Activation of hedgehog signaling is not a frequent event in ovarian cancers

The hedgehog (Hh) signaling pathway regulates many processes of development and tissue homeostasis. Activation of hedgehog signaling has been reported in about 30% of human cancer including ovarian cancer. Inhibition of hedgehog signaling has been pursued as an effective strategy for cancer treatment including an ongoing phase II clinical trial in ovarian cancer. However, the rate of hedgehog signaling activation in ovarian cancer was reported differently by different groups. To predict the successful for future clinical trials of hedgehog signaling inhibitors in ovarian cancer, we assessed hedgehog pathway activation in 34 ovarian epithelial tumor specimens through analyses of target gene expression by in-situ hybridization, immunohistochemistry, RT-PCR and real-time PCR. In contrast to previous reports, we only detected a small proportion of ovarian cancers with hedgehog target gene expression, suggesting that identification of the tumors with activated hedgehog signaling activation will facilitate chemotherapy with hedgehog signaling inhibitors

Cortical Source Multivariate EEG Synchronization Analysis on Amnestic Mild Cognitive Impairment in Type 2 Diabetes

Is synchronization altered in amnestic mild cognitive impairment (aMCI) and normal cognitive functions subjects in type 2 diabetes mellitus (T2DM)? Resting eye-closed EEG data were recorded in 8 aMCI subjects and 11 age-matched controls in T2DM. Three multivariate synchronization algorithms (S-estimator (S), synchronization index (SI), and global synchronization index (GSI)) were used to measure the synchronization in five ROIs of sLORETA sources for seven bands. Results showed that aMCI group had lower synchronization values than control groups in parietal delta and beta2 bands, temporal delta and beta2 bands, and occipital theta and beta2 bands significantly. Temporal (r=0.629; P=0.004) and occipital (r=0.648; P=0.003) theta S values were significantly positive correlated with Boston Name Testing. In sum, each of methods reflected that the cortical source synchronization was significantly different between aMCI and control group, and these difference correlated with cognitive functions

Analysis of entropies based on empirical mode decomposition in amnesic mild cognitive impairment of diabetes mellitus

EEG characteristics that correlate with the cognitive functions are important in detecting mild cognitive impairment (MCI) in T2DM. To investigate the complexity between aMCI group and age-matched non-aMCI control group in T2DM, six entropies combining empirical mode decomposition (EMD), including Approximate entropy (ApEn), Sample entropy (SaEn), Fuzzy entropy (FEn), Permutation entropy (PEn), Power spectrum entropy (PsEn) and Wavelet entropy (WEn) were used in the study. A feature extraction technique based on maximization of the area under the curve (AUC) and a support vector machine (SVM) were subsequently used to for features selection and classification. Finally, Pearson's linear correlation was employed to study associations between these entropies and cognitive functions. Compared to other entropies, FEn had a higher classification accuracy, sensitivity and specificity of 68%, 67.1% and 71.9%, respectively. Top 43 salient features achieved classification accuracy, sensitivity and specificity of 73.8%, 72.3% and 77.9%, respectively. P4, T4 and C4 were the highest ranking salient electrodes. Correlation analysis showed that FEn based on EMD was positively correlated to memory at electrodes F7, F8 and P4, and PsEn based on EMD was positively correlated to Montreal cognitive assessment (MoCA) and memory at electrode T4. In sum, FEn based on EMD in right-temporal and occipital regions may be more suitable for early diagnosis of the MCI with T2DM

Data-driven MHD simulation of a sunspot rotating active region leading to solar eruption

Solar eruptions are the leading driver of space weather, and it is vital for space weather forecast to understand in what conditions the solar eruptions can be produced and how they are initiated. The rotation of sunspots around their umbral center has long been considered as an important condition in causing solar eruptions. To unveil the underlying mechanisms, here we carried out a data-driven magnetohydrodynamics simulation for the event of a large sunspot with rotation for days in solar active region NOAA 12158 leading to a major eruption. The photospheric velocity as recovered from the time sequence of vector magnetograms are inputted directly at the bottom boundary of the numerical model as the driving flow. Our simulation successfully follows the long-term quasi-static evolution of the active region until the fast eruption, with magnetic field structure consistent with the observed coronal emission and onset time of simulated eruption matches rather well with the observations. Analysis of the process suggests that through the successive rotation of the sunspot the coronal magnetic field is sheared with a vertical current sheet created progressively, and once fast reconnection sets in at the current sheet, the eruption is instantly triggered, with a highly twisted flux rope originating from the eruption. This data-driven simulation stresses magnetic reconnection as the key mechanism in sunspot rotation leading to eruption.Comment: Accept by A&

