Brain natriuretic peptide suppresses pain induced by BmK I, a sodium channel-specific modulator, in rats.

Background: A previous study found that brain natriuretic peptide (BNP) inhibited inflammatory pain via activating its receptor natriuretic peptide receptor A (NPRA) in nociceptive sensory neurons. A recent study found that functional NPRA is expressed in almost all the trigeminal ganglion (TG) neurons at membrane level suggesting a potentially important role for BNP in migraine pathophysiology. Methods: An inflammatory pain model was produced by subcutaneous injection of BmK I, a sodium channel-specific modulator from venom of Chinese scorpion Buthus martensi Karsch. Quantitative PCR, Western Blot, and immunohistochemistry were used to detect mRNA and protein expression of BNP and NPRA in dorsal root ganglion (DRG) and dorsal horn of spinal cord. Whole-cell patch clamping experiments were conducted to record large-conductance Ca2+-activated K+ (BKCa) currents of membrane excitability of DRG neurons. Spontaneous and evoked pain behaviors were examined. Results: The mRNA and protein expression of BNP and NPRA was up-regulated in DRG and dorsal horn of spinal cord after BmK I injection. The BNP and NPRA was preferentially expressed in small-sized DRG neurons among which BNP was expressed in both CGRP-positive and IB4-positive neurons while NPRA was preferentially expressed in CGRP-positive neurons. BNP increased the open probability of BKCa channels and suppressed the membrane excitability of small-sized DRG neurons. Intrathecal injection of BNP significantly inhibited BmK-induced pain behaviors including both spontaneous and evoked pain behaviors. Conclusions: These results suggested that BNP might play an important role as an endogenous pain reliever in BmK I-induced inflammatory pain condition. It is also suggested that BNP might play a similar role in other pathophysiological pain conditions including migraine

Reinforcement-Learning based Portfolio Management with Augmented Asset Movement Prediction States

Portfolio management (PM) is a fundamental financial planning task that aims to achieve investment goals such as maximal profits or minimal risks. Its decision process involves continuous derivation of valuable information from various data sources and sequential decision optimization, which is a prospective research direction for reinforcement learning (RL). In this paper, we propose SARL, a novel State-Augmented RL framework for PM. Our framework aims to address two unique challenges in financial PM: (1) data heterogeneity -- the collected information for each asset is usually diverse, noisy and imbalanced (e.g., news articles); and (2) environment uncertainty -- the financial market is versatile and non-stationary. To incorporate heterogeneous data and enhance robustness against environment uncertainty, our SARL augments the asset information with their price movement prediction as additional states, where the prediction can be solely based on financial data (e.g., asset prices) or derived from alternative sources such as news. Experiments on two real-world datasets, (i) Bitcoin market and (ii) HighTech stock market with 7-year Reuters news articles, validate the effectiveness of SARL over existing PM approaches, both in terms of accumulated profits and risk-adjusted profits. Moreover, extensive simulations are conducted to demonstrate the importance of our proposed state augmentation, providing new insights and boosting performance significantly over standard RL-based PM method and other baselines.Comment: AAAI 202

Mining the Virgin Land of Neurotoxicology: A Novel Paradigm of Neurotoxic Peptides Action on Glycosylated Voltage-Gated Sodium Channels

Voltage-gated sodium channels (VGSCs) are important membrane protein carrying on the molecular basis for action potentials (AP) in neuronal firings. Even though the structure-function studies were the most pursued spots, the posttranslation modification processes, such as glycosylation, phosphorylation, and alternative splicing associating with channel functions captured less eyesights. The accumulative research suggested an interaction between the sialic acids chains and ion-permeable pores, giving rise to subtle but significant impacts on channel gating. Sodium channel-specific neurotoxic toxins, a family of long-chain polypeptides originated from venomous animals, are found to potentially share the binding sites adjacent to glycosylated region on VGSCs. Thus, an interaction between toxin and glycosylated VGSC might hopefully join the campaign to approach the role of glycosylation in modulating VGSCs-involved neuronal network activity. This paper will cover the state-of-the-art advances of researches on glycosylation-mediated VGSCs function and the possible underlying mechanisms of interactions between toxin and glycosylated VGSCs, which may therefore, fulfill the knowledge in identifying the pharmacological targets and therapeutic values of VGSCs

