Deep learning-based sleep stage classification with cardiorespiratory and body movement activities in individuals with suspected sleep disorders.

Deep learning methods have gained significant attention in sleep science. This study aimed to assess the performance of a deep learning-based sleep stage classification model constructed using fewer physiological parameters derived from cardiorespiratory and body movement data. Overnight polysomnography (PSG) data from 123 participants (age: 19-82 years) with suspected sleep disorders were analyzed. Multivariate time series data, including heart rate, respiratory rate, cardiorespiratory coupling, and body movement frequency, were input into a bidirectional long short-term memory (biLSTM) network model to train and predict five-class sleep stages. The trained model's performance was evaluated using balanced accuracy, Cohen's κ coefficient, and F1 scores on an epoch-per-epoch basis and compared with the ground truth using the leave-one-out cross-validation scheme. The model achieved an accuracy of 71.2 ± 5.8%, Cohen's κ of 0.425 ± 0.115, and an F1 score of 0.650 ± 0.083 across all sleep stages, and all metrics were negatively correlated with the apnea-hypopnea index, as well as age, but positively correlated with sleep efficiency. Moreover, the model performance varied for each sleep stage, with the highest F1 score observed for N2 and the lowest for N3. Regression and Bland-Altman analyses between sleep parameters of interest derived from deep learning and PSG showed substantial correlations (r = 0.33-0.60) with low bias. The findings demonstrate the efficacy of the biLSTM deep learning model in accurately classifying sleep stages and in estimating sleep parameters for sleep structure analysis using a reduced set of physiological parameters. The current model without using EEG information may expand the application of unobtrusive in-home monitoring to clinically assess the prevalence of sleep disorders outside of a sleep laboratory.

A monoacylglyceryltrimethylhomoserine, 21F121-A, containing a branched acyl group from Penicillium glaucoroseum.

A new monoacylglyceryltrimethylhomoserine, 21F121-A (1), was isolated from the culture of Penicillium glaucoroseum (21F00121) by LCMS-guided purification. The structure was elucidated by NMR and mass spectrometries. The absolute configuration of the homoserine moiety was analyzed by the ECD spectrum after acid hydrolysis, and the S-configuration of the glycerol moiety was determined based on the spectrum of the 1,2-dibenzoyl derivative after acid hydrolysis. Although a variety of diacylglyceryltrimethylhomoserine is distributed in lower plants and fungi, a limited number of studies on monoacyl derivatives have been reported. This is the fourth sample of monoacylglyceryltrimethylhomoserine discovered from a natural source, and the second sample isolated from a fungus. Compound 1 contains an unusual branched pentaene chain attached at the sn-1 position of glycerol and weakly inhibited the growth of HCT116 cells.

Colletofragarone A2 Inhibits Cancer Cell Growth In Vivo and Leads to the Degradation and Aggregation of Mutant p53.

Mutant p53 not only loses its original tumor suppressor function but also acquires new abilities regarding oncogenic progression. Therefore, the strategy of targeting mutant p53 has attracted attention for cancer therapy. We isolated colletofragarone A2 (CF) from the fungus Colletotrichum sp. (13S020), which decreases mutant p53 levels in cells, and herein examine its effect on mutant p53. CF showed more potent cytotoxic activities on cells with p53R175H structural mutants than those with different p53 statuses such as a DNA-contact mutant, wild-type, and null cells. CF markedly decreased tumor cell growth in vivo using a mouse xenograft model with HuCCT1 (p53R175H) cells. Cotreatment of SK-BR-3 (p53R175H) cells with CF and cycloheximide decreased mutant p53 levels by promoting p53 degradation. In the presence of MG-132, CF induced the accumulation of the aggregated mutant p53. These results suggest that CF inhibits the function of molecular chaperones such as HSP90.

Formation of glyco-functionalized interfaces for protein binding using polyphenolic glycoside.

In this study, a polyphenolic glycoside (α-glucosyl rutin) was used to form glyco-functionalized interfaces for protein binding. α-Glucosyl rutin was coated onto precious metals, metal oxides, and synthetic polymers, including polyethylene and polytetrafluoroethylene with poor surface modifiability. The glyco-functionalized interfaces bound strongly and specifically to concanavalin A and Bauhinia purpurea lectin, which have different carbohydrate specificities. Competitive adsorption tests demonstrated that the binding sites for the abovementioned lectins were glucosyl and rhamnosyl residues, respectively. The glyco-functionalized interfaces maintained the protein binding ability after being stored in aqueous solution for 1 day and in air for 160 days. Once the glyco-functionalized interfaces were formed on gold, silicon dioxide, polystyrene, and polytetrafluoroethylene using α-glucosyl rutin, all the glyco-functionalized interfaces bound to concanavalin A rather than peanut agglutinin.

