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Avian influenza virus A/chicken/Jiangsu/1001/2013(H5N2) was identified from a healthy chicken in an eastern China poultry market. Whole-genome analysis demonstrated that the H5N2 virus originated from a reassortance between a previous A/chicken/Hebei/1102/2010(H5N2) virus and an endemic H5N1 virus. The results indicated that continuing reassortance of H5N2 has been occurring in domestic poultry of China.

Engaging in novel/exciting ("self-expanding") activities activates the mesolimbic dopamine pathway, a brain reward pathway also associated with the rewarding effects of nicotine. This suggests that self-expanding activities can potentially substitute for the reward from nicotine. We tested this model among nicotine-deprived smokers who, during fMRI scanning, played a series of two-player cooperative games with a relationship partner. Games were randomized in a 2 (self-expanding vs. not) x 2 (cigarette cue present vs. absent) design. Self-expansion conditions yielded significantly greater activation in a reward region (caudate) than did non-self-expansion conditions. Moreover, when exposed to smoking cues during the self-expanding versus the non-self-expanding cooperative games, smokers showed less activation in a cigarette cue-reactivity region, a priori defined [temporo-parietal junction (TPJ)] from a recent meta-analysis of cue-reactivity. In smoking cue conditions, increases in excitement associated with the self-expanding condition (versus the non-self-expanding condition) were also negatively correlated with TPJ activation. These results support the idea that a self-expanding activity promoting reward activation attenuates cigarette cue-reactivity among nicotine-deprived smokers. Future research could focus on the parameters of self-expanding activities that produce this effect, as well as test the utility of self-expansion in clinical interventions for smoking cessation.

The present experiments were carried out to investigate the possible direct effects of estrogens (E) on the growth of colon cancer cells. Estradiol exhibited a concentration-dependent biphasic growth effect on a mouse colon cancer cell line (MC-26). Low concentrations of estradiol (10−10 m to 10−8 m) had a growth-stimulatory effect, while higher concentrations (10−7 m to 10−6 m) were growth-inhibitory. Estrogen receptor (ER) mRNA as well as specific, saturable binding of estradiol to ER (Kd=0.3nm, Bmax=0.72 fmol/μg DNA) was identified in these cells. In addition to the classical high affinity ER, lower affinity, higher capacity estrogen binding sites (Kd=35mm, Bmax=30 fmol/μg DNA) were also characterized in MC-26 cells. These two types of estrogen binding sites exhibited distinct binding specificities for E and antiestrogens. Treatment of MC-26 cells with an oligodeoxy-nucleotide antisense to the translation start codon of ER mRNA did not alter the grown-inhibitory effect of 10−6 m estradiol, demonstrating that the growth-inhibitory effect of high concentrations of E was not mediated by ER; we have previously shown that under the same conditions, ER antisense oligonucleotides do block the growth-stimulatory effects of 10−9 m E2 in MC-26 cells. The data suggest that physiological concentrations of estradiol acting via the classical ER may have a proliferative effect on the growth of colon cancer cells. However, in situations where there are high luminal concentrations of estrogenic compounds, they may act on low affinity estrogen binding sites that mediate the growth-inhibitory effect.

We sought to explore the treatment effects and the repair mechanisms of bone marrow derived mesenchymal stem cells (MSCs) during HCl-induced acute lung injury (ALI). MSCs were delivered through the tail veins of rats 24 h after intranasal instillation of HCl. The results showed that MSCs did not ameliorate the histopathologic changes of ALI and pulmonary fibrosis. We found that the activated Wnt/β-catenin signaling may regulate the differentiation of MSCs and is associated with lung fibroblasts activation, pulmonary fibrosis and tissue repair process in ALI rats. Immunofluorescence and histology analysis indicated that activated canonical Wnt/β-catenin signaling induced most MSCs to differentiate into myofibroblasts or fibroblasts in vivo. However, inhibition of Wnt/β-catenin signaling by Dickkopf-1 (DKK1) promotes epithelial differentiation of MSCs induced by native alveolar epithelial cells which are beneficial to repair the injured lung epithelium. Inhibition of Wnt/β-catenin signaling after MSCs transplantation ameliorated pulmonary fibrosis and improved pulmonary function which attenuated the lung injury. In vitro study, activation of the Wnt/β-catenin signaling stimulated MSCs to express myofibroblasts markers, which was attenuated by DKK1. Furthermore, Wnt3α activated Wnt/β-catenin signaling in lung fibroblasts to enhance the expression of collagen I, vimentin and α-smooth muscle actin, but DKK1 attenuated these proteins expression. These findings demonstrated that canonical Wnt/β-catenin signaling plays a key role in regulating differentiation of MSCs in vivo or in vitro and the pathogenesis of fibrotic diseases. Our study suggested that inhibition of abnormal activated Wnt/β-catenin signaling would promote MSCs epithelial differentiation to repair lung injury and reduce pulmonary fibrosis.

