1-Deoxynojirimycin containing Morus alba leaf-based food modulates the gut microbiome and expression of genes related to obesity.

BACKGROUND: Obesity is a serious disease with an alarmingly high incidence that can lead to other complications in both humans and dogs. Similar to humans, obesity can cause metabolic diseases such as diabetes in dogs. Natural products may be the preferred intervention for metabolic diseases such as obesity. The compound 1-deoxynojirimycin, present in Morus leaves and other sources has antiobesity effects. The possible antiobesity effect of 1-deoxynojirimycin containing Morus alba leaf-based food was studied in healthy companion dogs (n = 46) visiting the veterinary clinic without a history of diseases. Body weight, body condition score (BCS), blood-related parameters, and other vital parameters of the dogs were studied. Whole-transcriptome of blood and gut microbiome analysis was also carried out to investigate the possible mechanisms of action and role of changes in the gut microbiome due to treatment. RESULTS: After 90 days of treatment, a significant antiobesity effect of the treatment food was observed through the reduction of weight, BCS, and blood-related parameters. A whole-transcriptome study revealed differentially expressed target genes important in obesity and diabetes-related pathways such as MLXIPL, CREB3L1, EGR1, ACTA2, SERPINE1, NOTCH3, and CXCL8. Gut microbiome analysis also revealed a significant difference in alpha and beta-diversity parameters in the treatment group. Similarly, the microbiota known for their health-promoting effects such as Lactobacillus ruminis, and Weissella hellenica were abundant (increased) in the treatment group. The predicted functional pathways related to obesity were also differentially abundant between groups. CONCLUSIONS: 1-Deoxynojirimycin-containing treatment food have been shown to significantly improve obesity. The identified genes, pathways, and gut microbiome-related results may be pursued in further studies to develop 1-deoxynojirimycin-based products as candidates against obesity.

Assessing the Brain Death/Death by Neurologic Criteria Determination Process in Korea: Insights from 10-Year Noncompleted Donation Data.

BACKGROUND: This study aimed to analyze the current status of brain death/death by neurologic criteria (BD/DNC) determination in Korea over a decade, identifying key areas for improvement in the process. METHODS: We conducted a retrospective analysis of data from the Korea Organ Donation Agency spanning 2011 to 2021, focusing on donors whose donations were not completed. The study reviewed demographics, medical settings, diagnoses, and outcomes, with particular emphasis on cases classified as nonbrain death and those resulting in death by cardiac arrest during the BD/DNC assessment. RESULTS: Of the 5047 patients evaluated for potential brain death from 2011 to 2021, 361 were identified as noncompleted donors. The primary reasons for noncompletion included nonbrain death (n = 68, 18.8%), cardiac arrests during the BD/DNC assessment process (n = 80, 22.2%), organ ineligibility (n = 151, 41.8%), and logistical and legal challenges (n = 62, 17.2%). Notably, 25 (36.8%) of them failed to meet the minimum clinical criteria, and 7 of them were potential cases of disagreement between the two clinical examinations. Additionally, most cardiac arrests (n = 44, 55.0%) occurred between the first and second examinations, indicating management challenges in critically ill patients during the assessment period. CONCLUSIONS: Our study highlights significant challenges in the BD/DNC determination process, including the need for improved consistency in neurologic examinations and the management of critically ill patients. The study underscores the importance of refining protocols and training to enhance the accuracy and reliability of brain death assessments, while also ensuring streamlined and effective organ donation practices.

Mulberry Leaf Supplements Effecting Anti-Inflammatory Genes and Improving Obesity in Elderly Overweight Dogs.

