Bifidobacterium adolescentis SBT2786 Improves Sleep Quality in Japanese Adults with Relatively High Levels of Stress: A Randomized, Double-Blind, Placebo-Controlled Study.

Sleep disorders associated with lifestyle changes and unhealthy habits are major public health concerns. Our previous study showed that Bifidobacterium adolescentis SBT2786 has a potent sleep-promoting effect on fruit flies. Fruit flies share many similarities with mammals, making them suitable model organisms for studying sleep. Thus, in the present study, we conducted a randomized, double-blind, placebo-controlled clinical trial to test whether SBT2786 has sleep-enhancing effects in humans. In this study, 61 participants in the SBT2786 group and 65 participants in the placebo group were analyzed. The results showed that SBT2786 increased sleep time; however, it predominantly increased light sleep and did not improve subjective sleep quality. Interestingly, mood improvement was observed. A subgroup analysis was conducted on participants with high stress levels, and results showed that these participants experienced an increase in sleep duration and an improvement in sleepiness upon waking up and reported feeling well-rested during the day. We concluded that SBT2786 may improve sleep quality, particularly in individuals experiencing high levels of stress, and that SBT2786 can be used as a dietary supplement to improve sleep and mood.

Mechanism for High-Precision Control of Movement at Maximum Output in the Vertical Jump Task.

Human movements are governed by a tradeoff between speed and accuracy. Previous studies that have investigated the tradeoff relationship in sports movements involving whole-body movements have been limited to examining the relationship from the perspective of competition-specific movements, and the findings on whether the relationship is valid have not been unified. Therefore, this study incorporated a vertical jump task with the introduction of a condition in which landing position control was added to evaluate the essence of a sports movement that requires both speed and accuracy. Accuracy was examined using a method that quantifies the coordinates of the landing and takeoff positions using entropy. The mechanism of that tradeoff was then examined by confirming the phenomenon and analyzing the 3D vector trajectories. An increase in accuracy and a decrease in speed were observed when the landing position was the control target, even in the vertical jumping task normally performed at maximum effort, and the 3D velocity vector was characterized by the following: a reduced scalar and a more vertical direction. While the entropy from the takeoff to the landing position seemed to decrease when the accuracy of the landing position improved, the following noteworthy results were obtained given the characteristics of the vertical jump. Unlike traditional feedback control in the entropy reduction in hand movements, the trajectory is predetermined in a feedforward-like manner by controlling the initial velocity vector at takeoff, which allows the landing point to be adjusted.

Human Information Processing of the Speed of Various Movements Estimated Based on Trajectory Change.

Fitts' approach, which examines the information processing of the human motor system, has the problem that the movement speed is controlled by the difficulty index of the task, which the participant uniquely sets, but it is an arbitrary speed. This study rigorously aims to examine the relationship between movement speed and information processing using Woodworth's method to control movement speed. Furthermore, we examined movement information processing using an approach that calculates probability-based information entropy and mutual information quantity between points from trajectory analysis. Overall, 17 experimental conditions were applied, 16 being externally controlled and one being self-paced with maximum speed. Considering that information processing occurs when irregularities decrease, the point at which information processing occurs switches at a movement frequency of approximately 3.0-3.25 Hz. Previous findings have suggested that motor control switches with increasing movement speed; thus, our approach helps explore human information processing in detail. Note that the characteristics of information processing in movement speed changes that were identified in this study were derived from one participant, but they are important characteristics of human motor control.

Behavioral screening of sleep-promoting effects of human intestinal and food-associated bacteria on Drosophila melanogaster.

