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Epidemiological evidence in humans has suggested that maternal infections and maternal autoimmune diseases are involved in the pathogenesis of autism spectrum disorder. Animal studies supporting human results have shown that maternal immune activation causes brain and behavioral alterations in offspring. Several underlying mechanisms, including interleukin-17A imbalance, have been identified. Apart from the pro-inflammatory effects of interleukin-17A, there is also evidence to support the idea that it activates neuronal function and defines cognitive behavior. In this review, we examined the signaling pathways in both immunological and neurological contexts that may contribute to the improvement of autism spectrum disorder symptoms associated with maternal blocking of interleukin-17A and adult exposure to interleukin-17A. We first describe the epidemiology of maternal immune activation then focus on molecular signaling of the interleukin-17 family regarding its physiological and pathological roles in the embryonic and adult brain. In the future, it may be possible to use interleukin-17 antibodies to prevent autism spectrum disorder., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fujitani, Miyajima, Otani and Liu.)

Our previous studies suggested that Alaska pollack protein (APP) intake increases skeletal muscle mass and that it may cause a slow-to-fast shift in muscle fiber type in rats fed a high-fat diet after 56 days of feeding. In this study, we explored whether dietary APP induces acute and sustainable skeletal muscle hypertrophy in rats fed a normal-fat diet. Male 5-week-old Sprague-Dawley rats were divided into four groups and fed a purified ingredient-based high-fat diet or a purified ingredient-based normal-fat diet with casein or APP, containing the same amount of crude protein. Dietary APP significantly increased gastrocnemius muscle mass (105~110%) after 2, 7 days of feeding, regardless of dietary fat content. Rats were separated into two groups and fed a normal-fat diet with casein or APP. Dietary APP significantly increased gastrocnemius muscle mass (110%) after 56 days of feeding. Dietary APP significantly increased the cross-sectional area of the gastrocnemius skeletal muscle and collagen-rich connective tissue after 7 days of feeding. It decreased the gene expression of Mstn /Myostatin, Trim63 /MuRF1, and Fbxo32 /atrogin-1, but not other gene expression, such as serum IGF-1 after 7 days of feeding. No differences were observed between casein and APP groups with respect to the percentage of Type I, Type IIA, and Type IIX or IIB fibers, as determined by myosin ATPase staining after 7 days of feeding. In the similar experiment, the puromycin-labeled peptides were not different between dietary casein and APP after 2 days of feeding. These results demonstrate that APP induces acute and sustainable skeletal muscle hypertrophy in rats, regardless of dietary fat content. Dietary APP, as a daily protein source, may be an approach for maintaining or increasing muscle mass.

Skeletal muscle is the largest organ in the body and has a broad range of plasticity, undergoing atrophy in response to aging or disease and hypertrophy in response to nutritional supplements or exercise. Loss of skeletal muscle mass and force increases the risk of falls, impairs mobility, and leads to reduced quality of life. In a previous study, we demonstrated that taking in Alaska pollock protein (APP) for only 7 d increased the gastrocnemius muscle mass in rats. This study was conducted to identify hypertrophic myofibers and analyze how hypertrophy occurs within them. Twenty male rats were randomly divided into two groups and administered a diet of casein or APP for 7 d. The expression of each myosin heavy chain (MyHC) isoform in a cross-sectional area was then measured. MyHC IIb and IIx isoforms exhibited hypertrophic features in the gastrocnemius muscles of the APP-fed rats. Furthermore, comprehensive proteomic analyses were conducted to identify changes in protein expression due to muscle hypertrophy. Our results, evaluated by pathway analyses, indicated that the activity of the growth factor signaling pathway was significantly impacted by APP consumption. Moreover, APP could promote protein synthesis by activating the protein kinase B/mechanistic target of the rapamycin signaling pathway, which is also promoted by exercise.

Resin composites employing structural coloration have recently been developed. These resins match to various tooth shades despite being a single paste. To accomplish this, the filler and base resin are tightly bonded, which is thought to provide excellent discoloration resistance. Here, we investigated the surface properties of one of these resins, including the discoloration of the repolished surface. We developed an innovative in vitro method to adjust the repolished surface, in which structural degradation is removed according to scanning electron microscopy (SEM) observation rather than by the naked eye. The resin samples (20 mm (length) × 10 mm (width) × 4 mm (depth)) were manufactured using this resin material. After accelerated aging of the resin by alkaline degradation, the resin was repolished and the discoloration (ΔE*ab), surface roughness (the arithmetic mean roughness (Ra)), and glossiness (the 60° specular) were measured. SEM observation showed that the appearance of the bond between the organic composite filler and base resin on the repolished surface was different from that on the mirror-polished surface. This revealed that according to our in vitro method it was difficult to make the repolished surface structurally identical to the mirror-polished surface. Among the properties of the repolished surface, the degree of discoloration did not change despite the rougher and less glossy surface. It can be concluded that the factors that induce discoloration in this resin composite are independent of the surface roughness and glossiness.

Neurotrophins (NTs) are one of the most characterized neurotrophic factor family members and consist of four members in mammals. Growing evidence suggests that there is a complex inter- and bi-directional relationship between central nervous system (CNS) disorders and cardiac dysfunction, so-called "brain-heart axis". Recent studies suggest that CNS disorders, including neurodegenerative diseases, stroke, and depression, affect cardiovascular function via various mechanisms, such as hypothalamic-pituitary-adrenal axis augmentation. Although this brain-heart axis has been well studied in humans and mice, the involvement of NT signaling in the axis has not been fully investigated. In the first half of this review, we emphasize the importance of NTs not only in the nervous system, but also in the cardiovascular system from the embryonic stage to the adult state. In the second half, we discuss the involvement of NTs in the pathogenesis of cardiovascular diseases, and then examine whether an alteration in NTs could serve as the mediator between neurological disorders and heart dysfunction. The further investigation we propose herein could contribute to finding direct evidence for the involvement of NTs in the axis and new treatment for cardiovascular diseases.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-aged women. Recently, various dietary interventions have been used extensively as a novel therapy against PCOS. In the present study, we show that soy isoflavone metabolites and resistant starch, together with gut microbiota modulations, were successful in decreasing the severity of PCOS-like reproductive features while increasing the expression of gut barrier markers and butyric acid in the gut. In the letrozole-induced PCOS model rats, the intake of both 0.05% soy isoflavones and 11% resistant starch, even with letrozole treatment, reduced the severity of menstrual irregularity and polycystic ovaries with a high concentration of soy isoflavones and equol in plasma. Antibiotic cocktail treatment suppressed soy isoflavone metabolism in the gut and showed no considerable effects on reducing the PCOS-like symptoms. The mRNA expression level of occludin significantly increased with soy isoflavone and resistant starch combined treatment. Bacterial genera such as Blautia , Dorea and Clostridium were positively correlated with menstrual irregularity under resistant starch intake. Moreover, the concentration of butyric acid was elevated by resistant starch intake. In conclusion, we propose that both dietary interventions and gut microbiota modulations could be effectively used in reducing the severity of PCOS reproductive features.