Overweight and obesity, associated with various health complications, refer to abnormal or excessive fat accumulation conditions that harm health. Like humans, obesity is a growing problem in dogs, which may increase the risk of serious diseases such as diabetes and cancer. Mulberry leaf has shown potential anti-obesity and anti-diabetes effects in several studies. Our research studied the impact of mulberry leaf supplements in healthy old overweight dogs for 12 weeks. Blood and fecal samples were collected from the dogs before and after treatment for different analyses, including whole transcriptome and gut microbiome analysis. The Body Condition Score (BCS) and blood glucose levels were significantly decreased in all mulberry treatment groups, which justifies the anti-obesity effect of mulberry leaf in dogs. Throughout the whole transcriptome study, the downregulation of PTX3 and upregulation of PDCD-1, TNFRSF1B, RUNX3, and TICAM1 genes in the high mulberry group were found, which have been associated with anti-inflammatory effects in the literature. It may be an essential gene expression mechanism responsible for the anti-inflammatory and, subsequently, anti-obesity effects associated with mulberry leaf treatment, as confirmed by real-time polymerase chain reaction analysis. In microbiome analysis, Papillibacter cinnamivorans, related to the Mediterranean diet, which may cause anti-inflammatory effects, were abundant in the same treatment group. Further studies may be required to establish the gene expression mechanism and role of abundant bacteria in the anti-obesity effect of mulberry supplements in dogs. Overall, we propose mulberry leaves as a portion of food supplements for improving blood glucose levels and the anti-inflammation of blood in companion dogs.

Rufomycins or Ilamycins: Naming Clarifications and Definitive Structural Assignments.

Rufomycin and ilamycin are synonymous for the same class of cyclopeptides, currently encompassing 33 structurally characterized isolates and 9 semisynthetic derivatives. Elucidation of new structures prioritized the consolidation of the names and established the structures of four diastereoisomeric rufomycins with a 2-piperidinone, named rufomycins 4-7, including full 1H/13C NMR assignments. The characteristic HSQC cross-peak for the CH-5, the hemiaminal carbon in amino acid #5, allows assignment of the stereocenters C-4 and C-5 within this ring. Semisynthetic derivatives (rufomycinSS 1, 2, and 3) were prepared from a rufomycins 4 and 6 mixture to validate the structural assignments. Based on the X-ray crystal structures of rufomycins 2 and 4, considering the NMR differences of rufomycins 7 vs 4-6 compared to rufomycinSS 1 vs 2 and 3, and taking into account that two major conformers, A and B, occur in both rufomycinSS 2 and 3, structural modeling was pursued. Collectively, this paper discusses the NMR spectroscopic differences of the stereoisomers and their possible 3D conformers and correlates these with the anti-Mycobacterium tuberculosis activity. In addition, a look at the history prioritizes names and numbering schemes for this group of antibiotics and leads to consolidated nomenclature for all currently known members, natural and semisynthetic derivatives, and serves to accommodate future discoveries.

Impact of an anti-Salmonella. Typhimurium Bacteriophage on intestinal microbiota and immunity status of laying hens.

Typhoid is a distinct gastrointestinal disease that largely affects the public by consumption of inadequately or partially cooked eggs from contaminated laying hen farms. This has led the research on laying hens to focus on controlling the contamination by an effective anti-Salmonella spp. agent in the intestine. The treatments included, control, without challenge; PC, Salmonella typhimurium challenged (STC); BP5, 5 ppm bacteriophage/kg + STC; BP10, 10 ppm bacteriophage/kg + STC, on Salmonella shedding, body organs inflammatory reactions, and expression of toll-like receptor (TLR), pro-inflammatory cytokines, and heat shock protein (HSP) in the jejunum, liver,and thigh muscle in the STC laying hens. The RT-PCR method was used to enumerate the number of Salmonella typhimurium in the organs. The birds in the STC groups exhibited the increased population of Salmonella spp. in the excreta (p < .01). In the STC groups, the BP5 and BP10 laying hens exhibited a lower (p < .01) population of Salmonella spp. in the excreta at d 7 after STC. Supplementation of bacteriophage significantly decreased (p < .01) the colonization of S. Typhimurium in the spleen, oviduct, caecum and excreta. Among the STC treatments, the BP10 laying hens showed lower (p < .01) mRNA expression of interferon-γ (IFNγ) and TLR-4 in the jejunum compared with the PC treatment. After the STC, dietary supplementation with BP5 or BP10 decreased (p < .01) the mRNA expressions of IFNγ, HSP-27 and tumour necrosis factor-α in the liver compared with the PC treatment. These results suggest that bacteriophage can be used as an effective agent to decrease S. Typhimurium contamination in laying hens and possibly lower S. Typhimurium transfer to foods.

