein- and ß-Arrestin-Mediated Pathways.

Opioid receptors (ORs) are classified into three types (µ, δ, and κ), and opioid analgesics are mainly mediated by µOR activation; however, their use is sometimes restricted by unfavorable effects. The selective κOR agonist nalfurafine was initially developed as an analgesic, but its indication was changed because of the narrow safety margin. The activation of ORs mainly induces two intracellular signaling pathways: a G-protein-mediated pathway and a ß-arrestin-mediated pathway. Recently, the expectations for κOR analgesics that selectively activate these pathways have increased; however, the structural properties required for the selectivity of nalfurafine are still unknown. Therefore, we evaluated the partial structures of nalfurafine that are necessary for the selectivity of these two pathways. We assayed the properties of nalfurafine and six nalfurafine analogs (SYKs) using cells stably expressing κORs. The SYKs activated κORs in a concentration-dependent manner with higher EC50 values than nalfurafine. Upon bias factor assessment, only SYK-309 (possessing the 3S-hydroxy group) showed higher selectivity of G-protein-mediated signaling activities than nalfurafine, suggesting the direction of the 3S-hydroxy group may affect the ß-arrestin-mediated pathway. In conclusion, nalfurafine analogs having a 3S-hydroxy group, such as SYK-309, could be considered G-protein-biased κOR agonists.

Lensless inference camera: incoherent object recognition through a thin mask with LBP map generation.

We propose a preliminary lensless inference camera (LLI camera) specialized for object recognition. The LLI camera performs computationally efficient data preprocessing on the optically encoded pattern through the mask, rather than performing computationally expensive image reconstruction before inference. Therefore, the LLI camera avoids expensive computation and achieves real-time inference. This work proposes a new data preprocessing approach, named local binary patterns map generation, dedicated for optically encoded pattern through the mask. This preprocessing approach greatly improves encoded pattern's robustness to local disturbances in the scene, making the LLI camera's practical application possible. The performance of the LLI camera is analyzed through optical experiments on handwritten digit recognition and gender estimation under conditions with changing illumination and a moving target.

Incoherent reconstruction-free object recognition with mask-based lensless optics and the Transformer.

A mask-based lensless camera adopts a thin mask to optically encode the scene and records the encoded pattern on an image sensor. The lensless camera can be thinner, lighter and cheaper than the lensed camera. But additional computation is required to reconstruct an image from the encoded pattern. Considering that the significant application of the lensless camera could be inference, we propose to perform object recognition directly on the encoded pattern. Avoiding image reconstruction not only saves computational resources but also averts errors and artifacts in reconstruction. We theoretically analyze multiplexing property in mask-based lensless optics which maps local information in the scene to overlapping global information in the encoded pattern. To better extract global features, we propose a simplified Transformer-based architecture. This is the first time to study Transformer-based architecture for encoded pattern recognition in mask-based lensless optics. In the optical experiment, the proposed system achieves 91.47% accuracy on the Fashion MNIST and 96.64% ROC AUC on the cats-vs-dogs dataset. The feasibility of physical object recognition is also evaluated.

Roadmap on digital holography [Invited].

This Roadmap article on digital holography provides an overview of a vast array of research activities in the field of digital holography. The paper consists of a series of 25 sections from the prominent experts in digital holography presenting various aspects of the field on sensing, 3D imaging and displays, virtual and augmented reality, microscopy, cell identification, tomography, label-free live cell imaging, and other applications. Each section represents the vision of its author to describe the significant progress, potential impact, important developments, and challenging issues in the field of digital holography.

Naked-eye detection of specific DNA sequences amplified by the polymerase chain reaction with nanocomposite beads.

We developed a novel nanocomposite bead system for detection by the naked eye of specific DNA sequences amplified by the polymerase chain reaction (PCR). The DNA probes, which were complementary to the target DNA, are conjugated with the nanocomposite beads. If the amplified products contained sequences complementary to the probes, the beads aggregated through sandwich hybridization. The aggregation was detectable as precipitation of the nanocomposite beads. The results were determined visually and did not require instrumental detection. The assay was sensitive enough to detect PCR products with a detection limit of 10 copies/tube for DNA templates. This technique is that all needed components are included within the initial cap, so that the risk of carryover contamination is very low. The nanocomposite bead system has broad application prospects for the detection of specific DNA sequences in biological and biomedical research.

See-through aerial display using a dihedral corner reflector array and hologram mirrors.

In this study, we reveal a novel aerial display system, to the best of our knowledge, that combines volume hologram mirrors with a dihedral corner reflector array (DCRA). The suggested aerial display has a see-through capability, which allows for a new design of aerial displays by combining with other types of displays. Furthermore, the virtual image, which frequently disrupts the observation of aerial images, can be suppressed by the Bragg condition of the volume hologram. The color dispersion in the holograms is efficiently compensated by employing features of the DCRA. The findings of preliminary experiments are demonstrated using a DCRA device and full-color hologram mirrors.