The purpose of this multicenter clinical study was to compare the mid-term clinical effectiveness of direct resin composite restorations using one-step or two-step self-etch adhesives (1-SEAs or 2-SEAs). In total, 352 restorations of class I-V cavities and non-carious cervical lesions in vital teeth (1-SEAs; 52 cases, 2-SEAs; 300 cases) were placed at nine university hospitals and evaluated according to the modified USPHS criteria at baseline, and after 1, 2, and 3 years. The recall rates were 86.6% (1 year), 80.1% (2 years), and 62.2% (3 years). Two restorations failed due to fracture during the follow-up, and there was no significant difference in survival rates between 1-SEAs (97.6%) and 2-SEAs (99.4%). However, 2-SEAs exhibited significantly lower occurrences of discoloration, marginal discoloration, fracture, and plaque retention. Moreover, the subjects reported a significantly lower postoperative hypersensitivity and higher overall satisfaction at all evaluation periods if 2-SEAs were used.

The 20-60 μm axon initial segment (AIS) is proximally located at the interface between the axon and cell body. AIS has characteristic molecular and structural properties regulated by the crucial protein, ankyrin-G. The AIS contains a high density of Na + channels relative to the cell body, which allows low thresholds for the initiation of action potential (AP). Molecular and physiological studies have shown that the AIS is also a key domain for the control of neuronal excitability by homeostatic mechanisms. The AIS has high plasticity in normal developmental processes and pathological activities, such as injury, neurodegeneration, and neurodevelopmental disorders (NDDs). In the first half of this review, we provide an overview of the molecular, structural, and ion-channel characteristics of AIS, AIS regulation through axo-axonic synapses, and axo-glial interactions. In the second half, to understand the relationship between NDDs and AIS, we discuss the activity-dependent plasticity of AIS, the human mutation of AIS regulatory genes, and the pathophysiological role of an abnormal AIS in NDD model animals and patients. We propose that the AIS may provide a potentially valuable structural biomarker in response to abnormal network activity in vivo as well as a new treatment concept at the neural circuit level.

We developed a method to improve protein thermostability, "loop-walking method". Three consecutive positions in 12 loops of Burkholderia cepacia lipase were subjected to random mutagenesis to make 12 libraries. Screening allowed us to identify L7 as a hot-spot loop having an impact on thermostability, and the P233G/L234E/V235M mutant was found from 214 variants in the L7 library. Although a more excellent mutant might be discovered by screening all the 8000 P233X/L234X/V235X mutants, it was difficult to assay all of them. We therefore employed machine learning. Using thermostability data of the 214 mutants, a computational discrimination model was constructed to predict thermostability potentials. Among 7786 combinations ranked in silico, 20 promising candidates were selected and assayed. The P233D/L234P/V235S mutant retained 66% activity after heat treatment at 60 °C for 30 min, which was higher than those of the wild-type enzyme (5%) and the P233G/L234E/V235M mutant (35%).

We performed clinical retrospective study in female cancer patients and fundamental experiments in mice, in order to clarify risk factors for paclitaxel-induced peripheral neuropathy (PIPN). In the clinical study, 131 of 189 female outpatients with cancer undergoing paclitaxel-based chemotherapy met inclusion criteria. Breast cancer survivors (n = 40) showed significantly higher overall PIPN (grades 1-4) incidence than non-breast cancer survivors (n = 91). Multivariate sub-analyses of breast cancer survivors showed that 57 years of age or older and endocrine therapy before paclitaxel treatment were significantly associated with severe PIPN (grades 2-4). The age limit was also significantly correlated with overall development of severe PIPN. In the preclinical study, female mice subjected to ovariectomy received repeated administration of paclitaxel, and mechanical nociceptive threshold was assessed by von Frey test. Ovariectomy aggravated PIPN in the mice, an effect prevented by repeated treatment with 17β-estradiol. Repeated administration of thrombomodulin alfa (TMα), known to prevent chemotherapy-induced peripheral neuropathy in rats and mice, also prevented the development of PIPN in the ovariectomized mice. Collectively, breast cancer survivors, particularly with postmenopausal estrogen decline and/or undergoing endocrine therapy, are considered a PIPN-prone subpopulation, and may require non-hormonal pharmacological intervention for PIPN in which TMα may serve as a major candidate., Competing Interests: Declaration of competing interest Atsufumi Kawabata received a research grant from Asahi Kasei Pharma Corporation. All other authors declare no potential conflicts of interest., (Copyright © 2021 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

This study aims to understand tourists' willingness to pay a price premium for a local green hotel certification, and is one of only a few in the literature for small-island tourism destinations in emerging economies with their unique and pressing sustainability challenges. In a survey of 535 tourists visiting Gili Trawangan, Indonesia, facing numerous waste management and coral reef conservation issues, the willingness to pay extra for sustainable hotel services was elicited. There were five discrete pricing levels across the surveys that ranged from $0.75 USD to $7.50 USD extra per night. We examined the relationship of the respondents' payment choice to their socio-demographic attributes and attitudes regarding environmental issues such as climate change. The main findings and practical implications of the study are: (1) to demonstrate the broad willingness to pay for sustainable hotel services. Findings indicate at all price levels (between $0.75 USD and $7.50 USD), more than 50% of tourists are willing to pay. (2) To estimate a lower bound mean willingness to pay per night for a local green hotel certificate of $1.55USD and 1.34€ EUR, and (3) To identify individual attributes that influence willingness to pay. Findings indicate environmental knowledge and preferences play a role. These results can be used generally to incorporate evidence-based practices into the development of a green hotel marketing strategy, and to help define the target market for small-scale green hotel certification. Additionally, we propose a finance strategy for funding local and sustainable initiatives that support the hotel industry and the island's infrastructure through the premiums collected from the 'Gili Green Award' certificate., Competing Interests: The authors have declared that no competing interests exist.

We developed a method for efficiently activating functional peptides with a large structural contribution using the peptide-searching method with machine learning. The physicochemical properties of the amino acids were employed as variables. As a model peptide, we used GHWYYRCW, which is a functional peptide that inhibits α-amylase derived from human pancreatic juice. First, training data were acquired. A total of 153 peptides were prepared in which 1 amino acid in GHWYYRCW was replaced to construct a 1-amino acid substitution coverage peptide library. The inhibitory activity of each peptide against α-amylase and α-glucosidase was evaluated. Second, random forest (RF) regression analysis was performed using 120 variables, and the enzyme inhibitory activity of the peptide was related to the physicochemical properties. The constructed model had many features describing the charge of the amino acid (isoelectric point and p K 2 ). Then, high inhibitory (HI) peptides were predicted using a library of peptides with 2- or 3-amino acid substitution as test data, which were called HI2 and HI3 peptides. As results, the first or seventh amino acid of the HI2 peptide was replaced with Arg, Trp, or Tyr. We found that all 30 HI2 peptides had significantly higher activity than the original sequence (100%) and 26 of the 30 HI3 peptides were significantly active (86.7%). However, the actual inhibitory activity of the HI3 peptides was improved to a lesser extent. The docking simulation clarified that the CDOCKER energy decrease was roughly correlated with the inhibitory activity. The machine learning-based predictive model was a promising tool for design of substituted peptides with high activity values, and it was assumed that the advanced model that forecasts the interaction index such as the CDOCKER energy substituting for the inhibitory activity would be used to design HI peptides, even in the case of the HI3 peptides.