Controversies and risks continue to be reported about exogenous mesenchymal stem cell-based therapies. In contrast with employing exogenous stem cells, making use of lung resident mesenchymal stem cells (LR-MSCs) could be advantageous. Our study sought to isolate the LR-MSCs and explore their potential to differentiate into alveolar epithelial type II cells (ATII cells). Total lung cells were first precultured, from which the Sca-1(+) CD45(-) CD31(-) population was purified using fluorescence activated cell sorting (FACS). By these methods, it would seem that the Sca-1(+) CD45(-) CD31(-) cells were LR-MSCs. Similar to bone marrow derived mesenchymal stem cells (BM-MSCs), these cells express Sca-1, CD29, CD90, CD44 and CD106, but not CD31 or CD45. They share the same gene expression file with the BM-MSCs and have a similar DNA content during long-term culturing. Furthermore, they could be serially passaged with all these properties being sustained. Above all, LR-MSCs could differentiate into ATII cells when co-cultured with ATII cells in a trans-well system. These findings demonstrated that the Sca-1(+) CD45(-) CD31(-) cells appear to be LR-MSCs that can differentiate into ATII cells. This approach may hold promise for their use in the treatment of lung disease.

In this paper, we show that the Jacobiator $J$ of a pre-Courant algebroid is closed naturally. The corresponding equivalence class $[J^\flat]$ is defined as the Pontryagin class, which is the obstruction of a pre-Courant algebroid to be deformed into a Courant algebroid. We construct a Leibniz 2-algebra and a Lie 2-algebra associated to a pre-Courant algebroid and prove that these algebraic structures are isomorphic under deformations. Finally, we introduce the twisted action of a Lie algebra on a manifold to give more examples of pre-Courant algebroids, which include the Cartan geometry., 26 pages

Early-stage romantic love is associated with activation in reward and motivation systems of the brain. Can these localized activations, or others, predict long-term relationship stability? We contacted participants from a previous fMRI study of early-stage love by Xu et al. [34] after 40 months from initial assessments. We compared brain activation during the initial assessment at early-stage love for those who were still together at 40 months and those who were apart, and surveyed those still together about their relationship happiness and commitment at 40 months. Six participants who were still with their partners at 40 months (compared to six who had broken up) showed less activation during early-stage love in the medial orbitofrontal cortex, right subcallosal cingulate and right accumbens, regions implicated in long-term love and relationship satisfaction [1,2]. These regions of deactivation at the early stage of love were also negatively correlated with relationship happiness scores collected at 40 months. Other areas involved were the caudate tail, and temporal and parietal lobes. These data are preliminary evidence that neural responses in the early stages of romantic love can predict relationship stability and quality up to 40 months later in the relationship. The brain regions involved suggest that forebrain reward functions may be predictive for relationship stability, as well as regions involved in social evaluation, emotional regulation, and mood.

RNA polymerase II initiates from low complexity sequences so cells must reliably distinguish “real” from “cryptic” promoters and maintain fidelity to the former. Further, this must be performed under a range of conditions, including those found within inactive and highly transcribed regions. Here, we used genome-scale screening to identify those factors that regulate the use of a specific cryptic promoter and how this is influenced by the degree of transcription over the element. We show that promoter fidelity is most reliant on histone gene transactivators (Spt10, Spt21) and H3-H4 chaperones (Asf1, HIR complex) from the replication-independent deposition pathway. Mutations of Rtt106 that abrogate its interactions with H3-H4 or dsDNA permit extensive cryptic transcription comparable with replication-independent deposition factor deletions. We propose that nucleosome shielding is the primary means to maintain promoter fidelity, and histone replacement is most efficiently mediated in yeast cells by a HIR/Asf1/H3-H4/Rtt106 pathway.

