C-Peptide Level in Fasting Plasma and Pooled Urine Predicts HbA1c after Hospitalization in Patients with Type 2 Diabetes Mellitus

In this study, we investigate how measures of insulin secretion and other clinical information affect long-term glycemic control in patients with type 2 diabetes mellitus. Between October 2012 and June 2014, we monitored 202 diabetes patients who were admitted to the hospital of Asahi Life Foundation for glycemic control, as well as for training and education in diabetes management. We measured glycated hemoglobin (HbA1c) six months after discharge to assess disease management. In univariate analysis, fasting plasma C-peptide immunoreactivity (F-CPR) and pooled urine CPR (U-CPR) were significantly associated with HbA1c, in contrast to ΔCPR and C-peptide index (CPI). This association was strongly independent of most other patient variables. In exploratory factor analysis, five underlying factors, namely insulin resistance, aging, sex differences, insulin secretion, and glycemic control, represented patient characteristics. In particular, insulin secretion and resistance strongly influenced F-CPR, while insulin secretion affected U-CPR. In conclusion, the data indicate that among patients with type 2 diabetes mellitus, F-CPR and U-CPR may predict improved glycemic control six months after hospitalization.     

A Comparative Analysis of the Molecular Features of MANF and CDNF

Cerebral dopamine neurotrophic factor (CDNF) is a paralogous protein of mesencephalic astrocyte-derived neurotrophic factor (MANF). Both proteins have been reported to show a common cytoprotective effect on dopaminergic neurons as a secretory protein containing the KDEL-like motif of the ER retrieval signal at the C-terminus, RTDL in MANF and [Q/K]TEL in CDNF among many species, although functions of paralogous proteins tend to differ from each other. In this study, we focused on post-translational regulations of their retention in the endoplasmic reticulum (ER) and secretion and performed comparative experiments on characterization of mouse MANF and mouse CDNF according to our previous report about biosynthesis and secretion of mouse MANF using a NanoLuc system. In this study, co-expression of glucose-regulated protein 78 kDa (GRP78), KDEL receptor 1 or mutant Sar1 into HEK293 cells similarly decreased MANF and CDNF secretion with some degree of variation. Next, we investigated whether CDNF affects the secretion of mouse cysteine-rich with EGF-like domains 2 (CRELD2) because mouse wild-type (wt) MANF but not its KDEL-like motif deleted mutant (ΔC_MANF) was found to promote the CRELD2 release from the transfected cells. Co-expressing CRELD2 with wt or ΔC CDNF, we found that CDNF and ΔC_MANF hardly elevated the CRELD2 secretion. We then investigated effects of the four or six C-terminal amino acids of MANF and CDNF on the CRELD2 secretion. As a result, co-transfection of mouse CDNF having the mouse MANF-type C-terminal amino acids (CDNF_RTDL and CDNF_SARTDL) increased the CRELD2 secretion to a small extent, but mouse CDNF having human CDNF-type ones (CDNF_KTEL and CDNF_HPKTEL) well increased the CRELD2 secretion. On the other hand, the replacement of C-terminal motifs of mouse MANF with those of mouse CDNF (MANF_QTEL and MANF_YPQTEL) enhanced the CRELD2 secretion, and the mouse MANF having human CDNF-type ones (MANF_KTEL and MANF_HPKTEL) dramatically potentiated the CRELD2 secretion. These results indicate that the secretion of mouse MANF and mouse CDNF is fundamentally regulated in the same manner and that the variation of four C-terminal amino acids in the MANF and CDNF among species might influence their intracellular functions. This finding could be a hint to identify physiological functions of MANF and CDNF.     

Differentiation of rat adipose tissue-derived stem cells into neuron-like cells by valproic acid,a histone deacetylase inhibitor

Valproic acid (VPA) is a widely used antiepileptic drug, which has recently been reported to modulate the neuronal differentiation of adipose tissue-derived stem cells (ASCs) in humans and dogs. However, controversy exists as to whether VPA really acts as an inducer of neuronal differentiation of ASCs. The present study aimed to elucidate the effect of VPA in neuronal differentiation of rat ASCs. One or three days of pretreatment with VPA (2 mM) followed by neuronal induction enhanced the ratio of immature neuron marker βIII-tubulin-positive cells in a time-dependent manner, where the majority of cells also had a positive signal for neurofilament medium polypeptide (NEFM), a mature neuron marker. RT-PCR analysis revealed increases in the mRNA expression of microtubule-associated protein 2 (MAP2) and NEFM mature neuron markers, even without neuronal induction. Three-days pretreatment of VPA increased acetylation of histone H3 of ASCs as revealed by immunofluorescence staining. Chromatin immunoprecipitation assay also showed that the status of histone acetylation at H3K9 correlated with the gene expression of TUBB3 in ASCs by VPA. These results indicate that VPA significantly promotes the differentiation of rat ASCs into neuron-like cells through acetylation of histone H3, which suggests that VPA may serve as a useful tool for producing transplantable cells for future applications in clinical treatments.     