Remineralization treatment, which offers the advantage of being non-invasive, is increasingly being used as a minimal intervention treatment in managing incipient enamel caries. The aim of this review was to develop EBM guideline for optimized strategies for non-invasive treatment of incipient enamel caries. Japanese Society of Conservative Dentistry (JSCD) guideline committee formulated a Guideline for treating incipient enamel caries using the GRADE system, which is the global, mainstream standard for guideline development. The committee selected the most frequent clinical questions (CQs) in treating incipient enamel caries and identified clinically important outcomes in evaluating the efficacy of treatments. Using extensive electronic and manual searches, relevant randomized controlled trials and controlled clinical trials were identified. Based on evidence profiles produced by the committee, the panel discussed the effects, benefits and disadvantages of the selected treatments, as well as their cost effectiveness and feasibility, in order to achieve a consensus in treating incipient enamel caries non-invasively. A recommendation was made for each clinical question after voting by the panel members. Based on the evidence profile and panel discussions for each CQ, the experts strongly recommended application of topical fluoride to inhibit cavitation of incipient enamel caries, and to diminish white spot lesions., (© 2020 Published by Elsevier Ltd on behalf of The Japanese Association for Dental Science.)

We previously found that equol, a metabolite of intestinal bacterial conversion from soy isoflavone daidzein, has female-specific anorectic effects. In the present study, we used seven-week-old female ovariectomized (OVX) Sprague Dawley rats to test the hypothesis that the anorectic effect of dietary daidzein may be attributed to delayed gastric emptying. Results suggest that dietary daidzein delays gastric emptying and that it has an anorectic effect with residual gastric contents, but not without gastric contents. Dietary equol significantly decreased daily food intake in the OVX rats without sleeve gastrectomy, but not in those with sleeve gastrectomy, suggesting that the accumulation of food in the stomach is required for the anorectic effect of equol to occur. These results support the hypothesis that the anorectic effect of dietary daidzein is attributed to delayed gastric emptying.

The peroxisome is a subcellular organelle that functions in essential metabolic pathways, including biosynthesis of plasmalogens, fatty acid β-oxidation of very-long-chain fatty acids, and degradation of hydrogen peroxide. Peroxisome biogenesis disorders (PBDs) manifest as severe dysfunction in multiple organs, including the central nervous system (CNS), but the pathogenic mechanisms in PBDs are largely unknown. Because CNS integrity is coordinately established and maintained by neural cell interactions, we here investigated whether cell-cell communication is impaired and responsible for the neurological defects associated with PBDs. Results from a noncontact co-culture system consisting of primary hippocampal neurons with glial cells revealed that a peroxisome-deficient astrocytic cell line secretes increased levels of brain-derived neurotrophic factor (BDNF), resulting in axonal branching of the neurons. Of note, the BDNF expression in astrocytes was not affected by defects in plasmalogen biosynthesis and peroxisomal fatty acid β-oxidation in the astrocytes. Instead, we found that cytosolic reductive states caused by a mislocalized catalase in the peroxisome-deficient cells induce the elevation in BDNF secretion. Our results suggest that peroxisome deficiency dysregulates neuronal axogenesis by causing a cytosolic reductive state in astrocytes. We conclude that astrocytic peroxisomes regulate BDNF expression and thereby support neuronal integrity and function., (© 2020 Abe et al.)

Intracranial growing teratoma syndrome (iGTS) is rare phenomenon which is observed in non-germinomatous germ cell tumor (NGGCT) after chemotherapy. The clinical features of iGTS are rapidly increasing in size compared with relapse, no elevation of tumor marker in spite of tumor regrowth, multiple cystic lesions in cranial imaging, and histopathologically diagnosed as mature teratoma. Here we present a 14-year-old man with iGTS which was revealed at 44 months after initial chemotherapy. He was diagnosed as pineal immature teratoma by histopathological specimen, and we performed chemotherapy and radiation therapy. After this treatment, we found growing cystic lesion in tumor removal cavity at 26 months after surgery. The histopathological findings showed dermoid cyst in first salvage surgery. Following this result, we observed him without adjuvant chemotherapy. However he had continuous headache, abnormal eye movement at 44 months after initial treatment. Cranial MRI showed regrowing cyst. In second salvage surgery, mature teratoma was demonstrated on histopathological specimen, and we diagnosed as iGTS. Although most reported iGTSs show rapid increasing after initial chemotherapy, few reported cases show regrowth at chronic phase as our case. In long-term follow-up of germ cell tumor, iGTS is important as differential diagnosis.

Background: Flavonoids form a diverse class of naturally occurring polyphenols ascribed various biological activities, including inhibition of amyloid β (Aβ) fibrillisation and neurotoxicity of relevance to Alzheimer's disease. Cannabis contains a unique subset of prenylated flavonoids, the cannflavins. While selected conventional flavonoids have demonstrated anti-amyloid and neuroprotective potential, any neuroprotective bioactivity of prenylated flavonoids has not been determined. We evaluated the in vitro neuroprotective and anti-aggregative properties of the novel geranylated cannabis-derived flavonoid, cannflavin A against Aβ 1-42 and compared it to two similarly geranylated flavonoids, mimulone and diplacone, to compare the bioactive properties of these unique flavonoids more broadly., Methods: Neuronal viability were assessed in PC12 cells biochemically using the MTT assay in the presence of each flavonoid (1-200 µM) for 48 h. Sub-toxic threshold test concentrations of each flavonoid were then applied to cells, alone or with concomitant incubation with the lipid peroxidant tert-butyl hyrdroperoxide (t-bhp) or amyloid β (Aβ 1-42 ; 0-2 µM). Fluorescent staining was used to indicate effects of Aβ 1-42 on PC12 cellular morphology, while direct effects of each flavonoid on Aβ fibril formation and aggregation were assessed using the Thioflavin T (ThT) fluorometric kinetic assay and transmission electron microscopy (TEM) to visualise fibril and aggregate morphology., Results: Cannflavin A demonstrated intrinsic hormetic effects on cell viability, increasing viability by 40% from 1 to 10 µM but displaying neurotoxicity at higher (>10-100 µM) concentrations. Neither mimulone nor diplacone exhibited such a biphasic effect, instead showing only concentration-dependent neurotoxicity, with diplacone the more potent (from >1 µM). However at the lower concentrations (<10 µM), cannflavin A increased cell viability by up to 40%, while 10 µM cannflavin A inhibited the neurotoxicity elicited by Aβ 1-42 (0-2 µM), reducing Aβ aggregate adherence to PC-12 cells and associated neurite loss. The neuroprotective effects of cannflavin A were associated with a direct inhibition of Aβ 1-42 fibril and aggregate density, evidenced by attenuated ThT fluorescence kinetics and microscopic evidence of both altered and diminished density of Aβ aggregate and fibril morphology via electron microscopy., Conclusions: These findings highlight a concentration-dependent hormetic and neuroprotective role of cannflavin A against Aβ-mediated neurotoxicity, associated with an inhibition of Aβ fibrillisation. The efficacy of the cannabis flavone may itself direct further lead development targeting neurodegeneration in Alzheimer's disease. However, the geranylated flavonoids generally displayed a comparatively potent neurotoxicity not observed with many conventional flavonoids in vitro., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Silicon micropore optics using deep reactive ion etching of silicon wafers has been being developed for future x-ray astronomy missions. Sidewalls of the micropores through a thin wafer with a typical thickness of hundreds of micrometers and a pore width of ∼20  μm are used for x-ray mirrors. However, burr structures observed after etching with a typical height of a few micrometers at the micropore edges are known to significantly reduce x-ray reflectivity. A new grinding and chemical mechanical polishing process is introduced to remove the burr structures. Both sides of the silicon wafer were ground and precisely polished after etching. X-ray reflectivity measurements confirmed an increase of reflectivity by 2-15 times at incident angles of 0.8-0.2 deg. The surface microroughness worsened from 2.0±0.2  nm rms to 7.8-0.8+0.6  nm rms; however, an additional annealing recovered the smooth surface and the estimated surface microroughness was <1.4  nm rms. This new process enables not only removing the burr structures but also choosing a flat part of the sidewalls for better angular resolution.