Mesenchymal stem cells (MSCs) can promote tumor growth in a mouse xenograft model, but the exact mechanism remains unclear. In this study, we investigated the effects of bone marrow MSC-derived exosomes (MSC-exosomes) on tumor growth in vitro and in vivo. Our results showed that MSC-exosomes promoted tumor growth in vivo. MSC-exosomes enhanced vascular endothelial growth factor (VEGF) expression in tumor cells by activating extracellular signal-regulated kinase1/2 (ERK1/2) pathway. Inhibition of ERK1/2 activation reserved the increase of VEGF level by MSC-exosomes. Our findings demonstrate a new mechanism through which MSC-exosome-mediated cell-cell interactions may contribute to tumor progression.

Early‐stage romantic love has been studied previously in the United States and United Kingdom (Aron et al. [2005]: J Neurophysiol 94:327–337; Bartels and Zeki [2000]: Neuroreport 11:3829–3834; Ortigue et al. [2007]: J Cogn Neurosci 19:1218–1230), revealing activation in the reward and motivation systems of the brain. In this study, we asked what systems are activated for early‐stage romantic love in Easterners, specifically Chinese participants? Are these activations affected by individual differences within a cultural context of Traditionality and Modernity? Also, are these brain activations correlated with later satisfaction in the relationship? In Beijing, we used the same procedure used by Aron et al. (Aron et al. [2005]: J Neurophysiol 94:327–337). The stimuli for 18 Chinese participants were a picture of the face of their beloved, the face of a familiar acquaintance, and a countback task. We found significant activations specific to the beloved in the reward and motivation systems, particularly, the ventral tegmental area and the caudate. The mid‐orbitofrontal cortex and cerebellum were also activated, whereas amygdala, medial orbitofrontal, and medial accumbens activity were decreased relative to the familiar acquaintance. Self‐reported Traditionality and Modernity scores were each positively correlated with activity in the nucleus accumbens, although in different regions and sides of the brain. Activity in the subgenual area and the superior frontal gyrus was associated with higher relationship happiness at 18‐month follow‐up. Our results show that midbrain dopamine‐rich reward/motivation systems were activated by early‐stage romantic love in Chinese participants, as found by other studies. Neural activity was associated with Traditionality and Modernity attitudes as well as with later relationship happiness for Chinese participants. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.

Mesenchymal stem cell (MSC)-like cells, a subpopulation of tumor microenvironment, have been isolated from several tumor tissues. In our previous study, we identified MSC-like cells in human gastric cancer tissues and found their characteristics to be similar to those of bone marrow MSCs. However, whether there are MSC-like cells in adjacent non-cancerous tissues and any difference between the MSC-like cells derived from tumor and non-cancerous tissues are not clear. The aim of this study is to study and research the differences of two mesenchymal stem-like cells. We demonstrate that MSC-like cells can be isolated from both human gastric tumor (hGC-MSCs) and adjacent non-cancerous tissues (hGCN-MSCs) of the same patient. We further compared the characteristics between hGC-MSCs and hGCN-MSCs. Our results revealed that hGC-MSCs and hGCN-MSCs possessed similar morphological properties; stem cell-associated gene expression, as well as multipotential differentiation capability. We also found differences in cell surface markers, pluripotency, and proliferation-related gene expression between hGCN-MSCs and hGC-MSCs. Our findings suggest that MSC-like cells are components of the tumor microenvironment and provide proof for the origin of carcinoma-associated fibroblast, therefore may potentially be used as a target for gastric cancer diagnosis and therapy.

This exploratory study examined the extent to which individual differences in sensory processing sensitivity (SPS), a temperament/personality trait characterized by social, emotional and physical sensitivity, are associated with neural response in visual areas in response to subtle changes in visual scenes. Sixteen participants completed the Highly Sensitive Person questionnaire, a standard measure of SPS. Subsequently, they were tested on a change detection task while undergoing functional magnetic resonance imaging (fMRI). SPS was associated with significantly greater activation in brain areas involved in high-order visual processing (i.e. right claustrum, left occipitotemporal, bilateral temporal and medial and posterior parietal regions) as well as in the right cerebellum, when detecting minor (vs major) changes in stimuli. These findings remained strong and significant after controlling for neuroticism and introversion, traits that are often correlated with SPS. These results provide the first evidence of neural differences associated with SPS, the first direct support for the sensory aspect of this trait that has been studied primarily for its social and affective implications, and preliminary evidence for heightened sensory processing in individuals high in SPS.