Impaired dendritic cell maturation and IL-10 production following H. pylori stimulation in gastric cancer patients

The current study was to investigate the interaction between Helicobacter pylori and human dendritic cells (DCs). Whether impaired DC function can influence the outcome of H. pylori infections. Human monocyte-derived DCs (MDDCs) from five gastric cancer patients and nine healthy controls were stimulated with H. pylori. Maturation markers of MDDC were examined by flow cytometry. IL-10 and TNF-α released by MDDCs and IL-17 produced by T cells were measured by ELISA. Regulatory signaling pathways of IL-10 were examined by ELISA, western blotting, and chromatin immunoprecipitation assay. The results showed that as compared with healthy individuals, the maturation marker CD40 in MDDCs, IL-17A expression from T cells, and IL-10 expression from MDDCs were significantly lower in gastric cancer patients. Blocking DC-SIGN, TLR2, and TLR4 could reverse H. pylori-associated IL-10 production. Activation of the p38 MAPK and NF-kB signaling pathways concomitant with decreased tri-methylated H3K9 and increased acetylated H3 accounted for the effect of H. pylori on IL-10 expression. Furthermore, upregulated IL-10 expression was significantly suppressed in H. pylori-pulsed MDDCs by histone acetyltransferase and methyltransferase inhibitors. Taken together, impaired DC function contributes to the less effective innate and adaptive immune responses against H. pylori seen in gastric cancer patients. H. pylori can regulate IL-10 production through Toll-like and DC-SIGN receptors, activates p-p38 MAPK signaling and the transcription factors NF-kB, and modulates histone modification

Exposure to Phthalates and Phenols during Pregnancy and Offspring Size at Birth

Background: Data concerning the effects of prenatal exposures to phthalates and phenols on fetal growth are limited in humans. Previous findings suggest possible effects of some phenols on male birth weight

空間構成と民族芸術からみた福建地方の伝統的商家住宅の特性に関する研究

本調査研究は、明清時代の中国の福建省における商家住宅を対象に、建築の配置構成および吉祥彫刻を中心とした精神文化的要素の配置構成から、住居空間の構成原理を考察することを目的としている。具体的な調査地には、福建地方の民居の多様性を簡便に把握する意図のもと、.北の武夷山市に所在する下梅古民居群と、.南の泉州市及び南安市に所在する古民居をとりあげ、2011年8月と2012年2月の2度にわたり、現地調査を実施した。調査の結果、以下の結論を得た。すなわち、下梅村と泉州・南安とでは、門楼の有無という建築構成上の大きな差異が存在するものの、吉祥彫刻の配置の面から考えると、下梅村の門楼が泉州・南安の下庁（門庁）に相当する役割を果たしていると考えられ、いずれも入口に吉祥彫刻による装飾を高密に集中させる点が共通している。そしてさらに、彫刻の寓意内容においても、一般的な吉祥祈願や品格の表現、さらには個人的な願望に至るまで、同様のモチーフが取り入れられていることがわかった。これらの事実は、両地域が建築形式の相違を超えて、一定の精神文化を共有していることを意味していると考えられる。The main purpose of this research is considering the architectural character of traditional merchant courtyards in Fujian(福建) district, especially from the viewpoint of space constitution and various ethnic carvings which stand for all kinds of auspiciousness. We chose the traditional merchant courtyards as the research fields in Xiamei(下梅), Wuyishan(武夷山) City and in Quanzhou(泉州) City and Nanan(南安) City, and made twice researches in August 2011 and February 2012.Through those researches, we got the following results;In architectural constitution, it is obvious difference between Xiamei and Quanzhou/Nanan whether the storied gate(門楼) exists or not. But in auspicious carvings constitution, both areas seems to have almost the same character because the gate hall(下庁/門庁) in Quanzhou/Nanan plays the same role with the storied gate in Xiamei. And the most of the auspicious carvings are gathered in the storied gate and the gate hall. In addition, those auspicious carvings in both areas resemble each other in the allegorical meanings. This fact means that these areas have common spiritual culture