The promotion of muscle recovery after immobilization is important to preserve an optimum health status. Here, we examined the effect of dietary Alaska pollack protein (APP) on skeletal muscle weight after atrophy induced by hind limb immobilization using plaster immobilization technique. Rat left limb was casted with a wetted plaster cast under anesthesia. After 2 weeks of feeding, the cast was removed and the rats were divided into three groups, namely, a baseline group, high-fat casein diet group, and high-fat APP diet group. After 3 weeks of feeding, the skeletal muscles (soleus, extensor digitorum longus [EDL], and gastrocnemius) were sampled. The estimated weight gains of soleus, gastrocnemius, and EDL muscle in the immobilized limbs were significantly larger in the rats fed with APP diet as compared with those fed with casein diet. In soleus muscle, dietary APP increased the expression of Igf1 and Myog genes in the immobilized limbs after the recovery period., Competing Interests: This study was funded by Nippon Suisan Kaisha, Ltd. FK and KH are former employees of Nippon Suisan Kaisha, Ltd., and KU is a current employee of Nippon Suisan Kaisha, Ltd. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Ecosystems and biodiversity produce benefits to society, but many of them are hard to quantify. For example, it is unclear whether European societies gain benefits from experiencing rivers that host high native biodiversity. Without such knowledge, monetary investments into ecologically oriented river management plans are difficult to justify. The objective of this study was to reveal how the public in four European countries values ecological characteristics of domestic rivers and the outcomes of hypothetical river basin management plans designed to improve river ecosystems, particularly fish biodiversity. We conducted a choice experiment among the populations in Norway, Sweden, Germany, and France. We found similar preference structures in all countries with high marginal willingness-to-pay for improvements of abiotic river attributes (increased accessiblity of the river banks, improved bathing water quality, decreased river fragmentation). Citizens also benefited from certain fish species occurring in a river with native salmonid species being more valued than nonnatives, particularly in Norway, and from the degree of a river's native biodiversity. Welfare measures calculated for selected river basin management plans (policy scenarios) revealed societal benefits that were primarily derived from ecological river management whereas a scenario focusing on hydroelectricity production generated the lowest utility. We conclude that ecological river management may produce high nonmarket economic benefits in all study countries, particularly through the management of abiotic river attributes and the restoration of declining or extinct fish species. Our results help to inform decisions on restoration efforts by showcasing the benefits that these measures have for the public.

Neurons of the parabrachial nucleus (PB) receive nociceptive input from the dorsal horn (DH) of the spinal cord and caudal part of the spinal trigeminal nucleus (Vc). Previously, we demonstrated that glutamatergic lateral PB neurons innervate orexin (ORX) neurons in the perifornical area (PeF) of the hypothalamus. However, the neural circuit via which ORX neurons receive nociceptive input from the DH and brainstem remains to be determined. In the present study, we aimed to clarify the potential nociceptive circuit from DH/Vc to PeF via lateral PB. We first examined the neuronal activity of fluorogold (FG)-labeled, PeF-projecting lateral PB neurons in Wistar rats following either saline or formalin injection to the forepaw or lips. We clearly detected more abundant c-Fos-positive, FG-labeled neurons in the PB nucleus. To investigate the relay from the DH/Vc to the PeF via the lateral PB, we injected FG into the PeF and biotinylated dextranamine (BDA) into the contralateral DH or ipsilateral Vc. We observed the most prominent overlap between BDA-labeled axon terminals and FG-labeled neurons in the dorsal lateral and central lateral subnuclei. Furthermore, we found that FG-labeled neurons formed close contact sites with BDA-labeled axons with synaptophysin immunoreactivity. Using electron microscopy, we confirmed that these contact sites were truly synapses. Taken together, our results indicate that the DH/Vc transmits nociceptive information to the PeF via the lateral PB, suggesting the involvement of ORX neurons in the pain pathway., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective and Background: Survival predictions by subjective evaluations are important for end-stage patients. However, subjective evaluations based on experience are difficult. Therefore, we investigated whether the Glasgow prognostic score (GPS), prognostic nutritional index (PNI), and C-reactive protein (CRP)/albumin ratio (CRP/Alb ratio) calculated from the laboratory values of objective evaluations are useful for predicting survival times in end-stage patients. Methods: We retrospectively investigated the age, sex, death cause, CRP levels, Alb levels, and lymphocyte counts in 363 cancer and noncancer patients who died in the 12-month period between April 2015 and March 2016. A multivariate analysis was performed to calculate GPS, PNI, and the CRP/Alb ratio from laboratory values and adjusted for confounding factors. Results: PNI and CRP/Alb ratio exhibited negative and positive correlations with survival days, respectively. All GPS, PNI, and CRP/Alb ratio were useful to predict two to four remaining weeks. Interestingly, CRP/Alb ratio, but not GPS or PNI, was higher in patients with predicted short-term survival of zero to two weeks than in that of two to four weeks (odds ratio 2.32; 95% confidence interval 1.61-3.34). Discussion: These results suggest that the CRP/Alb ratio is an independent factor that is beneficial to predict short-term survival of within two weeks.