Precipitation of sword bean proteins by heating and addition of magnesium chloride in a crude extract

Sword bean (Canavalia gladiata) seeds are a traditional food in Asian countries. In this study, we aimed to determine the optimal methods for the precipitation of sword bean proteins useful for the food development. The soaking time for sword beans was determined by comparing it with that for soybeans. Sword bean proteins were extracted from dried seeds in distilled water using novel methods. We found that most proteins could be precipitated by heating the extract at more than 90 °C. Interestingly, adding magnesium chloride to the extract at lower temperatures induced specific precipitation of a single protein with a molecular weight of approximately 48 kDa. The molecular weight and N-terminal sequence of the precipitated protein was identical to that of canavalin. These data suggested that canavalin was precipitated by the addition of magnesium chloride to the extract. Our results provide important insights into the production of processed foods from sword bean.     

Female preference for large waving claws in the dotillid crab <Emphasis Type="Italic">Ilyoplax pusilla</Emphasis>

Male Ilyoplax pusilla perform a waving display, a simple up-down movement of the claws during the reproductive season. Large males dedicated most of their surface activity to waving displays and gained higher mating success. On the other hand, small males infrequently performed waving displays and devoted their time exclusively to foraging. To examine female preference for the size of waving males, two female-release experiments were conducted. In the experiments, we recorded female choice between small- and large-waving claw models over short (10 cm) and long (25 cm) distances. In both the short- and long-distance choice experiments, significantly more females chose the large-claw model over the small-claw model. The following characteristics may produce obvious age-dependent sexual advertisement in I. pusilla, which grows throughout a life: (1) the strong female preference for large claws; (2) the short, 2-year lifespan that includes only two reproductive seasons; and (3) the lack of alternative mating strategies (e.g., surface mating).     

Social jetlag affects subjective daytime sleepiness in school-aged children and adolescents: A study using the Japanese version of the Pediatric Daytime Sleepiness Scale (PDSS-J)

The aim of this study was to elucidate the level of daytime sleepiness in Japanese school-aged children and adolescents, and to examine associated factors including sleep loss and social jetlag using the Japanese version of the Pediatric Daytime Sleepiness Scale (PDSS-J). After the linguistic validation of the PDSS-J with a multi-step translation methodology, consisting of forward translation, back translation, expert review and cognitive debriefing interviews, we conducted a psychometric validation for 492 students aged 11–16 years (46.7% boys) of public elementary school, junior high school and high school, using the PDSS-J, the Karolinska Sleepiness Scale (KSS), and bedtimes and wake-up times on school days and free days. Internal consistency (Cronbach’s alpha) of the PDSS-J was 0.77, and the test–retest reliability demonstrated by the intraclass coefficient was 0.88. Multivariate logistic regression analysis revealed that both short sleep duration and social jetlag were identified as factors associated with daytime sleepiness, after adjustment for age and sex. PDSS-J scores were significantly higher in the group with large social jetlag with or without sufficient sleep duration than in the group with sufficient sleep duration and small social jetlag. The PDSS-J is an important tool for assessing daytime sleepiness, given its ease of administration and robust psychometric properties. The impact of not only sleep loss but also social jetlag on daytime sleepiness among school-aged children and adolescents must be fully taken into account.     

Deer herbivory affects the functional diversity of forest floor plants via changes in competition-mediated assembly rules

Distorted plant diversity patterns due to ungulate herbivory could be explained by changes in community assembly processes, but the effects of ungulate herbivory on plant community assembly remain unclear. Here, we examined the role of deer herbivory in the regulation of the assembly processes of a forest floor plant community by assessing species and functional diversity in over- and no-grazing plots (control and exclosure plots, respectively) in Shiretoko National Park in Japan. Compared with the exclosure plot, vegetation coverage was considerably lower, and species richness and diversity were higher in the control plot. Functional traits associated with competitive ability (leaf area and chlorophyll content) were significantly higher in the exclosure plot. The pattern of functional diversity changed from overdispersion to clustering with an increase in local crowdedness. This trait clustering indicates that the local communities that were free from ungulate disturbance gradually became dominated by some competitively superior plant species, which led to low species diversity and biotic homogenization. In contrast, the reduction in vegetation due to overgrazing by deer resulted in an increase in the relative importance of stochastic assembly processes, which enabled the coexistence of various species, including less competitive ones. Our results emphasize that although deer overabundance is of concern, their complete exclusion has a negative consequence from an ecological perspective. Because deer herbivory is an inherent process that affects the biodiversity of plants on the forest floor, the establishment of fences requires careful consideration to ensure the conservation of ecological processes and their associated biodiversity.