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The gut microbiota can play an important role in enhancing the host’s complex immune system. In this regard, many studies indicate that probiotics consumption has a beneficial impact on alterations in the composition of the gut microbiota. Our previous study demonstrated that the oral administration of Lacticaseibacillus rhamnosus HDB1258 (HDB1258) enhances immune cell activity and alters the composition of gut microbiota in C57BL/6 mice, thereby showing its potential as a novel immunostimulatory ingredient. Therefore, this clinical trial assessed the effects of HDB1258 on human natural killer (NK) cell activity and changes in gut microbiota. It also investigated the correlation between gut microbiota and NK cell activity following HDB1258 supplementation. Participants (n = 71) were randomized into placebo and HDB1258 groups, and NK cell activity and gut microbiota were investigated at baseline (week 0) and endline (week 8). The present study showed that HDB1258 significantly increased NK cell activity and resulted in positive regulatory effects on the gut microbial balance in subjects compared to the placebo group. HDB1258 affected the gut microbial balance by inducing the growth of beneficial bacteria such as Lactococcus and Sutterella. Especially, the changes in Escherichia–Shigella composition were negatively correlated with the changes in NK cell activity after HDB1258 consumption. There was also a positive correlation between the NK cell activity in the HDB1258 group and the composition of Prevotella 9 and Adlercreutzia. These findings suggest that HDB1258 may improve the host’s intestinal environment by regulating gut bacteria related to immune response and promote NK cell activation. This study was registered at clinical research information service (CRIS: KCT0008204).

Methylation-specific (MS) multiplex ligation-dependent probe amplification (MLPA) at two differentially methylated regions (DMRs) at chromosome 11p15, H19-DMR and LIT1-DMR, and microsatellite analysis for uniparental disomy (UPD) at chromosome 7 or 11, have been recommended for the genetic diagnosis of the Beckwith-Wiedemann syndrome (BWS) and the Silver-Russell syndrome (SRS). In this study, the efficacy of the MS pyrosequencing method at H19-DMR and LIT1-DMR at 11p15 and SGCE-DMR at 7q21 was evaluated for the genetic diagnosis of BWS (n=18) and SRS (n=20) patients. Epigenetic alterations or UPD were detected in 83% of BWS and 50% of SRS individuals by MS-MLPA, but the detection rate increased to 95% of BWS and 70% of SRS by MS pyrosequencing. Thirteen BWS patients (72%) harbored loss-of-methylation (LOM) at LIT1-DMR and two patients (11%) harbored gain-of-methylation (GOM) at H19-DMR, whereas two patients (11%) had both LOM at LIT1-DMR and GOM at H19-DMR, reflecting paternal UPD 11. Thirteen SRS patients (65%) harbored LOM at H19-DMR, whereas one patient (5%) had GOM at SGCE-DMR, reflecting maternal UPD 7. Birth anthropometric profiles were significantly correlated to methylation scores at either H19-DMR or LIT1-DMR. In conclusion, MS pyrosequencing enhanced the detection rate of molecular defects in BWS and SRS. Moreover, it indicates that methylation status at 11p15.5 might have an important role in fetal growth.

Because trusting strangers can entail high risk, an ability to infer a potential partner's trustworthiness would be highly advantageous. To date, however, little evidence indicates that humans are able to accurately assess the cooperative intentions of novel partners by using nonverbal signals. In two studies involving human-human and human-robot interactions, we found that accuracy in judging the trustworthiness of novel partners is heightened through exposure to nonverbal cues and identified a specific set of cues that are predictive of economic behavior. Employing the precision offered by robotics technology to model and control humanlike movements, we demonstrated not only that experimental manipulation of the identified cues directly affects perceptions of trustworthiness and subsequent exchange behavior, but also that the human mind will utilize such cues to ascribe social intentions to technological entities.

Fabry disease is an X-linked inborn error of glycosphingolipid catabolism that results from mutations in the gene encoding the α-galactosidase A (GLA) enzyme. We have identified 15 distinct mutations in the GLA gene in 13 unrelated patients with classic Fabry disease and 2 unrelated patients with atypical Fabry disease. Two of the identified mutations were novel (i.e., the D231G missense mutation and the L268delfsX1 deletion mutation). This study evaluated the effects of the chemical chaperones 1-deoxygalactonojirimycin (DGJ) on the function of GLA in vitro , in cells containing missense mutations in the GLA gene. Nine missense and a nonsense mutations, including one novel mutation were cloned into mammalian expression vectors. After transient expression in COS-7 cells, GLA enzyme activity and protein expression were analyzed using fluorescence spectrophotometry and Western blot analysis, respectively. DGJ enhanced GLA enzyme activity in the M42V, I91T, R112C and F113L mutants. Interestingly, the I91T and F113L mutations are associated with the atypical form of Fabry disease. However, DGJ treatment did not have any significant effect on the GLA enzyme activity and protein expression of other mutants, including C142W, D231G, D266N, and S297F. Of note, GLA enzyme activity was not detected in the novel mutant (i.e., D231G), although protein expression was similar to the wild type. In the absence of DGJ, the E66Q mutant had wild-type levels of GLA protein expression and approximately 40% GLA activity, indicating that E66Q is either a mild mutation or a functional single nucleotide polymorphism (SNP). Thus, the results of this study suggest that the chemical chaperone DGJ enhances GLA enzyme activity and protein expression in milder mutations associated with the atypical form of Fabry disease.