The pilot study of a Neuropsychological Educational Approach to Cognitive Remediation for patients with schizophrenia in Japan.

The main aim of this study is to demonstrate the feasibility and efficacy of a Neuropsychological Educational Approach to Cognitive Remediation (NEAR) in Japan. This multi-site study used a quasi-experimental design. Fifty-one patients with schizophrenia or schizoaffective disorder participated. The NEAR program consisted of two 1-h computer sessions per week and an additional group meeting session lasting 30 to 60 min once a week. The subjects completed 6 months of NEAR sessions before being assessed. Moreover, taking into consideration the possible practice effect, we assessed 21 control patients twice with an interval of 6 months. We assessed cognitive function by using the Japanese version of the Brief Assessment of Cognition in Schizophrenia (BACS-J). Consequently, the NEAR group showed significant improvement in overall cognitive function, and in comparison with the control group, these findings were generally similar except for motor speed. Although the present study has its limitations, it demonstrates that the NEAR is feasible in Japan as well as it is in Western countries.

A balanced diet is necessary for proper entrainment signals of the mouse liver clock.

BACKGROUND: The peripheral circadian clock in mice is entrained not only by light-dark cycles but also by daily restricted feeding schedules. Behavioral and cell culture experiments suggest an increase in glucose level as a factor in such feeding-induced entrainment. For application of feeding-induced entrainment in humans, nutrient content and dietary variations should be considered. PRINCIPAL FINDING: To elucidate the food composition necessary for dietary entrainment, we examined whether complete or partial substitution of dietary nutrients affected phase shifts in liver clocks of mice. Compared with fasting mice or ad libitum fed mice, the liver bioluminescence rhythm advanced by 3-4 h on the middle day in Per2::luciferase knock-in mice that were administered a standard mouse diet, i.e. AIN-93M formula [0.6-0.85 g/10 g mouse BW] (composition: 14% casein, 47% cornstarch, 15% gelatinized cornstarch, 10% sugar, 4% soybean oil, and 10% other [fiber, vitamins, minerals, etc.]), for 2 days. When each nutrient was tested alone (100% nutrient), an insignificant weak phase advance was found to be induced by cornstarch and soybean oil, but almost no phase advance was induced by gelatinized cornstarch, high-amylose cornstarch, glucose, sucrose, or casein. A combination of glucose and casein without oil, vitamin, or fiber caused a significant phase advance. When cornstarch in AIN-93M was substituted with glucose, sucrose, fructose, polydextrose, high-amylose cornstarch, or gelatinized cornstarch, the amplitude of phase advance paralleled the increase in blood glucose concentration. CONCLUSIONS: Our results strongly suggest the following: (1) balanced diets containing carbohydrates/sugars and proteins are good for restricted feeding-induced entrainment of the peripheral circadian clock and (2) a balanced diet that increases blood glucose, but not by sugar alone, is suitable for entrainment. These findings may assist in the development of dietary recommendations for on-board meals served to air travelers and shift workers to reduce jet lag-like symptoms.

Dynamic gene expression of Lin-28 during embryonic development in mouse and chicken.

The Caenorhabditis elegans heterochronic gene lin-28 regulates developmental timing in the nematode trunk. We report the dynamic expression patterns of Lin-28 homologues in mouse and chick embryos. Whole mount in situ hybridization revealed specific and intriguing expression patterns of Lin-28 in the developing mouse and chick limb bud. Mouse Lin-28 expression was detected in both the forelimb and hindlimb at E9.5, but disappeared from the forelimb at E10.5, and finally from the forelimb and hindlimb at E11.5. Chicken Lin-28, which was first detected in the limb primordium at stage 15/16, was also downregulated as the stage proceeded. The amino acid sequences of mouse and chicken Lin-28 genes are highly conserved and the similar expression patterns of Lin-28 during limb development in mouse and chicken suggest that this heterochronic gene is also conserved during vertebrate limb development.

