Development of novel potent ligands for GPR85, an orphan G protein-coupled receptor expressed in the brain.

GPR85 is a member of the G protein-coupled receptor and is a super-conserved receptor expressed in the brain sub-family (Super Conserved Receptor Expressed in Brain; SREB) with GPR27 and GPR173. These three receptors are "orphan receptors"; however, their endogenous ligands have not been identified. SREB has garnered the interest of many scientists because it is expressed in the central nervous system and is evolutionarily conserved. In particular, brain mass is reported to be increased and learning and memory are improved in GPR85 knockout mice (Matsumoto et al. 2008). In this study, we characterized newly synthesized compounds using a GPR85-Gsα fusion protein and the [35 S]GTPγS binding assay and identified novel GPR85 inverse-agonists with IC50 values of approximately 1 µM. To analyze the neurochemical character of the compounds and investigate the physiological significance of GPR85, we used cerebellar Purkinje cells expressing GPR85 and an electrophysiological technique. Based on the results, the inverse-agonist compound for GPR85 modulated potassium channel opening. Together with the results of previous gene analysis of GPR85, we expect that the development of the GPR85 ligand will provide new insights into a few types of neurological disorders.

The Impact of Eribulin on Stathmin Dynamics and Paclitaxel Sensitivity in Ovarian Cancer Cells.

Eribulin, an inhibitor of microtubule dynamics, is used for treating breast cancers and sarcomas. The microtubule-destabilizing protein stathmin may modulate the antiproliferative activity of eribulin on breast cancer cells and leiomyosarcoma cells. The antitumor activity of eribulin in ovarian cancers has not been fully explored, so the present study aimed to determine the antitumor efficacy of eribulin and the involvement of stathmin in ovarian cancers. In a xenograft model of ovarian cancer, eribulin treatment reduced the tumor weight, which was accompanied by an increased level of phosphorylated stathmin. Eribulin stimulated the phosphorylation of stathmin in cultured cancer cell lines. The eribulin-induced phosphorylation of stathmin was inhibited by treatment with FTY720, an activator of protein phosphatase 2A (PP2A), and eribulin downregulated the expression of PP2A subunits. Furthermore, stathmin knockdown abrogated the inhibitory effects of eribulin on cell viability. Eribulin enhanced the antiproliferative effects of paclitaxel and concomitantly decreased stathmin expression. These results suggest that eribulin-induced phosphorylation of stathmin, mediated in part by PP2A downregulation, reduces stathmin activity and enhances the antiproliferative effects of paclitaxel in ovarian cancer. Collectively, the results of this study indicate that eribulin may suppress the proliferation of ovarian cancer cells partly by regulating the activity of stathmin.

Control of structural redundancy from the head to trunk in the human upright standing revealed using a data-driven approach.

The human being dynamically and highly controls the head-trunk with redundant mechanical structures to maintain a stable upright standing position that is inherently unstable. The posture control strategies are also affected by the differences in the conditions of sensory inputs. However, it is unclear how the head-trunk segmental properties are altered to respond to situations that require appropriate changes in standing posture control strategies. We used a data-driven approach to conduct a multipoint measurement of head-trunk sway control in a quiet standing position with differences in the conditions of sensory inputs. Healthy young subjects with 22 accelerometers attached to their backs were evaluated for head-trunk vibration during quiet standing under two conditions: one with open eyes and one with closed eyes. The synchronization of the acceleration and the instantaneous phase was then calculated. The results showed that the synchronization of acceleration and instantaneous phase varied depending on the visual condition, and there were some continuous coherent patterns in each condition. Findings were that the structural redundancy of the head-trunk, which is multi-segmental and has a high mass ratio in the whole body, must be adjusted adaptively according to the conditions to stabilize upright standing in human-specific bipeds.

Minimizing scattering-induced phase errors in differential interference contrast microscopy.

SIGNIFICANCE: Differential interference contrast (DIC) microscopes allow noninvasive in vivo observation of transparent microstructures in tissue without the use of fluorescent dyes or genetic modification. We show how to modify a DIC microscope to measure the sample phase distribution accurately and in real-time even deep inside sample tissue. AIM: Our aim is to improve the DIC microscope's phase measurement to remove the phase bias that occurs in the presence of strong scattering. APPROACH: A quarter-wave plate was added in front of the polarization camera, allowing a modified phase calculation to incorporate all four polarization orientation angles (0 deg, 45 deg, 90 deg, and 135 deg) captured simultaneously by the polarization camera, followed by deconvolution. RESULTS: We confirm that the proposed method reduces phase measurement error in the presence of scattering and demonstrate the method using in vivo imaging of a beating heart inside a medaka egg and the whole-body blood circulation in a young medaka fish. CONCLUSIONS: Modifying a polarization-camera DIC microscope with a quarter-wave plate allows users to image deep inside samples without phase bias due to scattering effects.

