Reward and reinforcement activity in the nucleus accumbens during learning

The nucleus accumbens core (NAcc) has been implicated in learning associations between sensory cues and profitable motor responses. However, the precise mechanisms that underlie these functions remain unclear. We recorded single-neuron activity from the NAcc of primates trained to perform a visual-motor associative learning task. During learning, we found two distinct classes of NAcc neurons. The first class demonstrated progressive increases in firing rates at the go-cue, feedback/tone and reward epochs of the task, as novel associations were learned. This suggests that these neurons may play a role in the exploitation of rewarding behaviors. In contrast, the second class exhibited attenuated firing rates, but only at the reward epoch of the task. These findings suggest that some NAcc neurons play a role in reward-based reinforcement during learning

社会経済的地位と消化器がんの関係について : 症例対照研究

Although socioeconomic status (SES) has been associated with cancer risk, little research on this association has been done in Japan. To evaluate the association between SES and digestive tract cancer risk, we conducted a case-control study for head and neck, esophageal, stomach, and colorectal cancers in 3188 cases and the same number of age- and sex-matched controls within the framework of the Hospital-based Epidemiological Research Program at Aichi Cancer Center III (HERPACC III). We employed the education level and areal deprivation index (ADI) as SES indicators. The association was evaluated with odds ratios (ORs) and 95% confidence intervals (CIs) by conditional logistic models adjusted for potential confounders. Even after allowance for known cancer risk factors, the education level showed linear inverse associations with head and neck, stomach, and colorectal cancers. Compared to those educated to junior high school, those with higher education showed statistically significantly lower risks of cancer (0.43 (95% CI: 0.27–0.68) for head and neck, 0.52(0.38–0.69) for stomach, and 0.52(0.38–0.71) for colorectum). Consistent with these results for the educational level, the ADI in quintiles showed positive associations with head and neck, esophageal, and stomach cancers (p-trend: p = 0.035 for head and neck, p = 0.02 for esophagus, and p = 0.013 for stomach). Interestingly, the positive association between ADI and stomach cancer risk disappeared in the additional adjustment for Helicobacter pylori infection and/or atrophic gastritis status. In conclusion, a lower SES was associated with an increased risk of digestive cancers in Japan and should be considered in cancer prevention policies for the target population.An association between socioeconomic status (SES) and cancer risk has been reported, but little is known in Asia. We revealed an association between SES, including education level and areal deprivation index (ADI), and digestive tract cancers in Japan. Lower SES was associated with an increased risk of digestive cancers. For stomach cancer, the positive association with ADI disappeared following an additional adjustment of Helicobacter pylori infection and/or atrophic gastritis status. Cancer prevention policy should consider both individual and regional perspectives by the integration of SES in the target population

Phenol Content, Antioxidant Activity and Fibers Profile of Four Tropical Seagrasses From Indonesia

Extracts of methanol, ethyl acetate, and n-hexane of four species of Indonesian seagrasses were used to determine the total phenol contents and their antioxidant activities. Total phenol contents of each extract was determined by spectrophotometer using Follin-Ciocalteu reagent, and the antioxidant activity was measured using 1,1-diphenyl-2-picrylhydrazyl (DPPH). The profile of fibers of each fresh seagrass was performed according to an enzymatic-gravimetric method. All of methanol extracts contained high number of total phenol, except Syringodium isoetifolium the highest content was found in ethyl acetate extract; so that methanol extracts of Thalassia hemprichii, Cymodocea rotundata, Enhalus acoroides and ethyl acetate extract of Syringodium isoetifolium had the highest activities on scavenging DPPH radical. The phenol content in tropical seagrasses was tending to soluble in polar and semi-polar solvents. There was no significant different on the content of total fibers, with values ranges was from 14.32 g/100 g to 15.39 g/100 g. However, the highest content of soluble fiber was found in Enhalus acoroides (8.93 g/100 g) and significantly differed to others