Orexin (ORX) neurons in the hypothalamus send their axons to arousal-promoting areas. We have previously shown that glutamatergic neurons in the lateral parabrachial nucleus (LPB) innervate ORX neurons. In this study, we examined potential pathways from the LPB to ORX neurons projecting to arousal-promoting areas in the brainstem by a combination of tract-tracing techniques in male Wistar rats. We injected the anterograde tracer biotinylated dextranamine (BDA) into the LPB and the retrograde tracer cholera toxin B subunit (CTb) into the ventral tegmental area, dorsal raphe nucleus, pedunculopontine tegmental nucleus, laterodorsal tegmental area, or locus coeruleus (LC). We then analyzed the BDA-labeled fibers and ORX-immunoreactive neurons in the hypothalamus. We found that double-labeled ORX and CTb neurons were the most abundant after CTb was injected into the LC. We also observed prominently overlapping distribution of BDA-labeled fibers, arising from neurons located in the lateral-most part of the dorsomedial nucleus and adjacent dorsal perifornical area. In these areas, we confirmed by confocal microscopy that BDA-labeled synaptophysin-immunoreactive axon terminals were in contiguity with cell bodies and dendrites of CTb-labeled ORX-immunoreactive neurons. These results suggest that the LPB innervates arousal-promoting areas via ORX neurons and is likely to promote arousal responses to stimuli.

Public support for biodiversity conservation is shaped by people's values and their knowledge, beliefs, and attitudes toward the environment. We conducted the first multinational representative survey of the general public's perceptions of river fish biodiversity in France, Germany, Norway, and Sweden. For the online survey, 1000 respondents per country were randomly selected from large panels following country-specific quotas set on age, gender, and educational level. Questions covered people's level of knowledge, beliefs, values, and attitudes toward river fish, environmental threats, and conservation measures. We found that the public had limited knowledge of freshwater fishes. Two non-native species, rainbow trout (Oncorhynchus mykiss) and brook trout (Salvelinus fontinalis), were widely perceived as native, whereas native Atlantic salmon (Salmo salar) was mostly classified as native in Scandinavia and largely as non-native in central Europe. These results suggest an extinction of experience paralleling the extirpation or decline of salmon stocks in countries such as Germany and France. Respondents thought pollution was the dominant threat to riverine fish biodiversity. In reality, habitat loss, dams, and the spread of non-native fishes are equally important. Despite limited biological knowledge, respondents from all countries held an overwhelmingly proecological worldview, supported conservation stocking, and appreciated native fishes, although only a minority interacted with them directly. Differences among the 4 countries related to several conservation issues. For example, threats to biodiversity stemming from aquaculture were perceived as more prevalent in Norway compared with the other 3 countries. Promoting fish conservation based on charismatic species and use values of fishes may work well in countries with a strong economic and cultural link to the freshwater environment, such as Norway. In countries where people rather abstractly care for nature, focusing conservation messaging on broader ecosystem traits and non-use values of fishes is likely to win more support., (© 2018 Society for Conservation Biology.)

We previously found that daidzein decreased food intake in female rats. To understand the mechanism of anorectic action of dietary daidzein, it is necessary to determine distributions of daidzein and S-equol, a metabolite of intestinal bacterial conversion from daidzein, in the body. In the present study, we measured the concentrations of daidzein and S-equol in serum and bile in sham-operated and ovariectomized female rats fed a diet containing 150 mg/kg daidzein for 7 days. Dietary daidzein increased serum and bile concentrations of S-equol to far higher levels than those of daidzein. S-equol concentration was more than several hundred fold-higher in bile than in serum, regardless of ovariectomy. Moreover, to investigate whether accumulation of S-equol is facilitated by efficient enterohepatic circulation during continuous intake of daidzein and S-equol, female rats were fed diet containing daidzein or S-equol (both 150 mg/kg), or control diet for 1, 2, 3, or 5 days. Dietary daidzein significantly increased serum and bile concentrations of S-equol in a time-dependent manner, but not those of daidzein. These results indicated that substantial proportion of dietary daidzein was converted to S-equol, which underwent efficient enterohepatic circulation and predominantly accumulated there.

Alaska pollack protein (APP) was previously shown to reduce serum triacylglycerol and the atherogenic index and significantly increase gastrocnemius muscle mass in rats. To determine which myofibers are involved in this observed hypertrophy, we stained the gastrocnemius muscle with fast and slow fiber-specific antibodies and measured the muscle fiber diameter. We observed muscle hypertrophy in both the fast and slow fibers of APP-fed rats. Although muscle hypertrophy leads to drastic lipid changes, the amount of lipids did not differ significantly between casein-fed and APP-fed rats. To determine the lipid changes at the molecular species level and their localization, we performed matrix-assisted laser desorption/ionization mass spectrometry imaging to visualize lipids in the gastrocnemius muscles. We determined that lipid molecules were significantly changed due to APP feeding. Thus, APP feeding changes muscle lipid metabolism, and these metabolic changes might be related to hypertrophy.

Peroxisome biogenesis disorders (PBDs) manifest as neurological deficits in the central nervous system, including neuronal migration defects and abnormal cerebellum development. However, the mechanisms underlying pathogenesis remain enigmatic. Here, to investigate how peroxisome deficiency causes neurological defects of PBDs, we established a new PBD model mouse defective in peroxisome assembly factor Pex14p, termed Pex14 ΔC/ΔC mouse. Pex14 ΔC/ΔC mouse manifests a severe symptom such as disorganization of cortical laminar structure and dies shortly after birth, although peroxisomal biogenesis and metabolism are partially defective. The Pex14 ΔC/ΔC mouse also shows malformation of the cerebellum including the impaired dendritic development of Purkinje cells. Moreover, extracellular signal-regulated kinase and AKT signaling are attenuated in this mutant mouse by an elevated level of brain-derived neurotrophic factor (BDNF) together with the enhanced expression of TrkB-T1, a dominant-negative isoform of the BDNF receptor. Our results suggest that dysregulation of the BDNF-TrkB pathway, an essential signaling for cerebellar morphogenesis, gives rise to the pathogenesis of the cerebellum in PBDs., Competing Interests: The authors declare no competing financial interests.

We fabricated a silicon micropore optic using deep reactive ion etching and coated by Pt with atomic layer deposition (ALD). We confirmed that a metal/metal oxide bilayer of Al 2 O 3 ∼10  nm and Pt ∼20  nm was successfully deposited on the micropores whose width and depth are 20 μm and 300 μm, respectively. An increase of surface roughness of sidewalls of the micropores was observed with a transmission electron microscope and an atomic force microscope. X-ray reflectivity with an Al Kα line at 1.49 keV before and after the deposition was measured and compared to ray-tracing simulations. The surface roughness of the sidewalls was estimated to increase from 1.6±0.2  nm rms to 2.2±0.2  nm rms. This result is consistent with the microscope measurements. Post annealing of the Pt-coated optic at 1000°C for 2 h showed a sign of reduced surface roughness and better angular resolution. To reduce the surface roughness, possible methods such as the annealing after deposition and a plasma-enhanced ALD are discussed.