Preparation and availability analysis of glycoprotein from canola meal.

The purpose of this study is to examine the possibility of use in various fields such as cosmetics and food industry by extracting, separating, and purifying canola glycoprotein(hreinafter referred to as CNG) and comparing general characteristics and physiological activities with commercially available carrot glycoprotein(hreinafter referred to as CRG). The CNG had a protein content of 13.12%, which is higher than that of common vegetable glycoproteins, and much higher than the CRG of 2.36%. The molecular weight distribution of the CNG was 263-310 Da, which showed a lower molecular weight distribution than the 566-628 Da of the CRG. The total polyphenol content of the CNG was 29.89 mg/g, which was higher than that of the CRG measured at 1.76 mg g-1. The DPPP radical scavenging activity of CNG and carrot glycoprotein were 10.07 mg mL-1 and 7.76 mg mL-1, respectively, indicating that CNG had slightly higher electron donating ability than CRG. Total antioxidant activity of CNG was 26.84 mg AA eq/g and CRG was 10.53 mg AA eq/g.

Relationships Between Perspective-Taking, Empathic Concern, and Self-rating of Empathy as a Physician Among Medical Students.

OBJECTIVE: The aim of this study was to ascertain the relationships between perspective-taking, empathic concern, and self-rating of empathy as a physician among medical students. METHODS: This study analyzed the questionnaire responses of 152 medical students enrolled in Ajou University School of Medicine, Suwon, Republic of Korea, in 2018. As measurement instruments, the authors applied the Interpersonal Reactivity Index (IRI) and Korean Student Version of the Jefferson Scale of Physician Empathy (Korean JSPE-S), and then examined participant characteristic variables based on the obtained data and conducted subsequent correlation analyses of subscales, one-way ANOVA, and regression analyses. RESULTS: Medical students with clinical clerkship experience demonstrated higher levels of perspective-taking and empathy as physicians than did students without experience. Moreover, perspective-taking and empathic concern were significant predictors of medical students' empathy as physicians in the regression model. CONCLUSIONS: Medical students with higher scores in perspective-taking and empathic concern demonstrated higher levels of perception regarding the necessity and importance of empathy as a physician in patient-physician relationships. Therefore, in actual medical situations with patient-centered therapy, to enhance the levels of physician empathy, medical education should focus on the understanding of other persons' opinions and interpersonal interactions accompanied by empathic concern.

Fruit and vegetable consumption and the metabolic syndrome: a systematic review and dose-response meta-analysis.

A systematic review and meta-analysis of observational studies were performed to assess the dose-response associations between fruit or vegetable consumption and the chance of the metabolic syndrome (MetS). Studies on the association between fruit or vegetable consumption and the risk of the MetS published from January 1958 to 30 October 2018 were searched using the PubMed, MEDLINE and Embase databases, and the references of relevant articles were reviewed. Random-effects models were used to estimate the summary OR with 95 % CI for the MetS, and dose-response analysis was conducted to quantify the associations. Heterogeneity among studies was evaluated using Q and I2 statistics. A total of nine observational studies (seven cross-sectional studies and two cohort studies) were included in the meta-analysis. In a dose-response analysis of cohort studies and cross-sectional studies, the summary estimate of the MetS for an increase of 100 g/d in fruit consumption (nine studies) was 0·97 (95 % CI 0·95, 0·99; I2 = 26·7 %), whereas an increase of 100 g/d in vegetable consumption (nine studies) was not associated with a reduction in the MetS (OR 0·98; 95 % CI 0·96, 1·01; I2 = 54·6 %). In conclusion, an increased intake of fruit may reduce the risk of the MetS. For future research, prospective studies or randomised clinical trials are needed to identify the effects of fruits and vegetables by variety on the risk of the MetS.

Dairy food consumption is associated with a lower risk of the metabolic syndrome and its components: a systematic review and meta-analysis.