Zeta-sarcoglycan is a functional homologue of gamma-sarcoglycan in the formation of the sarcoglycan complex.

The sarcoglycans (SGs), transmembrane components of the dystrophin-associated glycoprotein complex, are stable and functional only when they assemble into a tetrameric complex in muscle cells. A defect in any one of the four SG members disrupts the entire SG complex (SGC) and causes limb-girdle muscular dystrophy. zeta-SG has been recently found as a transmembrane protein homologous to gamma-SG and delta-SG. To characterize zeta-SG in complex formation, we co-transfected expression vectors encoding all six SGs (alpha-, beta-, gamma-, delta-, epsilon- and zeta-SG) and dystroglycan into Chinese hamster ovary cells. Immunoprecipitation analysis showed that zeta-SG or gamma-SG formed a SGC with beta-SG and delta-SG plus alpha-SG or epsilon-SG, revealing that zeta-SG can form two types of SGCs (alpha-beta-zeta-delta or epsilon-beta-zeta-delta). This result indicates the functional resemblance of zeta-SG to gamma-SG rather than delta-SG, although phylogenetic analysis suggests that zeta-SG is evolutionally closer to delta-SG than to gamma-SG. Reverse transcription (RT)-PCR showed that the expression pattern of the transcript was almost the reciprocal of that of gamma-SG in various mouse tissues and that the zeta-SG transcript was especially abundant in the brain, suggesting that zeta-SG might play a particular role in the central nervous system.

Immunohistochemical localization of gastrin-releasing peptide receptor in the mouse brain.

Gastrin-releasing peptide (GRP) is a mammalian bombesin (BN)-like peptide that binds with high affinity to the GRP receptor (GRP-R). Previous behavioral studies using mice and rats showed that the GRP/GRP-R system mediates learning and memory by modulating neurotransmitter release in the local GABAergic network of the amygdala and the nucleus tractus solitarius (NTS). To date, the precise distribution of GRP-R in the brain has not been elucidated. We used a synthetic peptide derived from mouse GRP-R to generate affinity-purified antibodies to GRP-R and used immunohistochemistry to determine the distribution of GRP-R in the mouse brain. The specificity of anti-GRP-R antibody was confirmed in vitro using COS-7 cells transiently expressing GRP-R and in vivo using GRP-R-deficient and wild-type mouse brain sections. GRP-R immunoreactivity was widely distributed in the isocortex, hippocampal formation, piriform cortex, amygdala, hypothalamus, and brain stem. In particular, GRP-R immunoreactivity was observed in the lateral (LA), central, and basolateral amygdaloid (BLA) nuclei and NTS, which are important regions for memory performance. Double-labeling immunohistochemistry demonstrated that subpopulations of GRP-R are present in GABAergic neurons in the amygdala. Consequently, GRP-R immunoreactivity was observed in the GABAergic neurons of the limbic region. These anatomical results provide support for the idea that the GRP/GRP-R system mediates memory performance by modulating neurotransmitter release in the local GABAergic network.

Comparison of mice deficient in the high- or low-affinity neurotensin receptors, Ntsr1 or Ntsr2, reveals a novel function for Ntsr2 in thermal nociception.

Neurotensin (NT) is a neuropeptide that induces a wide range of biological activities including hypothermia and analgesia. Such effects are mediated by the NT receptors Ntsr1, Ntsr2 and Ntsr3, although the involvement of each receptor in specific NT functions remains unknown. To address nociceptive function in vivo, we generated both Ntsr1-deficient and Ntsr2-deficient mice. In addition, histochemical analyses of both Ntsr1 and Ntsr2 mRNAs were performed in the mouse brain regions involved in NT-related nociception. The expression of Ntsr2 mRNA was greater than that of Ntsr1 in the periaqueductal gray (PAG) and the rostral ventral medulla (RVM). The mutant and control mice were subjected to the examination of thermal nociception, and in the hot plate test, a significant alteration in jump latency was observed in Ntsr2-deficient mice compared to Ntsr1-deficient or wild-type control mice. Latencies of tail flick and hind paw licking of the mutant mice were not affected compared to control mice. These results suggest that Ntsr2 has an important role in thermal nociception compared to Ntsr1, and that these mutant mice may represent a useful tool for the development of analgesic drugs.

Ubiquitin carboxy-terminal hydrolase L1 binds to and stabilizes monoubiquitin in neuron.