Commensal microbes influence various aspects of vertebrate and invertebrate brain function. We previously reported that Lactiplantibacillus plantarum SBT2227 promotes sleep in the fruit fly, Drosophila melanogaster. However, how widely the sleep-promoting effects are conserved in gut bacterial species remains unknown. In this study, we orally administered human intestinal and food-associated bacterial species (39 in total) to flies and investigated their effects on sleep. Six species of bacteria were found to have significant sleep-promoting effects. Of these, we further investigated Bifidobacterium adolescentis, which had the greatest sleep-promoting effect, and found that the strength of the sleep effect varied among strains of the same bacterial species. The B. adolescentis strains BA2786 and BA003 showed strong and weak effects on sleep, respectively. Transcriptome characteristics compared between the heads of flies treated with BA2786 or BA003 revealed that the gene expression of the insulin-like receptor (InR) was increased in BA2786-fed flies. Furthermore, a heterozygous mutation in InR suppressed the sleep-promoting effect of BA2786. These results suggest that orally administered sleep-promoting bacteria (at least BA2786), may act on insulin signaling to modulate brain function for sleep.

Assessment of horizontal gene transfer-mediated destabilization of Synechococcus elongatus PCC 7942 biocontainment system.

Biological containment is a biosafety strategy that prevents the dispersal of genetically modified organisms in natural ecosystems. We previously established a biocontainment system that makes bacterial growth dependent on the availability of phosphite (Pt), an ecologically rare form of phosphorus (P), by introducing Pt metabolic pathway genes and disrupting endogenous phosphate and organic phosphate transporter genes. Although this system proved highly effective, horizontal gene transfer (HGT) mediated recovery of a P transporter gene is considered as a potential pathway to abolish the Pt-dependent growth, resulting in escape from the containment. Here, we assessed the risk of HGT driven escape using the Pt-dependent cyanobacterium Synechococcus elongatus PCC 7942. Transformation experiments revealed that the Pt-dependent strain could regain phosphate transporter genes from the S. elongatus PCC 7942 wild-type genome and from the genome of the closely related strain, S. elongatus UTEX 2973. Transformed S. elongatus PCC 7942 became viable in a phosphate-containing medium. Meanwhile, transformation of the Synechocystis sp. PCC 6803 genome or environmental DNA did not yield escape strains, suggesting that only genetic material derived from phylogenetically-close species confer high risk to generate escape. Eliminating a single gene necessary for natural competence from the Pt-dependent strain reduced the escape occurrence rate. These results demonstrate that natural competence could be a potential risk to destabilize Pt-dependence, and therefore inhibiting exogenous DNA uptake would be effective for enhancing the robustness of the gene disruption-dependent biocontainment.

Gatekeeper Residue Replacement in a Phosphite Transporter Enhances Mutational Robustness of the Biocontainment Strategy.

Biocontainment is a key methodology to reduce environmental risk through the deliberate release of genetically modified microorganisms. Previously, we developed a phosphite (HPO32-)-dependent biocontainment strategy, by expressing a phosphite-specific transporter HtxBCDE and phosphite dehydrogenase in bacteria devoid of their indigenous phosphate (HPO42-) transporters. This strategy did not allow Escherichia coli to generate escape mutants (EMs) in growth media containing phosphate as a phosphorus source using an assay with a detection limit of 1.9 × 10-13. In this study, we found that the coexistence of a high dose of phosphate (>0.5 mM) with phosphite in the growth medium allows the phosphite-dependent E. coli strain to generate EMs at a frequency of approximately 5.4 × 10-10. In all EMs, the mutation was a single amino acid substitution of phenylalanine to cysteine or serine at position 210 of HtxC, the transmembrane domain protein of the phosphorus compound transporter HtxBCDE. Replacement of the HtxC F210 residue with the other 17 amino acids revealed that HtxC F210 is crucial in determining substrate specificity of HtxBCDE. Based on the finding of the role of HtxC F210 as a "gatekeeper" residue for this transporter, we demonstrate that the replacement of HtxC F210 with amino acids resulting from codons that require two simultaneous point mutations to generate phosphate permissive HtxC mutants can reduce the rate of EM generation to an undetectable level. These findings also provide novel insights into the functional classification of HtxBCDE as a noncanonical ATP-binding cassette transporter in which the transmembrane domain protein participates in substrate recognition.

Biogenic action of Lactobacillus plantarum SBT2227 promotes sleep in Drosophila melanogaster.