A systematic review and a meta-analysis of observational studies were performed to assess the dose-response relationship between specific types of dairy foods and the risk of the metabolic syndrome (MetS) and its components. Studies of dairy foods and the risk of the MetS and its components published up to June 2016 were searched using PubMed, EMBASE and a reference search. Random-effects models were used to estimate the pooled relative risks (RR) with 95 % CI. Finally, ten cross-sectional studies, two nested case-control studies and twenty-nine cohort studies were included for the analysis. In a dose-response analysis of cohort studies and cross-sectional studies, the pooled RR of the MetS for a one-serving/d increment of total dairy food (nine studies) and milk (six studies) consumption (200 g/d) were 0·91 (95 % CI 0·85, 0·96) and 0·87 (95 % CI 0·79, 0·95), respectively. The pooled RR of the MetS for yogurt (three studies) consumption (100 g/d) was 0·82 (95 % CI 0·73, 0·91). Total dairy food consumption was associated with lower risk of MetS components, such as hyperglycaemia, elevated blood pressure, hypertriacylglycerolaemia and low HDL- cholesterol. A one-serving/d increment of milk was related to a 12 % lower risk of abdominal obesity, and a one-serving/d increment of yogurt was associated with a 16 % lower risk of hyperglycaemia. These associations were not significantly different by study design, study location or adjustment factors. This meta-analysis showed that specific types of dairy food consumption such as milk and yogurt as well as total dairy food consumption were inversely related to risk of the MetS and its components.

Microquantitation of Prostate-Speciflc Antigen by Using Antibody-Conjugated Magnetic Microsphere Beads.

Prostate-specific antigen (PSA) is a glycoprotein that is secreted by prostate gland epithelial cells, and elevation of PSA level in serum is often observed with prostate cancer or prostate disorders. Therefore, detection of PSA level in patient specimens is used as a diagnostic marker when screening of prostate cancer. In this study, we developed PSA antibody-conjugated microsphere beads that can be used for quantitation of PSA. We optimized the procedure for bead preparation and validated the detection analysis by using LNCaP and DU-145 prostate cancer cell lysates. By applying the procedure, extracellular PSA from culture media of LNCaP cells and standard PSA proteins were quantified to assess whether the antibody-conjugated microsphere bead can be used to detect trace amounts of PSA. The PSA level results obtained by using the antibody-conjugated microsphere beads indicate that the procedure is sensitive and quantitative in analyzing PSA. Taken together, the results suggest that the method is suitable for microquantitation of PSA from patient specimens.

Efficacy of UV-TiO2 photocatalysis technology for inactivation of Escherichia coli K12 on the surface of blueberries and a model agar matrix and the influence of surface characteristics.

Surface disinfection of fresh blueberries is an important food safety challenge due to the delicate texture and short shelf life of these small fruits. A newly designed water-assisted photocatalytic reactor was developed for disinfection of fruits with a delicate texture and complex surface characteristics. Efficacy of UV-TiO2 photocatalysis was evaluated in comparison with UV alone for inactivation of Escherichia coli K12 (as a surrogate for Escherichia coli O157:H7) inoculated onto the surface of the blueberry skin, calyx, and an experimentally prepared agar matrix that was used as a model matrix. Influence of surface characteristics such as surface hydrophobicity and surface free energy on bacterial adhesion were also investigated. The initial bacterial population on all surfaces was approximately 7.0 log CFU/g. UV-TiO2 photocatalysis (4.5 mW/cm2) for 30 s achieved comparatively higher bacterial reductions of 5.3 log and 4.6 log CFU/g on blueberry skin and agar matrix surfaces, respectively, than 4.5 log and 3.4 log CFU/g reductions for UV alone (6.0 mW/cm2). Total phenolic and total anthocyanin contents of fruits were significantly increased after both UV-TiO2 and UV treatments, compared with water washed control fruits. UV-TiO2 photocatalysis technology is a non-chemical and residue-free method with reduced water usage for surface disinfection of fresh blueberries.

Disruption of a regulatory loop between DUSP1 and p53 contributes to hepatocellular carcinoma development and progression.