Mammalian neuronal cells abundantly express a deubiquitylating enzyme, ubiquitin carboxy-terminal hydrolase 1 (UCH L1). Mutations in UCH L1 are linked to Parkinson's disease as well as gracile axonal dystrophy (gad) in mice. In contrast to the UCH L3 isozyme that is universally expressed in all tissues, UCH L1 is expressed exclusively in neurons and testis/ovary. We found that UCH L1 associates and colocalizes with monoubiquitin and elongates ubiquitin half-life. The gad mouse, in which the function of UCH L1 is lost, exhibited a reduced level of monoubiquitin in neurons. In contrast, overexpression of UCH L1 caused an increase in the level of ubiquitin in both cultured cells and mice. These data suggest that UCH L1, with avidity and affinity for ubiquitin, insures ubiquitin stability within neurons. This study is the first to show the function of UCH L1 in vivo.

Developmental Change in Microheterogeneity of Serum Transferrin of Chickens: (developmental change/microheterogeneity/transferrin/chicken serum).

Developmental change in microheterogeneity of chicken serum transferrin (Tf) was investigated by polyacrylsmide-gel isoelectric focusing, direct immunofixation, and densitometry. Three main Tf species (Tf-0, Tf-1, and Tf-2, which have 0, 1, and 2 sialic acid residues per molecule, respectively) were resolved and their relative ratios were determined. As development proceeded, a relative increase occurred in the most acidic species (Tf-2) with decreases in the less acidic ones (Tf-0 and Tf-1).

Further Studies on the Developmental Change in Myotrophic Activity of Chicken Serum: Relation between Activity and Transferrin: (developmental change/myotrophic activity/chicken serum/transferrin).

As an extension of previous studies, we reexamined the developmental change in trophic activity of chicken serum on chicken myogenic cells in vitro and attempted to elucidate it on the basis of possible changes in serum transferrin (Tf), the myotrophic activity of which depends both on its concentration and on the level of its iron-saturation. The myotrophic activity was found to be low until the second week in ovo, then to increase rather abruptly to a plateau at about the time of hatching, and then to decrease to the adult level. Determination of the concentration and level of iron-saturation of serum Tf suggested that the change in myotrophic activity was mainly caused by these two parameters, though another factor(s) may also be involved.

Indispensability of Iron-bound Chick Transferrin for Chick Myogenesis in Vitro: (myogenesis/transfrrin/iron).

Myotrophic activity of highly purified chick transferrins (Tfs) to chick primary myogenic cells has been studied in a culture medium containing horse serum. Iron-binding to Tfs is indispensable for the activity. The removal of iron from Tfs gives rise to a complete loss of the activity and it is restored by iron-rebinding depending on the amount of bound iron. This result, combined with other physicochemical and immunological data, strongly, confirms that the myotrophic activity is exerted by the Tfs themselves, not by a contaminating material(s). It has been found that culture medium containing horse Tf which seems inadequate for the study of the biological effects of Tfs is, however, suitable for studies on chick Tfs, since horse Tf is inactive in promoting chick myogenesis. Terminal sialic acid residues are unrelated to myotrophic activity since Tfs with different numbers of residues (0, 1, and 2 moles/Tf molecule) are comprable in their activities. The mechanism of Tf action on cells and contradictions among previous papers as to the requirement of Tf for cell growth have been discussed from the viewpoint of an iron-donor with class-specificity.

Chick Embryo Extract, Muscle Trophic Factor and Chick and Horse Sera as Environments for Chick Myogenic Cell Growth.

Chick myogenic cells grew in a medium composed of Eagle's minimum essential medium (MEM), horse serum (HS), and one of the essential factors needed for myogenic cell growth (EFMG), that is, chick embryo extract (EE), chick serum (CS), or the muscle trophic factor (MTF). But they did not grow in the absence of the EFMG. In the absence of HS, they scarcely grew in a medium composed of MEM, and EE or MTF. They grew in a medium composed of MEM and CS; they grew much better in a medium composed of MEM, CS, and HS. In the presence of one of the EFMG, the optimal HS concentration for growth varied depending on its lot. At higher HS concentrations, growth was suppressed. Further, it was suggested that an inhibitory substance(s) for myogenic cell growth was present in HS. The inhibitory effects can usually be minimized by diluting the serum with an artificial medium.