Lactic acid bacteria (LAB) influence multiple aspects of host brain function via the production of active metabolites in the gut, which is known as the pre/probiotic action. However, little is known about the biogenic effects of LAB on host brain function. Here, we reported that the Lactobacillus plantarum SBT2227 promoted sleep in Drosophila melanogaster. Administration of SBT2227 primarily increased the amount of sleep and decreased sleep latency at the beginning of night-time. The sleep-promoting effects of SBT2227 were independent of the existing gut flora. Furthermore, heat treatment or mechanical crushing of SBT2227 did not suppress the sleep-promoting effects, indicative of biogenic action. Transcriptome analysis and RNAi mini-screening for gut-derived peptide hormones revealed the requirement of neuropeptide F, a homolog of the mammalian neuropeptide Y, for the action of SBT2227. These biogenic effects of SBT2227 on the host sleep provide new insights into the interaction between the brain and gut bacteria.

Estimating Information Processing of Human Fast Continuous Tapping from Trajectories.

Fitts studied the problem of information capacity and transfer in the speed-accuracy motor paradigm using a theoretical approach developed from Shannon and Weaver's information theory. The information processing (bit/s) estimated in Fitts' study is calculated from the movement time required to achieve the required task index of difficulty but is essentially different from Shannon's information entropy. Thus, we estimated the information entropy of multiple human movement trajectories and the mutual information among trajectories for the continuous aiming task in Fitts' paradigm. Further, we estimated the information processing moment by moment. Two methods were considered: (1) encoded values encompassing the coordinates of the three dimensions and (2) coordinate values associated with each direction in the three dimensions. Information entropy indicates the magnitude of variation at each time point, and the structure of this variation varies with the index of difficulty. The ratio of entropy to mutual information was examined, and it was found that information was processed from the first half of the trajectory in difficult tasks. In addition, since these values calculated from the encoded method were higher than those from the conventional method, this method may be able to estimate these values successfully.

Enantioselective Synthesis of Oxazaborolidines by Palladium-Catalyzed N-H/B-H Double Activation of 1,2-Azaborines.

A palladium-catalyzed N-H/B-H double activation of 1,2-dihydro-1,2-benzazaborines proceeded via cycloaddition with vinyl ethylene carbonate to produce polycyclic oxazaborolidines in 31-96 % yield. The key step in this process is the release of molecular hydrogen from a borate intermediate. Using a SPINOL-derived phosphoramidite as a chiral ligand, chiral oxazaborolidines were synthesized in good to high yields with excellent enantioselectivity (up to 95 % ee). The vinyl group of the resulting oxazaborolidine underwent metathesis, Heck reaction, and Wacker oxidation without affecting the oxazaborolidine framework.

Effects of interactions between facial expressions and self-focused attention on emotion.

Self-focus is a type of cognitive processing that maintains negative emotions. Moreover, bodily feedback is also essential for maintaining emotions. This study investigated the effect of interactions between self-focused attention and facial expressions on emotions. The results indicated that control facial expression manipulation after self-focus reduced happiness scores. On the contrary, the smiling facial expression manipulation after self-focus increased happiness scores marginally. However, facial expressions did not affect positive emotions after the other-focus manipulation. These findings suggest that self-focus plays a pivotal role in facial expressions' effect on positive emotions. However, self-focusing is insufficient for decreasing positive emotions, and the interaction between self-focus and facial expressions is crucial for developing positive emotions.

Paradoxical somatic information processing for interoception and anxiety in alexithymia.

The concept of alexithymia has garnered much attention in an attempt to understand the psychological mechanisms underlying the experience of feeling an emotion. In this study, we aimed to understand how the interoceptive processing in an emotional context relates to problems of alexithymia in recognizing self-emotions. Therefore, we prepared experimental conditions to induce emotional awareness based on interoceptive information. As such, we asked participants to be aware of interoception under an anxiety-generating situation anticipating pain, having them evaluate their subjective anxiety levels in this context. High alexithymia participants showed attenuated functional connectivity within their 'interoception network', particularly between the insula and the somatosensory areas when they focused on interoception. In contrast, they had enhanced functional connectivity between these regions when they focused on their anxiety about pain. Although access to somatic information is supposed to be more strongly activated while attending to interoception in the context of primary sensory processing, high alexithymia individuals were biased as this process was activated when they felt emotions, suggesting they recognize primitive and unprocessed bodily sensations as emotions. The paradoxical somatic information processing may reflect their brain function pathology for feeling emotions and their difficulty with context-dependent emotional control.