BACKGROUND & AIMS: Altered expression of dual specificity phosphatase 1 (DUSP1) is common in tumors including hepatocellular carcinoma (HCC), and is predictive of tumor progression and poor prognosis. However, the tumor suppressive role of DUSP1 has yet to be clearly elucidated. METHODS: The molecular mechanisms of tumor suppression that were investigated were induction of apoptosis, cell cycle inhibition, and regulation of p53. Additionally, the antitumor effect of DUSP1 was assessed using a mouse model. Associated signaling pathways in HCC cells and tissues were examined. RESULTS: Downregulation of DUSP1 expression was significantly correlated with poor differentiation (p<0.001) and advanced HCC stage (p=0.023). DUSP1 expression resulted in HCC suppression and longer survival (p=0.0002) in a xenoplant mice model. DUSP1 inhibited p38 MAPK phosphorylation and subsequently suppressed HSP27 activation, resulting in enhanced p53 phosphorylation at sites S15, S20, and S46 in HCC cells. Enhanced p53 activation induced the expression of target genes p21 and p27, which are linked to cell cycle arrest and apoptosis. Thus, DUSP1 was potentially linked to p53 activation via the p38 MAPK/HSP27 pathway. Wild-type but not mutant p53 transcriptionally upregulated DUSP1 via its DNA-binding domain. DUSP1 and p53 might collaborate to suppress tumors in hepatocarcinogenesis via a positive regulatory loop. CONCLUSIONS: Our results revealed that disruption of a positive regulatory loop between DUSP1 and p53 promoted HCC development and progression, providing a rationale for a therapeutic agent that restores DUSP1 in HCC.

Lipocalin-2 negatively modulates the epithelial-to-mesenchymal transition in hepatocellular carcinoma through the epidermal growth factor (TGF-beta1)/Lcn2/Twist1 pathway.

UNLABELLED: Lipocalin-2 (Lcn2) is preferentially expressed in hepatocellular carcinoma (HCC). However, the functional role of Lcn2 in HCC progression is still poorly understood, particularly with respect to its involvement in invasion and metastasis. The purpose of this study was to investigate whether Lcn2 is associated with the epithelial-mesenchymal transition (EMT) in HCC and to elucidate the underlying signaling pathway(s). Lcn2 was preferentially expressed in well-differentiated HCC versus liver cirrhosis tissues, and its expression was positively correlated with the stage of HCC. The characteristics of EMT were reversed by adenoviral transduction of Lcn2 into SH-J1 cells, including the down-regulation of N-cadherin, vimentin, alpha-smooth muscle actin, and fibronectin, and the concomitant up-regulation of CK8, CK18, and desmoplakin I/II. Knockdown of Lcn2 by short hairpin RNA (shRNA) in HKK-2 cells expressing high levels of Lcn2 was associated with EMT. Epidermal growth factor (EGF) or transforming growth factor beta1 (TGF-ß1) treatment resulted in down-regulation of Lcn2, accompanied by an increase in Twist1 expression and EMT in HCC cells. Stable Lcn2 expression in SH-J1 cells reduced Twist1 expression, inhibited cell proliferation and invasion in vitro, and suppressed tumor growth and metastasis in a mouse model. Furthermore, EGF or TGF-ß1 treatment barely changed EMT marker expression in SH-J1 cells ectopically expressing Lcn2. Ectopic expression of Twist1 induced EMT marker expression even in cells expressing Lcn2, indicating that Lcn2 functions downstream of growth factors and upstream of Twist1. CONCLUSION: Together, our findings indicate that Lcn2 can negatively modulate the EMT in HCC cells through an EGF (or TGF-ß1)/Lcn2/Twist1 pathway. Thus, Lcn2 may be a candidate metastasis suppressor and a potential therapeutic target in HCC.

Activation of mammalian target of rapamycin complex 1 (mTORC1) and Raf/Pyk2 by growth factor-mediated Eph receptor 2 (EphA2) is required for cholangiocarcinoma growth and metastasis.