Mother-to-embryo vitellogenin transport in a viviparous teleost Xenotoca eiseni

魚類がお腹の子供に与える栄養素を解明 --哺乳類が失った遺伝子を利用して胎生機構を獲得--. 京都大学プレスリリース. 2019-10-09.Vitellogenin (Vtg), a yolk nutrient protein that is synthesized in the livers of female animals, and subsequently carried into the ovary, contributes to vitellogenesis in oviparous animals. Thus, Vtg levels are elevated during oogenesis. In contrast, Vtg proteins have been genetically lost in viviparous mammals, thus the yolk protein is not involved in their oogenesis and embryonic development. In this study, we identified Vtg protein in the livers of females during the gestation of the viviparous teleost, Xenotoca eiseni. Although vitellogenesis is arrested during gestation, biochemical assays revealed that Vtg protein was present in ovarian tissues and lumen fluid. The Vtg protein was also detected in the trophotaeniae of the intraovarian embryo. Immunoelectron microscopy revealed that Vtg protein is absorbed into intracellular vesicles in the epithelial cells of the trophotaeniae. Furthermore, extraneous Vtg protein injected into the abdominal cavity of a pregnant female was subsequently detected in the trophotaeniae of the intraovarian embryo. Our data suggest that the yolk protein is one of the matrotrophic factors supplied from the mother to the intraovarian embryo during gestation in X. eiseni

Microenvironmental Geometry Guides Platelet Adhesion and Spreading: A Quantitative Analysis at the Single Cell Level

To activate clot formation and maintain hemostasis, platelets adhere and spread onto sites of vascular injury. Although this process is well-characterized biochemically, how the physical and spatial cues in the microenvironment affect platelet adhesion and spreading remain unclear. In this study, we applied deep UV photolithography and protein micro/nanostamping to quantitatively investigate and characterize the spatial guidance of platelet spreading at the single cell level and with nanoscale resolution. Platelets adhered to and spread only onto micropatterned collagen or fibrinogen surfaces and followed the microenvironmental geometry with high fidelity and with single micron precision. Using micropatterned lines of different widths, we determined that platelets are able to conform to micropatterned stripes as thin as 0.6 µm and adopt a maximum aspect ratio of 19 on those protein patterns. Interestingly, platelets were also able to span and spread over non-patterned regions of up to 5 µm, a length consistent with that of maximally extended filopodia. This process appears to be mediated by platelet filopodia that are sensitive to spatial cues. Finally, we observed that microenvironmental geometry directly affects platelet biology, such as the spatial organization and distribution of the platelet actin cytoskeleton. Our data demonstrate that platelet spreading is a finely-tuned and spatially-guided process in which spatial cues directly influence the biological aspects of how clot formation is regulated

Role of Phagocytosis in the Pro-Inflammatory Response in LDL-Induced Foam Cell Formation; a Transcriptome Analysis

Excessive accumulation of lipid inclusions in the arterial wall cells (foam cell formation) caused by modified low-density lipoprotein (LDL) is the earliest and most noticeable manifestation of atherosclerosis. The mechanisms of foam cell formation are not fully understood and can involve altered lipid uptake, impaired lipid metabolism, or both. Recently, we have identified the top 10 master regulators that were involved in the accumulation of cholesterol in cultured macrophages induced by the incubation with modified LDL. It was found that most of the identified master regulators were related to the regulation of the inflammatory immune response, but not to lipid metabolism. A possible explanation for this unexpected result is a stimulation of the phagocytic activity of macrophages by modified LDL particle associates that have a relatively large size. In the current study, we investigated gene regulation in macrophages using transcriptome analysis to test the hypothesis that the primary event occurring upon the interaction of modified LDL and macrophages is the stimulation of phagocytosis, which subsequently triggers the pro-inflammatory immune response. We identified genes that were up- or downregulated following the exposure of cultured cells to modified LDL or latex beads (inert phagocytosis stimulators). Most of the identified master regulators were involved in the innate immune response, and some of them were encoding major pro-inflammatory proteins. The obtained results indicated that pro-inflammatory response to phagocytosis stimulation precedes the accumulation of intracellular lipids and possibly contributes to the formation of foam cells. In this way, the currently recognized hypothesis that the accumulation of lipids triggers the pro-inflammatory response was not confirmed. Comparative analysis of master regulators revealed similarities in the genetic regulation of the interaction of macrophages with naturally occurring LDL and desialylated LDL. Oxidized and desialylated LDL affected a different spectrum of genes than naturally occurring LDL. These observations suggest that desialylation is the most important modification of LDL occurring in vivo. Thus, modified LDL caused the gene regulation characteristic of the stimulation of phagocytosis. Additionally, the knock-down effect of five master regulators, such as IL15, EIF2AK3, F2RL1, TSPYL2, and ANXA1, on intracellular lipid accumulation was tested. We knocked down these genes in primary macrophages derived from human monocytes. The addition of atherogenic naturally occurring LDL caused a significant accumulation of cholesterol in the control cells. The knock-down of the EIF2AK3 and IL15 genes completely prevented cholesterol accumulation in cultured macrophages. The knock-down of the ANXA1 gene caused a further decrease in cholesterol content in cultured macrophages. At the same time, knock-down of F2RL1 and TSPYL2 did not cause an effect. The results obtained allowed us to explain in which way the inflammatory response and the accumulation of cholesterol are related confirming our hypothesis of atherogenesis development based on the following viewpoints: LDL particles undergo atherogenic modifications that, in turn, accompanied by the formation of self-associates; large LDL associates stimulate phagocytosis; as a result of phagocytosis stimulation, pro-inflammatory molecules are secreted; these molecules cause or at least contribute to the accumulation of intracellular cholesterol. Therefore, it became obvious that the primary event in this sequence is not the accumulation of cholesterol but an inflammatory response