Coastal areas are under increasing pressure from rapid human population growth, yet empirical research on the effect of migration on coastal and marine resources is scarce. We contribute to this understudied literature by conducting an original household survey in a coastal region of Southeastern Ghana. This study employs two proxies for pro-environmental behavior that have not, to our knowledge, been used in the context of coastal migration, to explicitly compare migrant and non-migrant populations. Environmental attitudes toward coastal resources and individual extraction behavior in common-pool resource (CPR) experiments have shown broad relevance in the literature to understand natural resource decision making. We found that migrants in general did not differ significantly from non-migrants in relation to their environmental attitudes or their extraction behavior in the CPR game. However, when focusing on migrant fishers only, results suggested that this subgroup was less concerned about the utilization of coastal resources than non-migrant fishers and behaved less cooperatively in the CPR experiment. These findings, though, held true only for the subgroup of fishers, and could not be found for other occupational groups. Therefore, we conclude that migrants do not per se value coastal resources less or cooperate less in CPR situations, but that socioeconomic characteristics, and particularly their occupational status and their relation to the resource, matter., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

This study was conducted to investigate the distribution of rotavirus genotypes in Nara Prefecture, Japan before and after the introduction of rotavirus vaccination in 2011. Since the 2011/2012 season, DS-1-like G1P[8] strains have been detected in Nara Prefecture, accounting for about half of all strains in the 2014/2015 season. During the 2015/2016 season, no DS-1-like G1P[8] strains were detected; G2P[4] was the predominant genotype.

The p53 family member p73 plays a critical role in brain development. p73 knockout mice exhibit a number of deficits in the nervous system, such as neuronal death, hydrocephalus, hippocampal dysgenesis, and pheromonal defects. Among these phenotypes, the mechanisms of hydrocephalus remain unknown. In this study, we generated a p73 knock-in (KI) mutant mouse and a conditional p73 knockout mouse. The homozygous KI mutants showed aqueductal stenosis. p73 was expressed in the ependymal cell layer and several brain areas. Unexpectedly, when p73 was disrupted during the postnatal period, animals showed aqueductal stenosis at a later stage but not hydrocephalus. An assessment of the integrity of cilia and basal body (BB) patch formation suggests that p73 is required to establish translational polarity but not to establish rotational polarity or the planar polarization of BB patches. Deletion of p73 in adult ependymal cells did not affect the maintenance of translational polarity. These results suggest that the loss of p73 during the embryonic period is critical for hydrocephalus development.

We compared the effects of two major isoflavones, daidzein and genistein, on lipid metabolism in rats. Daidzein (150 mg/kg diet), genistein (150 mg/kg diet), daidzein and genistein (1:1, 300 mg/kg diet), or control diets were fed to 4 groups of 6-week-old ovariectomized (Ovx) and non-Ovx Sprague Dawley rats for 4 weeks. Dietary daidzein, but not genistein, reduced serum and hepatic total cholesterol levels significantly relative to that by the control group, regardless of whether the rats had undergone ovariectomy. Genistein did not exhibit any physiological effects on lipid levels, but did affect genes involved in cholesterol metabolism. These results indicate that daidzein and genistein may influence lipid regulation via differing modes of action.

Neural stem cells (NSCs) are multipotent and are considered ideal source for regenerating damaged neural cells for neurological disorders. During culture of NSCs, both the measurement and the evaluation of their differentiation potential are important to maintain stable quality-assured NSCs for regenerative treatments since the rate of differentiation into certain lineages from NSCs is still not fully controllable. However, conventional cell evaluation techniques using biological molecular are still invasive, costly, and time-consuming. Therefore, a non-invasive, low-cost, and rapid cell evaluation method is required to expand the possibilities of regenerative therapy, especially in the facilities that produce cells for therapy. To address these such technological limitations in non-invasive cell evaluation, we propose the efficacy of computer-aided morphology-based prediction of potentials of stem cells by using multiple and time-course morphological parameters from phase-contrast microscopic images combined with experimentally determined differentiation potentials. In this work, we quantified the morphological parameters of NSCs during three types of differentiation culture and investigated two applications with NSCs: (i) evaluation of their differentiation type and (ii) early prediction of neural differentiation rate. Our data demonstrate that it is possible to non-invasively evaluate neural differentiation types and quantitatively predict future differentiation rates by using morphological information from the first 4 days. Our findings indicate the potential application of morphology-based non-invasive evaluation for optimizing effective differentiation protocols, screening of compounds to mediate NSC differentiation, and quality maintenance of regenerative medicine products., (Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Background: Mesonephric adenocarcinoma (MA) is a rare tumor believed to arise from mesonephric remnants occurring mostly in the uterine cervix and, to a lesser extent, the corpus. Since the first case report of MA in the corpus in 1995, only 16 cases have been reported in the English literature. A recent report suggested that MA originates in Müllerian tissue and exhibits the mesonephric differentiation phenotype., Case Presentation: An asymptomatic 61-year-old woman was referred to our hospital because of elevated levels of tumor markers. Imaging revealed an intramural lesion of the uterine corpus exhibiting fluorodeoxyglucose uptake. A total hysterectomy and bilateral salpingo-oophorectomy were performed. The tumor was completely confined to the corpus wall and was composed of an intracystic bulky component and an invasive component in the myometrial layer. The tumor exhibited a variety of growth patterns, including a characteristic tubular pattern with dense eosinophilic secretion reminiscent of the thyroid, as well as a variety of morphologies, such as acinar, papillary, and ductal structures. The structures were immunoreactive for CK7, vimentin, CD10, calretinin, PAX8, and GATA3 and almost completely negative for ER/PgR. CA125 and CA19-9 antigen expression was also detected., Conclusion: A case of MA with a unique growth pattern of an intracystic mass within the corpus wall is presented. The histogenesis and differential diagnoses are discussed. The histogenesis of MA is not yet clear. We hypothesize two different pathways involved: 1) direct development from the mesonephric remnants and/or 2) mesonephric transformation of Müllerian adenocarcinoma.

We evaluated the effects of difructose anhydride III (DFAIII) on body weights of ovariectomized rats, which are a good model for obesity by estrogen deficiency-induced overeating. Female rats (10 weeks old) were subjected to ovariectomy or sham operation and then fed with or without a diet containing 3% or 6% DFAIII for 33 days or pair-fed control diet during the same period. Rats fed DFAIII showed significantly decreased food intake, energy intake, body weight gain, body energy accumulation, and fat tissue weight than control group, regardless of ovariectomy. DFAIII may decrease body fat dependent of reduced food/energy intake. Compared with the respective pair feeding groups, rats fed DFAIII showed significantly decreased body energy and fat tissue weight, regardless of ovariectomy, suggesting its potential as a low-energy substitute for high-energy sweeteners. The low energy of DFAIII may contribute to decreased body fat, which may not be dependent on obesity.

Resolving uncertainties in managed social-ecological systems requires adaptive experimentation at whole-ecosystem levels. However, whether participatory adaptive management fosters ecological understanding among stakeholders beyond the sphere of science is unknown. We experimentally involved members of German angling clubs ( n = 181 in workshops, n = 2483 in total) engaged in self-governance of freshwater fisheries resources in a large-scale ecological experiment of active adaptive management of fish stocking, which constitutes a controversial management practice for biodiversity and ecosystem functioning when conducted inappropriately. The collaborative ecological experiments spanned several years and manipulated fish densities in 24 lakes with two species. In parallel, we experimentally compared changes in ecological knowledge and antecedents of proenvironmental behavior in stakeholders and managers who were members of a participatory adaptive management treatment group, with those receiving only a standard lecture, relative to placebo controls. Using a within-subjects pretest-posttest control design, changes in ecological knowledge, environmental beliefs, attitudes, norms, and behavioral intentions were evaluated. Participants in adaptive management retained more knowledge of ecological topics after a period of 8 months compared to those receiving a standard lecture, both relative to controls. Involvement in adaptive management was also the only treatment that altered personal norms and beliefs related to stocking. Critically, only the stakeholders who participated in adaptive management reduced their behavioral intentions to engage in fish stocking in the future. Adaptive management is essential for robust ecological knowledge, and we show that involving stakeholders in adaptive management experiments is a powerful tool to enhance ecological literacy and build environmental capacity to move toward sustainability.