Video-rate quantitative phase analysis by a DIC microscope using a polarization camera.

This paper describes how to take advantage of the replacement of an intensity camera with a polarization camera in a standard differential interference contrast (DIC) microscope. Using a polarization camera enables snapshot quantitative phase analysis so that real-time imaging of living transparent tissues become possible. Using our method, we quantify the phase measurement accuracy using a phantom consisting of glass beads embedded in lacquer. In order to demonstrate these advantages, we image the pumping heart and blood flow in a living medaka egg.

Erratum: Video-rate quantitative phase analysis by a DIC microscope using a polarization camera: errata.

[This corrects the article on p. 1273 in vol. 10, PMID: 30891345.].

HVGH: Unsupervised Segmentation for High-Dimensional Time Series Using Deep Neural Compression and Statistical Generative Model.

Humans perceive continuous high-dimensional information by dividing it into meaningful segments, such as words and units of motion. We believe that such unsupervised segmentation is also important for robots to learn topics such as language and motion. To this end, we previously proposed a hierarchical Dirichlet process-Gaussian process-hidden semi-Markov model (HDP-GP-HSMM). However, an important drawback of this model is that it cannot divide high-dimensional time-series data. Furthermore, low-dimensional features must be extracted in advance. Segmentation largely depends on the design of features, and it is difficult to design effective features, especially in the case of high-dimensional data. To overcome this problem, this study proposes a hierarchical Dirichlet process-variational autoencoder-Gaussian process-hidden semi-Markov model (HVGH). The parameters of the proposed HVGH are estimated through a mutual learning loop of the variational autoencoder and our previously proposed HDP-GP-HSMM. Hence, HVGH can extract features from high-dimensional time-series data while simultaneously dividing it into segments in an unsupervised manner. In an experiment, we used various motion-capture data to demonstrate that our proposed model estimates the correct number of classes and more accurate segments than baseline methods. Moreover, we show that the proposed method can learn latent space suitable for segmentation.

Generating action descriptions from statistically integrated representations of human motions and sentences.

It is desirable for robots to be able to linguistically understand human actions during human-robot interactions. Previous research has developed frameworks for encoding human full body motion into model parameters and for classifying motion into specific categories. For full understanding, the motion categories need to be connected to the natural language such that the robots can interpret human motions as linguistic expressions. This paper proposes a novel framework for integrating observation of human motion with that of natural language. This framework consists of two models; the first model statistically learns the relations between motions and their relevant words, and the second statistically learns sentence structures as word n-grams. Integration of these two models allows robots to generate sentences from human motions by searching for words relevant to the motion using the first model and then arranging these words in appropriate order using the second model. This allows making sentences that are the most likely to be generated from the motion. The proposed framework was tested on human full body motion measured by an optical motion capture system. In this, descriptive sentences were manually attached to the motions, and the validity of the system was demonstrated.

Regulation of muscular glutamate metabolism by high-protein diet in broiler chicks.

The major taste active component, glutamate (Glu), improves the taste of meat. In this study, we investigated the effect of a short-term high-protein (HCP) diet on the intramuscular free Glu content to improve the taste of meat. Furthermore, we elucidated how the muscle free Glu content was controlled by the HCP diet. Chicks (14 days old) were fed the control diet or HCP diet for 10 days. Plasma and muscle free amino acid concentrations, and activity and messenger RNA (mRNA) expression of muscle enzymes related to Glu metabolism were determined. Muscle free Glu content was increased (P < 0.01) by 51%. Activity and mRNA expression of glutaminase (GA), which is one of the major Glu-related enzymes, were significantly decreased (P < 0.05) in the HCP group because of feedback inhibition. The mRNA expression of lysine α-ketoglutarate reductase (LKR), which is the enzyme involved in lysine (Lys) degradation and Glu production, was significantly increased (P < 0.001) in the HCP group. These results suggest that short-term dietary HCP feeding is an effective treatment for improving the taste of meat. Furthermore, our results suggest that the free Glu content in muscle is regulated by GA and LKR.