Combination of fluoxetine and extinction treatments forms a unique synaptic protein profile that correlates with long-term fear reduction in adult mice

Peer reviewe

High-Resolution Near-Infrared Polarimetry of a Circumstellar Disk around UX Tau A

We present H-band polarimetric imagery of UX Tau A taken with HiCIAO/AO188 on the Subaru Telescope. UX Tau A has been classified as a pre-transitional disk object, with a gap structure separating its inner and outer disks. Our imagery taken with the 0.15 (21 AU) radius coronagraphic mask has revealed a strongly polarized circumstellar disk surrounding UX Tau A which extends to 120 AU, at a spatial resolution of 0.1 (14 AU). It is inclined by 46 \pm 2 degree as the west side is nearest. Although SED modeling and sub-millimeter imagery suggested the presence of a gap in the disk, with the inner edge of the outer disk estimated to be located at 25 - 30 AU, we detect no evidence of a gap at the limit of our inner working angle (23 AU) at the near-infrared wavelength. We attribute the observed strong polarization (up to 66 %) to light scattering by dust grains in the disk. However, neither polarization models of the circumstellar disk based on Rayleigh scattering nor Mie scattering approximations were consistent with the observed azimuthal profile of the polarization degrees of the disk. Instead, a geometric optics model of the disk with nonspherical grains with the radii of 30 micron meter is consistent with the observed profile. We suggest that the dust grains have experienced frequent collisional coagulations and have grown in the circumstellar disk of UX Tau A.Comment: 20 pages, 8 figures, and 1 table. accepted to PAS

A retrospective case-control study of hepatitis C virus infection and oral lichen planus in Japan: association study with mutations in the core and NS5A region of hepatitis C virus

<p>Abstract</p> <p>Background</p> <p>The aims of this study were to assess the prevalence of hepatitis C virus (HCV) infection in Japanese patients with oral lichen planus and identify the impact of amino acid (aa) substitutions in the HCV core region and IFN-sensitivity-determining region (ISDR) of nonstructural protein 5A (NS5A) associated with lichen planus.</p> <p>Methods</p> <p>In this retrospective study, 59 patients (group 1-A) with oral lichen planus among 226 consecutive patients who visited our hospital and 85 individuals (group 1-B, controls) with normal oral mucosa were investigated for the presence of liver disease and HCV infection. Risk factors for the presence of oral lichen planus were assessed by logistic regression analysis. We compared aa substitutions in the HCV core region (70 and/or 91) and ISDR of NS5A of 12 patients with oral lichen planus (group 2-A) and 7 patients who did not have oral lichen planus (group 2-B) among patients (high viral loads, genotype 1b) who received interferon (IFN) therapy in group1-A.</p> <p>Results</p> <p>The prevalence of anti-HCV and HCV RNA was 67.80% (40/59) and 59.32% (35/59), respectively, in group 1-A and 31.76% (27/85) and 16.47% (14/85), respectively, in group 1-B. The prevalence of anti-HCV (<it>P </it>< 0.0001) and HCV RNA (<it>P </it>< 0.0001) in group 1-A was significantly higher than those in group 1-B. According to multivariate analysis, three factors - positivity for HCV RNA, low albumin level (< 4.0 g/dL), and history of smoking - were associated with the development of oral lichen planus. The adjusted odds ratios for these three factors were 6.58, 3.53 and 2.58, respectively, and each was statistically significant. No significant differences in viral factors, such as aa substitutions in the core region and ISDR of NS5A, were detected between the two groups (groups 2-A and -B).</p> <p>Conclusion</p> <p>We observed a high prevalence of HCV infection in patients with oral lichen planus. Longstanding HCV infection, hypoalbuminemia, and smoking were significant risk factors for the presence of oral lichen planus in patients. It is advisable for Japanese patients with lichen planus to be tested for HCV infection during medical examination.</p