Cortical neurogenesis is a fundamental process of brain development that is spatiotemporally regulated by both intrinsic and extrinsic cues. Although recent evidence has highlighted the significance of transcription factors in cortical neurogenesis, little is known regarding the role of RNA-binding proteins (RBPs) in the post-transcriptional regulation of cortical neurogenesis. Here, we report that meiosis arrest female 1 (MARF1) is an RBP that is expressed during neuronal differentiation. Cortical neurons expressed the somatic form of MARF1 (sMARF1) but not the oocyte form (oMARF1). sMARF1 was enriched in embryonic brains, and its expression level decreased as brain development progressed. Overexpression of sMARF1 in E12.5 neuronal progenitor cells promoted neuronal differentiation, whereas sMARF1 knockdown decreased neuronal progenitor differentiation in vitro. We also examined the function of sMARF1 in vivo using an in utero electroporation technique. Overexpression of sMARF1 increased neuronal differentiation, whereas knockdown of sMARF1 inhibited differentiation in vivo. Moreover, using an RNase domain deletion mutant of sMARF1, we showed that the RNase domain is required for the effects of sMARF1 on cortical neurogenesis in vitro. Our results further elucidate the mechanisms of post-transcriptional regulation of cortical neurogenesis by RBPs.

The current study elucidated the epidemiological characteristics of sapovirus (SaV) and human astrovirus (HAstV) associated with gastroenteritis among children in regional populations of Nara Prefecture, Japan, during the 2009/2010-2014/2015 seasons. The SaV detection rate was 7.5% (71/948) according to reverse transcription-polymerase chain reaction. A high SaV detection rate of 13.5% was observed among children 4 years of age. The highest SaV detection rate was observed in June (19.2%), followed by July (11.1%). The detected SaV included 7 genotypes: GI.1, GI.2, GII.3, GII.1, GI.3, GII.2, and GV, in order of decreasing prevalence. In comparison, the HAstV detection rate was 4.2% (40/948). The HAstV detection rate among children 4 years of age was 12.2%. The HAstV detection rate was highest in July (13.9%), followed by May (10.5%) and August (6.7%). The detected HAstVs included genotypes 1, 4, 6, and 8. The most prevalent genotype was 1, followed by 4 and 8. This report provides an epidemiological overview of SaV and HAstV infection in Nara Prefecture, Japan.

To assess the effect of dienogest on recurrence of ovarian endometriomas and severity of pain after laparoscopic surgery, a retrospective study of 81 patients was performed at three institutions in Osaka, Japan. Patients had a six-month minimum follow-up after laparoscopic surgery for ovarian endometriomas performed between June 2012 and August 2014. Patients who chose to receive 2 mg dienogest daily and those who were managed expectantly postoperatively were included. Recurrence was defined as the presence of endometriomas of more than 2 cm. A visual analog scale (VAS) was used to score the intensity of pelvic pain. The cumulative recurrence rate and absolute VAS score changes between the baseline and at 6, 12, 18 and 24 months after the start of administration were evaluated in both groups. The recurrence rate was 16.5% and 24.0% in the expectant management group at 12 and 24 months, respectively. No recurrences occurred in the dienogest treatment group. The rate of VAS score reduction was significantly higher in the dienogest than in the expectant management group. Dienogest is effective on the recurrence of ovarian endometrioma and relieving pelvic pain after laparoscopic surgery.

Chondroitin sulfate proteoglycans (CSPGs) are a major component of glial scars, inhibiting axonal growth in the central nervous system. Protein tyrosine phosphatase, receptor type S (PTPσ) has been identified as a receptor for CSPGs, whereas its downstream signaling pathway remains to be fully understood. Here, we report that nucleoside diphosphate kinase 2 (NME2) interacts with PTPσ. We screened proteins associated with PTPσ by mass spectrometry, and obtained NME2. Immunoprecipitation analysis revealed that NME2 associated with the PTPσ intracellular domain in HEK-293T cells. NME2 was expressed in the cytoplasm and nucleus of cortical neurons, and knockdown of NME2 in the cortical neurons completely rescued neurite outgrowth inhibition induced by CSPGs. These results demonstrate that NME2 associates with PTPσ to elicit neurite outgrowth inhibition in response to CSPGs., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The combined activation of the cellular energy sensor AMP-activated protein kinase (AMPK) and the nuclear transcription factor peroxisome proliferator-activated receptor delta (PPARδ) has been demonstrated to improve endurance and muscle function by mimicking the effects of exercise training. However, their combined pharmacological activation with exercise training has not been explored. Balb/c mice were trained on a treadmill and administered both the AMPK activator AICAR and the PPARδ agonist GW0742 for 4 weeks. AICAR treatment potentiated endurance, but the combination of AICAR and GW0742 further potentiated endurance and increased all running parameters significantly relative to exercised and nonexercised groups (138-179% and 355% increase in running time, respectively). Despite the lack of change in basal whole-body metabolism, a significant shift to fat as the main energy source with a decline in carbohydrate utilization was observed upon indirect calorimetry analysis at the period near exhaustion. Increased energy substrates before exercise, and elevated muscle nonesterified fatty acids (NEFA) and elevated muscle glycogen at exhaustion were observed together with increased PDK4 mRNA expression. Citrate synthase activity was elevated in AICAR-treated groups, while PGC-1α protein level tended to be increased in GW0742-treated groups. At exhaustion, Pgc1a was robustly upregulated together with Pdk4, Cd36, and Lpl in the muscle. A robust upregulation of Pgc1a and a downregulation in Chrebp were observed in the liver. Our data show that combined pharmacological activation of AMPK and PPARδ potentiates endurance in trained mice by transcriptional changes in muscle and liver, increased available energy substrates, delayed hypoglycemia through glycogen sparing accompanied by increased NEFA availability, and improved substrate shift from carbohydrate to fat., (© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

We investigated the effect of daidzein feeding and estradiol treatment on food intake in cholecystokinin-1 receptor (CCK1R) deficiency, leptin receptor (ObRb) deficiency rats and their wild-type rats. These rats underwent an ovariectomy or a sham operation. For the 5 week experiment, each rat was divided in three groups: control, daidzein (150 mg/kg diet), and estradiol (4.2 μg/rat/day) groups. In both CCK1R+ and CCK1R- rats, daidzein feeding and estradiol treatment significantly decreased food intake. Daidzein feeding significantly reduced food intake in ovariectomized ObRb- rats, although not in ObRb+ rats. Estradiol treatment significantly lowered food intake in ovariectomized ObRb+ and ObRb- rats. In the ovariectomized rats, estradiol treatment significantly increases uterine weight, while daidzein feeding did not change it, suggesting that daidzein might have no or weak estrogenic effect in our experiment. These results suggest that CCK1R and ObRb signalings were not essential for the daidzein- and estradiol-induced anorectic action.