Fitts' law when errors are not allowed: Quantification of reciprocating trajectories and estimating information processing.

There are circumstances in which humans are required to move in environments wherein accuracy should be maximized, such as golf putting or surgeons' hand movements during surgical procedures. Fitts' law expresses human movement by movement time and task difficulty, which is determined by one's distance from the target and the targets' size. Additionally, this law is considered as the most universal expression of human movement. However, it is calculated based on the possibility of failure, mainly because a tap error ratio of ~4% occurred in the continuous tap task used by Fitts. Thus, this study aimed to examine how movement changes can occur with an error rate of 0%, and whether Fitts' law can be applied to human movement in such a setting. The continuous tap task was performed under two conditions: a conventional one, and a new condition where the devised error rate becomes 0%. To measure movement change during tapping, the variation of the entire trajectory was quantified by principal component analysis, and changes in the quantified values of the trajectory toward the target were examined. For the new condition, no tapping errors occurred; the quantified value of the trajectory toward the target decreased compared with the conventional condition. It was considered that this related to the process of feedback control, and that this process related to an increase in movement time per tap. We suggest that increased information processing may account for these changes. Furthermore, the Fitts' law model, shown from the regression lines for movement time and difficulty, displayed a high fit for both conditions. However, it was difficult to evaluate movement time with the highest index of difficulty for the new condition using the model for the conventional condition. Therefore, we conclude that the conventional model may need to be modified for conditions where the error rate is 0%.

Phosphite Reduces the Predation Impact of Poterioochromonasmalhamensis on Cyanobacterial Culture.

Contamination by the predatory zooplankton Poterioochromonas malhamensis is one of the major threats that causes catastrophic damage to commercial-scale microalgal cultivation. However, knowledge of how to manage predator contamination is limited. Previously, we established a phosphite (Pt)-based culture system by engineering Synechococcus elongatus, which exerted a competitive growth advantage against microbial contaminants that compete with phosphate source. Here, we examined whether Pt is effective in suppressing predator-type contamination. Co-culture experiment of Synechococcus with isolated P. malhamensis revealed that, although an addition of Pt at low concentrations up to 2.0 mM was not effective, increased dosage of Pt (~20 mM) resulted in the reduced grazing impact of P. malhamensis. By using unsterilized raw environmental water collected from rivers or ponds, we found that the suppression effect of Pt was dependent on the type of environmental water used. Eukaryotic microbial community analysis of the cultures using environmental water samples revealed that Paraphysomonas, a colorless Chrysophyceae, emerged and dominated under high-Pt conditions, suggesting that Paraphysomonas is insensitive to Pt compared to P. malhamensis. These findings may provide a clue for developing a strategy to reduce the impact of grazer contamination in commercial-scale microalgal cultivation.

Preparation of a magnetic metal-organic square and metal-organic cubes using 4,5-bis(2-imidazolinyl)imidazolate: slow magnetization relaxation behavior in mixed-valent octamanganese(ii/iii) clusters.