Abstract Study Objectives Insomnia Disorder diagnoses require persistent sleep complaints despite “adequate sleep opportunity.” Significant Perinatal Sleep Disruption makes this diagnosis challenging. This longitudinal study distinguished between Insomnia Disorder and Perinatal Sleep Disruption and their sleep and mental health correlates. Methods One hundred sixty-three nulliparous females (age M ± SD = 33.35 ± 3.42) participating in a randomized controlled trial repeated the Insomnia Disorder module of the Duke Structured Interview for Sleep Disorders and Patient-Reported Outcome Measurement Information System measures for sleep and mental health at 30- and 35-weeks’ gestation, and 1.5, 3, 6, 12, and 24 months postpartum (944 interviews, 1009 questionnaires completed). We compared clinical features when Diagnostic and Statistical Manual of Mental Disorders (DSM-5) Insomnia Disorder criteria (without the Duration criterion) were: (1) met (Insomnia Disorder), (2) not met only because of the sleep opportunity criteria (Perinatal Sleep Disruption), and (3) not met due to other criteria (Low Complaint). Results Proportions of Insomnia Disorder were 16.0% and 19.8% during early and late third trimester, and ranged 5.3%–11.7% postpartum. If the sleep opportunity criteria were not considered, rates of Insomnia would be 2–4 times higher (21.4%–40.4%) across time-points. Mixed-effects models adjusting for covariates showed that compared to Low Complaint, both Insomnia Disorder and Perinatal Sleep Disruption scored significantly higher on insomnia and sleep disturbance scales, sleep effort, and sleep-related impairments (p values < .01), but depression and anxiety were comparable (p values > .12). Conclusion Assessing sleep complaints without considering sleep opportunities can result in over-diagnosis of Insomnia Disorder in the perinatal periods. Insomnia Disorder and Perinatal Sleep Disruption were both associated with adverse sleep and mood outcomes, and need to be carefully differentiated and appropriately addressed. Clinical Trial Registration: The SEED Project (Sleep, Eat, Emotions, and Development): A randomized controlled pilot study of a perinatal sleep intervention on sleep and wellbeing in mothers and infants. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371634, Australian New Zealand Clinical Trials Registry: ACTRN12616001462471.

Oncogenic H-Ras G12V and its variants have been shown to inhibit muscle differentiation. However, the role of proto-oncogenic Ras （c-Ras） in muscle differentiation remains unclear. The active GTP-bound form of Ras has been known to associate with diverse effectors including Raf, phosphatidylinositol 3-kinase （PI3K）, RaI-GDS, and other molecules to transmit downstream signals. We hypothesize that c-Ras may stimulate muscle differentiation by selectively activating PI3K, an important mediator for muscle differentiation. In our experiments, inhibition of c-Ras by farnesyltransferase inhibitors and a dominant negative form of H-Ras （Ras S17N） suppressed muscle differentiation. Consistently, individual knockdown of H-Ras, K-Ras, and N-Ras by siRNAs all blocked muscle differentiation. Interestingly, we found that c-Ras preferentially interacts with PI3K rather than its major binding partner c-Raf, during myogenic differentiation, with total c-Ras activity remaining unchanged. PI3K and its downstream myogenic pathway, the Nox2/NF-kB/inducible nitric oxide synthase （iNOS） pathway, were found to be suppressed by inhibition of c-Ras activity during differentiation. Furthermore, expression of a constitutively active form of PI3K completely rescued the differentiation block and reactivated the Nox2/NF-kB/iNOS pathway in c-Ras-inhibited cells. On the ba- sis of our results, we conclude that contrary to oncogenic Ras, proto-oncogenic H-Ras, K-Ras, and N-Ras are directly involved in the promotion of muscle differentiation via PI3K and its downstream signaling pathways. In addition, PI3K pathway activation is associated with a concurrent suppression of the otherwise predominantly activated Raf/ Mek/Erk pathway.