The amyloid beta-peptide deposit found in the brain tissue of patients with Alzheimer disease is derived from a large heparin-binding protein precursor APP. The biological function of APP and its homologs is not precisely known. Here we report the x-ray structure of the E2 domain of APL-1, an APP homolog in Caenorhabditis elegans, and compare it to the human APP structure. We also describe the structure of APL-1 E2 in complex with sucrose octasulfate, a highly negatively charged disaccharide, which reveals an unexpected binding pocket between the two halves of E2. Based on the crystal structure, we are able to map, using site-directed mutagenesis, a surface groove on E2 to which heparin may bind. Our biochemical data also indicate that the affinity of E2 for heparin is influenced by pH: at pH 5, the binding appears to be much stronger than that at neutral pH. This property is likely caused by histidine residues in the vicinity of the mapped heparin binding site and could be important for the proposed adhesive function of APL-1.

Helping smokers quit is important as smoking is the number one preventable cause of death in the U.S. Smoking activates the mesolimbic dopamine reward system which is also responsible for pleasure associated with other behaviors, including engaging in novel, exciting and/or challenging (i.e., self-expanding) events. We hypothesized that the reward activation achieved by experiencing self-expanding events can supplant the reinforcement normally provided by smoking and can thus facilitate quitting. We investigated this hypothesis among 74 current and 66 former smokers who reported the self-expanding events they experienced for the 2 months prior to their most successful or final, quit attempt, respectively. Former smokers, compared to current smokers, reported significantly more self-expanding events and that the events were more helpful to their quitting. For current smokers, there was a significant moderate-to-large positive correlation between number of self-expanding events and number of days subsequently abstained from smoking. The results support the proposition that experiencing self-expanding activities or events can be beneficial for smoking abstinence.

Oral lichen planus (OLP), one of the most common oral mucosa diseases, is an auto-immune disease characterized histologically by basal keratinocyte damage and interface lymphocyte reaction. Previous studies have proved ethanol consumption can suppress immune system in many aspects, including inhibiting lymphocytes proliferation and their function, modifying antigen-presentation, etc. Pathogenesis of the OLP mainly comprises of antigen-presentation, lymphocytes activation and keratinocyte apoptosis, all of which may be inhibited by ethanol consumption. Thus, we put forth our hypothesis that chronic ethanol consumption may decrease OLP incidence and OLP treatment except the erosive type may benefit from ethanol consumption. In the discussion, we also talk about the extent of ethanol consumption. Still ethanol abuse is not commended, for it may increase incidence of many other diseases, and moderate ethanol consumption may be potentially beneficial for other auto-immune diseases.

Mesenchymal stem cells (MSCs) have been identified in and isolated from numerous human tissues. The characteristics of mesenchymal stem cells, including their plasticity, the secretion of cytokines, and their low immunogenicity, contribute to their therapeutic potential. It has recently been reported that MSCs are also involved in tumorigenesis and its prognosis. Here, we present the first report of MSC-like cells isolated from human gastric cancer tissues. In our study, gastric cancer-derived MSC-like cells (hGC-MSCs) were isolated from 13 out of 20 cancer tissue samples. Their characteristics, including their morphology, surface antigens, specific gene expression, and differentiation potential, were similar to those of MSCs derived from human bone marrow (hBM-MSCs) but different from gastric cancer cells. The existence of MSC-like cells in gastric cancer tissues suggests that they may be potential targets for cancer therapy and provides an experimental foundation for investigating their role in the initiation and progression of gastric cancers.

A video content generation support system, based on an interactive approach that maps low-level features to high-level concepts, is proposed. By consulting an ontological semantic object model database, the same semantic objects such as characters, backgrounds, and the main subjects in key frames of each video shots can be queried and automatically annotated based on the similarity of low-level features such as the color, area, and position of each region. Since image recognition techniques are limited in their ability to fully identify and compare images, an additional function is proposed, which uses a coarse model to recover a higher number of similar key frames to provide more relevant results. The content provider can then select relevant key frames interactively from the results to annotate matched objects in them according to the descriptions that are added into the model. Therefore, more complex content can be generated with a higher accuracy by using a combination of the application-oriented operations. The system has high potential for use in object-based interactive multimedia applications. One prototype application is also presented.