Functional metal-organic squares (MOSs) and metal-organic cubes (MOCs) are important building units for zeolite-like metal-organic frameworks (ZMOFs), which are required to exhibit solid-state properties, such as dielectric, conductive, and magnetic properties. This work describes the preparation and magnetism of a tetracopper(ii) macrocyclic complex [CuII4(im-H2bizn)4(DMSO)3(THF)](ClO4)4·8DMSO (1) (Him-H2bizn = 4,5-bis(4,5-dihydro-1H-imidazol-2-yl)imidazole) as a MOS and octametallic clusters [NiII8(im-H2bizn)12](ClO4)4·10MeOH·3H2O (2) and [MnII4MnIII4(im-H2bizn)12](ClO4)8·14MeOH (3) as MOCs. The CuII ion in 1 possesses a five-coordinated square pyramidal geometry, resulting in the formation of an M4L4-type square, which gives an estimated intramolecular antiferromagnetic interaction with an exchange coupling constant of JCu-Cu = -95 K. Meanwhile, 2 and 3 present six-coordinated octahedral geometries, giving M8L12-type cubes, of which 2 is a normal paramagnetic compound with intramolecular antiferromagnetic interactions, and where JNi-Ni = -32 K. The most notable compound 3 is a MnII4MnIII4 mixed valence state compound, which exhibits a slow magnetization relaxation behavior similar to that of single-molecule magnets. This is attributed to the contribution of magnetic anisotropy caused by the Jahn-Teller effect of the MnIII ions. Utilizing a modified Arrhenius plot to extract the values of the thermal barrier for magnetization reversal (Ea/kB) and the pre-exponential factor (τ0), the parameters for the relaxation behavior were estimated to be Ea/kB = 6.38 K and τ0 = 3.87 × 10-7 s. UV-vis spectroscopy and electrochemical measurements in solution were also carried out. Compound 3 will be expected to lead to a solid-state material in which the magnetic and dielectric properties of encapsulated small molecules cooperate with the slow magnetization relaxation properties of the MOC backbone.

MYB-like transcription factor NoPSR1 is crucial for membrane lipid remodeling under phosphate starvation in the oleaginous microalga Nannochloropsis oceanica.

Membrane lipid remodeling under phosphate (Pi) limitation, a process that replaces structural membrane phospholipids with nonphosphorus lipids, is a widely observed adaptive response in plants and algae. Here, we identified the transcription factor phosphorus starvation response 1 (NoPSR1) as an indispensable player for regulating membrane lipid conversion during Pi starvation in the microalga Nannochloropsis oceanica. Knocking out NoPSR1 scarcely perturbed membrane lipid composition under Pi-sufficient conditions but significantly impaired dynamic alteration in membrane lipids during Pi starvation. In contrast, the absence of NoPSR1 led to no obvious change in cell proliferation or storage lipid accumulation under either nutrient-sufficient or Pi-deficient conditions. Our results demonstrate a key factor controlling the membrane lipid profile during the Pi starvation response in N. oceanica.

ß-Cryptoxanthin Induces UCP-1 Expression via a RAR Pathway in Adipose Tissue.

While ß-cryptoxanthin is hypothesized to have a preventive effect on lifestyle-related diseases, its underlying mechanisms are unknown. We investigated the effect of ß-cryptoxanthin on energy metabolism in adipose tissues and its underlying mechanism. C57BL/6J mice were fed a high-fat diet (60% kcal fat) containing 0 or 0.05% ß-cryptoxanthin for 12 weeks. ß-cryptoxanthin treatment was found to reduce body fat gain and plasma glucose level, while increasing energy expenditure. The expression of uncoupling protein (UCP) 1 was elevated in adipose tissues in the treatment group. Furthermore, the in vivo assays showed that the Ucp1 mRNA expression was higher in the ß-cryptoxanthin treatment group, an effect that disappeared upon cotreatment with a retinoic acid receptor (RAR) antagonist. In conclusion, we report that ß-cryptoxanthin reduces body fat and body weight gain and that ß-cryptoxanthin increases the expression of UCP1 via the RAR pathway.

Catalytic asymmetric aza-Michael addition of fumaric monoacids with multifunctional thiourea/boronic acids.

The first chemical enantioselective synthesis of N-hydroxyaspartic acid derivatives using chiral multifunctional thiourea/boronic acid organocatalysts was developed. A series of fumaric monoacids underwent an intermolecular asymmetric aza-Michael addition of O-alkyl hydroxylamines in excellent regioselectivity. The addition of another carboxylic acid raised the enantiomeric enrichment up to 97% ee. O-Deprotection of the aza-Michael adduct provided an aspartate-derived hydroxylamine fragment applicable for KAHA (α-keto acid-hydroxylamine) ligation.