Eph receptor 2 (EphA2) overexpression is frequently accompanied by the loss of its cognate ligand during tumor progression. However, the molecular mechanism of this ligand-independent promotion of tumor by EphA2 remains unclear in highly malignant and fatal cholangiocarcinoma (CC). We examined the biological role of EphA2 in tumor growth and metastasis in CC tissues and cells according to the degree of differentiation and we explored the downstream signaling pathways of EphA2. Growth factor-mediated EphA2 overexpression itself leads to the activation of the mammalian target of rapamycin complex 1 (mTORC1) and extracellular signal-regulated kinase (ERK) pathways through ligand-independent activation of EphA2 (phosphorylation of S897). An in vitro soft agar assay and in vivo orthotopic or subcutaneous tumor model showed that EphA2 enhanced colony formation and accelerated tumor growth, and which seemed to be mainly associated with Akt (T308)/mTORC1 activation. Aberrant expression and activation of EphA2 was also associated with poorer differentiation and higher metastatic ability. Enhanced metastatic ability was also observed in an orthotopic tumor model or lung metastasis model, correlating with Pyk2(Y402)/c-Src/ERK activation in addition to activation of the canonical Raf/MEK/ERK pathway. The mTORC1 and Raf/Pyk2 pathways also appeared to affect each other. These results suggest that growth factor-mediated EphA2 might be involved in tumor growth and metastasis through activation of the mTORC1 and Raf/Pyk2 pathways. Therapeutic strategies that target EphA2 and its downstream effectors may be useful to control CC. (HEPATOLOGY 2013;57:2248-2260).

4-Substituted quinazoline derivatives as novel EphA2 receptor tyrosine kinase inhibitors.

Erythropoietin-producing hepatocellular receptor tyrosine kinase subtype A2 (EphA2) is an attractive therapeutic target for suppressing tumor progression. In our efforts to discover novel small molecules to inhibit EphA2, a class of compound based on 4-substituted quinazoline containing 7-(morpholin-2-ylmethoxy) group was identified as a novel hit by high throughput screening campaign. Structural modification of parent quinazoline scaffolds by introducing substituents on aniline displayed potent inhibitory activities toward EphA2.

Identification of a vitamin D3-specific hydroxylase genes through actinomycetes genome mining.

We previously completed whole-genome sequencing of a rare actinomycete named Sebekia benihana, and identified the complete S. benihana cytochrome P450 complement (CYPome), including 21 cytochrome P450 hydroxylase (CYP), seven ferredoxin (FD), and four ferredoxin reductase (FDR) genes. Through targeted CYPome disruption, a total of 32 S. benihana CYPome mutants were obtained. Subsequently, a novel cyclosporine A region-specific hydroxylase was successfully determined to be encoded by a CYP-sb21 gene by screening the S. benihana CYPome mutants. Here, we report that S. benihana is also able to mediate vitamin D3 (VD3) hydroxylation. Among the 32 S. benihana CYPome mutants tested, only a single S. benihana CYP mutant, ΔCYP-sb3a, failed to show regio-specific hydroxylation of VD3 to 25-hydroxyvitamin D3 and 1α,25-dihydroxyvitamin D3. Moreover, the VD3 hydroxylation activity in the ΔCYP-sb3a mutant was restored by CYP-sb3a gene complementation. Since all S. benihana FD and FDR disruption mutants maintained VD3 hydroxylation activity, we conclude that CYP-sb3a, a member of the bacterial CYP107 family, is the only essential component of the in vivo regio-specific VD3 hydroxylation process in S. benihana. Expression of the CYP-sb3a gene exhibited VD3 hydroxylation in the VD3 non-hydroxylating Streptomyces coelicolor, implying that the regio-specific hydroxylation of VD3 is carried out by a specific P450 hydroxylase in S. benihana.

A novel regio­specific cyclosporin hydroxylase gene revealed through the genome mining of Pseudonocardia autotrophica.