Consistent boundary conditions for Alexandrov-Kontsevich-Schwartz-Zaboronsky (AKSZ) sigma models and the corresponding boundary theories are analyzed. As their mathematical structures, we introduce a generalization of differential graded symplectic manifolds, called twisted QP manifolds, in terms of graded symplectic geometry, canonical functions, and QP pairs. We generalize the AKSZ construction of topological sigma models to sigma models with Wess-Zumino terms and show that all the twisted Poisson-like structures known in the literature can actually be naturally realized as boundary conditions for AKSZ sigma models.

Self-expanding experiences like falling in love or engaging in novel, exciting and interesting activities activate the same brain reward mechanism (mesolimbic dopamine pathway) that reinforces drug use and abuse, including tobacco smoking. This suggests the possibility that reward from smoking is substitutable by self-expansion (through competition with the same neural system), potentially aiding cessation efforts. Using a model of self-expansion in the context of romantic love, the present fMRI experiment examined whether, among nicotine-deprived smokers, relationship self-expansion is associated with deactivation of cigarette cue-reactivity regions. Results indicated that among participants who were experiencing moderate levels of craving, cigarette cue-reactivity regions (e.g., cuneus and posterior cingulate cortex) showed significantly less activation during self-expansion conditions compared with control conditions. These results provide evidence that rewards from one domain (self-expansion) can act as a substitute for reward from another domain (nicotine) to attenuate cigarette cue reactivity.

In vivo and epidemiological data suggest a mitogenic role for estrogens (E) in colon cancer. The presence of estrogen receptor (ER) and ER mRNA in colonic epithelium and colon cancer cells, make it necessary to explore the possible direct effects of E on colon cancer growth. In this study, a 15-mer oligodoxynucleotide (oligo) antisense to the region of the translation start codon of estrogen receptor mRNA inhibited ER expression in a mouse colon cancer cell line (MC-26), as determined by receptor binding assay. Antisense oligo also decreased ER mRNA levels in MC-26 cells. The growth-stimulatory effect of E was abolished by antisense oligo treatment, demonstrating that the ER is directly involved in the regulation of colon cancer cell growth.

Reproductive and maturational nutritive needs are examples of situations in which alterations in circulating concentrations of estrogens are associated with changes in intestinal epithelial function. However, it is not clear that any of these effects is due to direct interaction of estrogen with intestinal epithelial estrogen receptors (ER). The experiments reported here were designed to determine whether the small intestinal epithelium contains functional ER and might, therefore, be an estrogen-responsive tissue. IEC-6 cells, a non-transformed line of cells isolated from rat small intestinal crypts, were used for many of the experiments, because they provide a pure preparation of crypt epithelial cells. IEC-6 cells were found to exhibit specific saturable binding of estradiol with a Kd of 5 x 10(-10) M and approximately 100 binding sites/cell. Reverse transcriptase-polymerase chain reaction demonstrated that IEC-6 cells as well as epithelial cells from each segment of the rat intestine (duodenum, jejunum, ileum, and colon) contained ER mRNA of the sequence determined from rat uterus. Estradiol was shown to stimulate IEC-6 cell c-fos mRNA content rapidly and transiently in a manner analogous to that which has been previously demonstrated for other estrogen-responsive tissues. These data demonstrate that intestinal epithelial cells contain ER capable of regulating gene transcription and provide the basis for future studies designed to elucidate the role of estrogens in the regulation of intestinal epithelial function and pathophysiology.

Purpose Urinary extracellular vesicles (uEVs) are a novel source of biomarkers. However, urinary Tamm-Horsfall Protein (THP; uromodulin) interferes with all vesicle isolation attempts, precipitates with normal urinary proteins, thus, representing an unwanted "contaminant" in urinary assays. Thus, the aim is to develop a simple method to manage THP efficiently. Experimental design The uEVs are isolated by hydrostatic filtration dialysis (HFD) and treated with a defined solution of urea to optimize release of uEVs from sample. Presence of uEVs is confirmed by transmission electron microscopy, Western blotting, and proteomic profiling in MS. Results Using HFD with urea treatment for uEV isolation reduces sample complexity to a great extent. The novel simplified uEV isolation protocol allows comprehensive vesicle proteomics analysis and should be part of any urine analytics to release all sample constituents from THP trap. Conclusions and clinical relevance The method brings a quick and easy protocol for THP management during uEV isolation, providing major benefits for comprehensive sample analytics.