High-fat foods tend to be palatable and can cause addiction in mice via a reinforcing effect. However, mice showed preference for low fat concentrations that do not elicit a reinforcing effect in a two-bottle choice test with water as the alternative. This behavior indicates the possibility that the mechanism underlying fat palatability may differ depending on the dietary fat content. To address this issue, we examined the influences of the opioid system and olfactory and gustatory transductions on the intake and reinforcing effects of various concentrations of a dietary fat emulsion (Intralipid). We found that the intake and reinforcing effects of fat emulsion were reduced by the administration of an opioid receptor antagonist (naltrexone). Furthermore, the action of naltrexone was only observed at higher concentrations of fat emulsion. The intake and the reinforcing effects of fat emulsion were also reduced by olfactory and glossopharyngeal nerve transections (designated ONX and GLX, respectively). In contrast to naltrexone, the effects of ONX and GLX were mainly observed at lower concentrations of fat emulsion. These results imply that the opioid system seems to have a greater role in determining the palatability of high-fat foods unlike the contribution of olfactory and glossopharyngeal nerves.

We previously found that daidzein decreased food intake in female rats. The present study aimed to elucidate the relationship between dynamics of appetite-mediated neuropeptides and the anorectic effect of daidzein. We examined appetite-mediated gene expression in the hypothalamus and small intestine during the 3 meals per day feeding method. Daidzein had an anorectic effect specifically at the second feeding. Neuropeptide-Y (NPY) and galanin mRNA levels in the hypothalamus were significantly higher after feeding in the control but not in the daidzein group, suggesting that daidzein attenuated the postprandial increase in NPY and galanin expression. The daidzein group had higher corticotrophin-releasing hormone (CRH) mRNA levels in the hypothalamus after feeding, and increased cholelcystokinin (CCK) mRNA levels in the small intestine, suggesting that CCK is involved in the hypothalamic regulation of this　anorectic effect. Therefore, daidzein may induce anorexia by suppressing expression of NPY and galanin and increasing expression of CRH in the hypothalamus.

Neuronal migration is a crucial process in the organization of the developing cerebral cortex. Although a number of positive regulatory mechanisms of radial migration have been identified, negative cell-autonomous mechanisms have yet to be fully described. Here we report a newly identified Migration Inhibitory Protein (MINP, formerly known as 2900011O08Rik) that negatively regulates radial migration. MINP mRNA was specifically detected in the central and peripheral nervous system, and especially enriched in the cerebral cortex. MINP immunoreactivity co-localized with the neuronal marker Tuj1 and was detected in the cytoplasm of post-mitotic neurons. To elucidate the function of MINP in the developing brain, we performed in utero electroporation of MINP siRNA, MINP shRNA, or MINP-overexpressing vectors into mouse cortices and carried out in vivo migration assays. Whereas knockdown of MINP did not alter neuronal morphology, the radial migration was found accelerated by MINP knockdown, and reduced by MINP overexpression. This migration phenotype was also confirmed in vitro, indicating that MINP regulates neuronal migration in a cell-autonomous fashion. Furthermore, downregulation of MINP affected microtubule stability by interacting with tubulin that is a potential mechanism involved in the regulation of neuronal migration.

Fatty acids (FA) are an important energy source during exercise. In addition to its role as an energy supply for skeletal muscle, FA may activate signaling pathways that regulate gene expression. FA translocase/cluster of differentiation 36 (CD36) and G protein-coupled receptor GPR120 are long-chain FA receptors. In this study, we investigated the impact of CD36 or GPR120 deletion on energy metabolism during exercise. CD36 has been reported to facilitate cellular transport and oxidation of FA during endurance exercise. We show that CD36 deletion decreased exogenous FA oxidation during exercise, using a combination of (13)C-labeled FA oxidation measurement and indirect calorimetry. In contrast, GPR120 deletion had no observable effect on energy metabolism during exercise. Our results further substantiate that CD36-mediated FA transport plays an essential role in efficient FA oxidation during exercise.

The mechanisms that regulate the establishment of adult stem cell pools during normal and perturbed mammalian development are still largely unknown. Here, we asked whether a maternal cytokine surge, which occurs during human maternal infections and has been implicated in cognitive disorders, might have long-lasting consequences for neural stem cell pools in adult progeny. We show that transient, maternally administered interleukin-6 (IL-6) resulted in an expanded adult forebrain neural precursor pool and perturbed olfactory neurogenesis in offspring months after fetal exposure. This increase is likely the long-term consequence of acute hyperactivation of an endogenous autocrine/paracrine IL-6-dependent self-renewal pathway that normally regulates the number of forebrain neural precursors. These studies therefore identify an IL-6-dependent neural stem cell self-renewal pathway in vivo, and support a model in which transiently increased maternal cytokines can act through this pathway in offspring to deregulate neural precursor biology from embryogenesis throughout life., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Obtaining a homogenous population of central nervous system neurons has been a significant challenge in neuroscience research; however, a recent study established a retinoic acid-treated embryoid bodies-based differentiation protocol that permits the effective generation of highly homogeneous glutamatergic cortical pyramidal neurons from embryonic stem cells. We were able to reproduce this protocol regarding the purity of glutamatergic neurons, but these neurons were not sufficiently healthy for long-term observation under the same conditions that were originally described. Here, we achieved a substantial improvement in cell survival by applying a simple technique: We changed the medium for glutamatergic neurons from the original complete medium to commercially available SBM (the Nerve-Cell Culture Medium manufactured by Sumitomo Bakelite Co. Ltd.) and finally succeeded in maintaining healthy neurons for at least 3 weeks without decreasing their purity. Because SBM contains glial conditioned medium, we postulated that brain-derived neurotrophic factor or basic fibroblast growth factor is the key components responsible for pro-survival effect of SBM on neurons, and examined their effects by adding them to CM. As a result, neither of them had pro-survival effect on pure glutamatergic neuronal population., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Moderate-intensity running (treadmill velocity of 21 m/min) increased blood lactate and actived transforming growth factor-β (TGF-β) concentration in rat cerebrospinal fluid (CSF). On the other hand, low-intensity running (15 m/min) did not increase blood lactate and caused no change in CSF TGF-β. Intraperitoneal (i.p.) administration of lactate to anesthetized rats caused an increase in blood lactate similar to that observed after a 21 m/min running exercise and increased the level of active TGF-β in CSF. Intraperitoneal administration of lactate at the same dose to awake and unrestricted rats caused a decrease in the respiratory exchange ratio, that is, enhancement of fatty acid oxidation and depression of spontaneous motor activity (SMA). Given that intracisternal administration of TGF-β to rats has been reported to enhance fatty acid metabolism and to depress SMA, we surmise that the observed changes caused by i.p. lactate administration in this study were mediated, at least in part, by TGF-β in the brain.