The CO2 concentrations and fluxes over an urban forest site （Namsan） and an urban residential region （Boramae） in Seoul, Korea, during the non-growing season （2 4 March 2011）, the growing season （10-12 June 2011）, and the late-growing season （22-24 September 2011） were analyzed. The CO2 concentrations of two sites showed nearly the same diurnal variation, with a maximum value occurring during the night and a minimum value occurring during daytime, as well as the same seasonal variation, with a maximum value during the non-growing season （early spring） and a minimum value during the growing season （summer）. The CO2 flux over the urban forest did not show any typical diurnal variation during the non-growing season, but did show diurnal variation with a small positive value during the night and a large negative value during daytime in the growing and late-growing seasons due to photosynthesis in the urban forest. The CO2 flux over the urban residential region showed a positive daily mean value for all periods, with large values during the non-growing season and small values during the growing season, and it also showed diurnal variation with two maxima at 0600-1000 LST and 1800-2400 LST, and two minima at 0300-0600 LST and 1100-1500 LST, and was strongly correlated with the use of liquefied natural gas for cooking and heating by surrounding houses.

We describe the design, implementation, and validation of a computational model for recognizing interpersonal trust in social interactions. We begin by leverage pre-existing datasets to understand the relationship between synchronous movement, mimicry, and gestural cues with trust. We found that although synchronous movement was not predictive of trust, synchronous movement is positively correlated with mimicry. That is, people who mimicked each other more frequently also move more synchronously in time together. And revealing the versatile nature of unconscious mimicry, we found mimicry to be predictive of liking between participants instead of trust. We reconfirmed that the following four negative gestural cues, leaning-backward, face-touching, hand-touching, and crossing-arms, when taken together are predictive of lower levels of trust, while the following three positive gestural cues, leaning-forward, having arms-in-lap, and open-arms, were predictive of higher levels of trust. We train and validate a probabilistic graphical model using natural social interaction data from 74 participants. And by observing how these seven important gestures unfold throughout the social interaction, our Trust Hidden Markov Model is able to predict with 94% accuracy whether an individual is willing to behave cooperatively or uncooperatively with their novel partner. And by simulating the resulting model, we found that not only does the frequency in the emission of the predictive gestures matter as well, but also the sequence in which we emit negative to positive cues matter. We attempt to automate this recognition process by detecting those trust-related behaviors through 3D motion capture technology and gesture recognition algorithms. And finally, we test how accurately our entire system, with low-level gesture recognition for high-level trust recognition, can predict whether an individual finds another to be trustworthy or untrustworthy.

Fabry disease is an X-linked inborn error of glycosphingolipid catabolism that results from mutations in the gene encoding the α-galactosidase A (GLA) enzyme. We have identified 15 distinct mutations in the GLA gene in 13 unrelated patients with classic Fabry disease and 2 unrelated patients with atypical Fabry disease. Two of the identified mutations were novel (i.e., the D231G missense mutation and the L268delfsX1 deletion mutation). This study evaluated the effects of the chemical chaperones 1-deoxygalactonojirimycin (DGJ) on the function of GLA in vitro, in cells containing missense mutations in the GLA gene. Nine missense and a nonsense mutations, including one novel mutation were cloned into mammalian expression vectors. After transient expression in COS-7 cells, GLA enzyme activity and protein expression were analyzed using fluorescence spectrophotometry and Western blot analysis, respectively. DGJ enhanced GLA enzyme activity in the M42V, I91T, R112C and F113L mutants. Interestingly, the I91T and F113L mutations are associated with the atypical form of Fabry disease. However, DGJ treatment did not have any significant effect on the GLA enzyme activity and protein expression of other mutants, including C142W, D231G, D266N, and S297F. Of note, GLA enzyme activity was not detected in the novel mutant (i.e., D231G), although protein expression was similar to the wild type. In the absence of DGJ, the E66Q mutant had wild-type levels of GLA protein expression and approximately 40% GLA activity, indicating that E66Q is either a mild mutation or a functional single nucleotide polymorphism (SNP). Thus, the results of this study suggest that the chemical chaperone DGJ enhances GLA enzyme activity and protein expression in milder mutations associated with the atypical form of Fabry disease.

This study was intended to provide basic data for discussion on the introduction of safety and health education system for business owners to prevent industrial accidents. To this end, a questionnaire survey was conducted on 548 occupational safety and health officials, of which 86.7% expected that the introduction of safety and health education for business owners would be very helpful in preventing accidents in the workplace. On the other hand, it was pointed out that the effectiveness of safety and health education for business owners needs to be raised as it deals with the areas considered to be important in the job and basic competencies of business owners. The study subjects also most highly agreed with the need for annual regular training for business owners at all workplaces.