The regio-specific hydroxylation at the 4th N-methyl leucine of the immunosuppressive agent cyclosporin A (CsA) was previously proposed to be mediated by a unique cytochrome P450 hydroxylase (CYP), CYP-sb21 from the rare actinomycetes Sebekia benihana. Interestingly, a different rare actinomycetes species, Pseudonocardia autotrophica, was found to possess a different regio-selectivity, the preferential hydroxylation at the 9th N-methyl leucine of CsA. Through an in silico analysis of the whole genome of P. autotrophica, we describe here the classification of 31 total CYPs in P. autotrophica. Three putative CsA CYP genes, showing the highest sequence homologies with CYPsb21, were successfully inactivated using PCR-targeted gene disruption. Only one knock-out mutant, ΔCYP-pa1, failed to convert CsA to its hydroxylated forms. The hydroxylation activity of CsA by CYP-pa1 was confirmed by CYP-pa1 gene complementation as well as heterologous expression in the CsA non-hydroxylating Streptomyces coelicolor. Moreover, the cyclosporine regio-selectivity of CYP-pa1 expressed in the ΔCYP-sb21 S. benihana mutant strain was also confirmed unchanged through cross complementation. These results show that preferential regio-specific hydroxylation at the 9th N-methyl leucine of CsA is carried out by a specific P450 hydroxylase gene in P. autotrophica, CYP-pa1, setting the stage for the biotechnological application of CsA regioselective hydroxylation.

A review of brain-computer interface games and an opinion survey from researchers, developers and users.

In recent years, research on Brain-Computer Interface (BCI) technology for healthy users has attracted considerable interest, and BCI games are especially popular. This study reviews the current status of, and describes future directions, in the field of BCI games. To this end, we conducted a literature search and found that BCI control paradigms using electroencephalographic signals (motor imagery, P300, steady state visual evoked potential and passive approach reading mental state) have been the primary focus of research. We also conducted a survey of nearly three hundred participants that included researchers, game developers and users around the world. From this survey, we found that all three groups (researchers, developers and users) agreed on the significant influence and applicability of BCI and BCI games, and they all selected prostheses, rehabilitation and games as the most promising BCI applications. User and developer groups tended to give low priority to passive BCI and the whole head sensor array. Developers gave higher priorities to "the easiness of playing" and the "development platform" as important elements for BCI games and the market. Based on our assessment, we discuss the critical point at which BCI games will be able to progress from their current stage to widespread marketing to consumers. In conclusion, we propose three critical elements important for expansion of the BCI game market: standards, gameplay and appropriate integration.

Prebiotic Vitamin B3 Synthesis in Carbonaceous Planetesimals.

Aqueous chemistry within carbonaceous planetesimals is promising for synthesizing prebiotic organic matter essential to all life. Meteorites derived from these planetesimals delivered these life building blocks to the early Earth, potentially facilitating the origins of life. Here, we studied the formation of vitamin B3 as it is an important precursor of the coenzyme NAD(P)(H), which is essential for the metabolism of all life as we know it. We propose a new reaction mechanism based on known experiments in the literature that explains the synthesis of vitamin B3. It combines the sugar precursors glyceraldehyde or dihydroxyacetone with the amino acids aspartic acid or asparagine in aqueous solution without oxygen or other oxidizing agents. We performed thermochemical equilibrium calculations to test the thermodynamic favorability. The predicted vitamin B3 abundances resulting from this new pathway were compared with measured values in asteroids and meteorites. We conclude that competition for reactants and decomposition by hydrolysis are necessary to explain the prebiotic content of meteorites. In sum, our model fits well into the complex network of chemical pathways active in this environment.

Methionine Supplementation Alleviates the Germ Cell Apoptosis Increased by Maternal Caffeine Intake in a C. elegans Model.

Caffeine (1,3,7-trimethylxanthine) is a widely consumed bioactive substance worldwide. Our recent study showed that a reduction in both reproduction and yolk protein production (vitellogenesis) caused by caffeine intake were improved by vitamin B12 supplementation, which is an essential co-factor in methionine metabolism. In the current study, we investigated the role of methionine in the reproduction of caffeine-ingested animals (CIAs). We assessed the effect of methionine metabolism on CIAs and found that caffeine intake decreased both methionine levels and essential enzymes related to the methionine cycle. Furthermore, we found that the caffeine-induced impairment of methionine metabolism decreased vitellogenesis and increased germ cell apoptosis in an LIN-35/RB-dependent manner. Interestingly, the increased germ cell apoptosis was restored to normal levels by methionine supplementation in CIAs. These results indicate that methionine supplementation plays a beneficial role in germ cell health and offspring development by regulating vitellogenesis.