Identification of the 7S and 11S globulins as percutaneously sensitizing soybean allergens as demonstrated through epidermal application of crude soybean extract.

Cutaneous exposure to food allergens can predispose individuals to food allergies. Soybean, a major allergenic food, is an ingredient in various cosmetic products. However, the types of soybean proteins that are percutaneously sensitizing in humans or animal models remain unknown. In this study, BALB/c mice were dorsally shaved and epicutaneously exposed to a crude soybean extract including sodium dodecyl sulfate or distilled water alone. Specific IgEs secreted in response to 7S globulin (Gly m 5), 11S globulin (Gly m 6), Gly m 3, and Gly m 4 were measured using enzyme-linked immunosorbent assays or immunoblots. Exposure to soybean extract elicited the secretion of soybean-specific IgEs. Of the soybean proteins, 7S and 11S globulins acted as percutaneous sensitizers in 6/9 mice (67%). Additionally, IgE bound specifically and preferentially to the 7S globulin ß subunit. In conclusion, this is the first report to identify percutaneously sensitizing soybean allergens in a mouse model.

Worm wounding increases levels of pollen-related food allergens in soybean (Glycine max).

The levels of food allergens in worm-wounded or non-wounded green soybeans (edamame) and mature soybeans were investigated by immunoblotting and enzyme-linked immunosorbent assay (ELISA), using allergen-specific antibodies. Non-wounded and worm-wounded soybeans showed similar total protein profiles after Coomassie brilliant blue staining, but some protein bands were observed to have been changed by worm wounding. Immunoblotting with specific antibodies for major soybean allergens (Gly m 5, Gly m 6, Gly m Bd 30 K, and Kunitz soybean trypsin inhibitor) revealed that protein band profiles and intensities were not significantly changed by worm wounding. In contrast, levels of the pollen-related soybean allergens Gly m 4 and Gly m 3 were strongly increased by worm wounding in both green and mature soybeans, as detected by immunoblotting and ELISA. These results suggested that the pollen-related food allergen risk (i.e., oral allergy syndrome; OAS) from soybeans might be enhanced by worm wounding of soybeans.

Betaine Lipid Is Crucial for Adapting to Low Temperature and Phosphate Deficiency in Nannochloropsis.

Diacylglyceryl-N,N,N-trimethylhomo-Ser (DGTS) is a nonphosphorous, polar glycerolipid that is regarded as analogous to the phosphatidylcholine in bacteria, fungi, algae, and basal land plants. In some species of algae, including the stramenopile microalga Nannochloropsis oceanica, DGTS contains an abundance of eicosapentaenoic acid (EPA), which is relatively scarce in phosphatidylcholine, implying that DGTS has a unique physiological role. In this study, we addressed the role of DGTS in N. oceanica We identified two DGTS biosynthetic enzymes that have distinct domain configurations compared to previously identified DGTS synthases. Mutants lacking DGTS showed growth retardation under phosphate starvation, demonstrating a pivotal role for DGTS in the adaptation to this condition. Under normal conditions, DGTS deficiency led to an increase in the relative amount of monogalactosyldiacylglycerol, a major plastid membrane lipid with high EPA content, whereas excessive production of DGTS induced by gene overexpression led to a decrease in monogalactosyldiacylglycerol. Meanwhile, lipid analysis of partial phospholipid-deficient mutants revealed a role for phosphatidylcholine and phosphatidylethanolamine in EPA biosynthesis. These results suggest that DGTS and monogalactosyldiacylglycerol may constitute the two major pools of EPA in extraplastidic and plastidic membranes, partially competing to acquire EPA or its precursors derived from phospholipids. The mutant lacking DGTS also displayed impaired growth and a lower proportion of EPA in extraplastidic compartments at low temperatures. Our results indicate that DGTS is involved in the adaptation to low temperatures through a mechanism that is distinct from the DGTS-dependent adaptation to phosphate starvation in N. oceanica.