The Influence of Self-Relevance and Cultural Values on Moral Orientation

Moral orientation refers to moral values that have a consistent guiding orientation toward an individual's moral cognition and behavior. Gilligan (1982) proposed that individuals have two moral orientations, namely “justice” and “care.” In the current study, we investigated the influence of self-relevance and cultural values on justice and care by using Single Attribute Implicit Association Test (SA-IAT). In Experiments 1 and 2, we adopted cultural icon prime paradigm to examine the effects of different self-referential stimuli (self, friend, and stranger) on implicit moral justice and care orientation under two cultural value conditions: traditionality, modernity, and neutral cultural values. Participants exhibited more difference toward different self-referential stimuli in the traditionality condition than in the modernity condition; the priming of traditional culture aggravated the differential order, whereas the priming of modernity weakened the differential order regarding implicitly just moral orientation. In the implicit care orientation, participants in the modern culture group exhibited the least difference to different self-referential stimuli compared with the other two groups, and the traditional group and the control group did not differ significantly. These findings indicate that psychological modernity weakens the degree of self-related effect in implicit justice and care orientation, whereas traditional culture aggravates the differential order in justice orientation. The current studies provide empirical support for theories relating moral orientation, also informing the literature on the role of self-relevance information and cultural values in moral decision making

Strigolactone alleviates the salinity-alkalinity stress of Malus hupehensis seedlings

Salinity-alkalinity stress can remarkably affect the growth and yield of apple. Strigolactone (SL) is a class of carotenoid-derived compounds that functions in stress tolerance. However, the effects and mechanism of exogenous SL on the salinity-alkalinity tolerance of apple seedlings remain unclear. Here, we assessed the effect of SL on the salinity-alkalinity stress response of Malus hupehensis seedlings. Results showed that treatment with 100 μM exogenous SL analog (GR24) could effectively alleviate salinity-alkalinity stress with higher chlorophyll content and photosynthetic rate than the apple seedlings without GR24 treatment. The mechanism was also explored: First, exogenous GR24 regulated the expression of Na+/K+ transporter genes and decreased the ratio of Na+/K+ in the cytoplasm to maintain ion homeostasis. Second, exogenous GR24 increased the enzyme activities of superoxide, peroxidase and catalase, thereby eliminating reactive oxygen species production. Third, exogenous GR24 alleviated the high pH stress by regulating the expression of H+-ATPase genes and inducing the production of organic acid. Last, exogenous GR24 application increased endogenous acetic acid, abscisic acid, zeatin riboside, and GA3 contents for co-responding to salinity-alkalinity stress indirectly. This study will provide important theoretical basis for analyzing the mechanism of exogenous GR24 in improving salinity-alkalinity tolerance of apple

The <i>Sinocyclocheilus</i> cavefish genome provides insights into cave adaptation

BACKGROUND: An emerging cavefish model, the cyprinid genus Sinocyclocheilus, is endemic to the massive southwestern karst area adjacent to the Qinghai-Tibetan Plateau of China. In order to understand whether orogeny influenced the evolution of these species, and how genomes change under isolation, especially in subterranean habitats, we performed whole-genome sequencing and comparative analyses of three species in this genus, S. grahami, S. rhinocerous and S. anshuiensis. These species are surface-dwelling, semi-cave-dwelling and cave-restricted, respectively. RESULTS: The assembled genome sizes of S. grahami, S. rhinocerous and S. anshuiensis are 1.75 Gb, 1.73 Gb and 1.68 Gb, respectively. Divergence time and population history analyses of these species reveal that their speciation and population dynamics are correlated with the different stages of uplifting of the Qinghai-Tibetan Plateau. We carried out comparative analyses of these genomes and found that many genetic changes, such as gene loss (e.g. opsin genes), pseudogenes (e.g. crystallin genes), mutations (e.g. melanogenesis-related genes), deletions (e.g. scale-related genes) and down-regulation (e.g. circadian rhythm pathway genes), are possibly associated with the regressive features (such as eye degeneration, albinism, rudimentary scales and lack of circadian rhythms), and that some gene expansion (e.g. taste-related transcription factor gene) may point to the constructive features (such as enhanced taste buds) which evolved in these cave fishes. CONCLUSION: As the first report on cavefish genomes among distinct species in Sinocyclocheilus, our work provides not only insights into genetic mechanisms of cave adaptation, but also represents a fundamental resource for a better understanding of cavefish biology. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12915-015-0223-4) contains supplementary material, which is available to authorized users

Proteomics and Phosphoproteomics of Heat Stress-Responsive Mechanisms in Spinach

Elevated temperatures limit plant growth and reproduction and pose a growing threat to agriculture. Plant heat stress response is highly conserved and fine-tuned in multiple pathways. Spinach (Spinacia oleracea L.) is a cold tolerant but heat sensitive green leafy vegetable. In this study, heat adaptation mechanisms in a spinach sibling inbred heat-tolerant line Sp75 were investigated using physiological, proteomic, and phosphoproteomic approaches. The abundance patterns of 911 heat stress-responsive proteins, and phosphorylation level changes of 45 phosphoproteins indicated heat-induced calcium-mediated signaling, ROS homeostasis, endomembrane trafficking, and cross-membrane transport pathways, as well as more than 15 transcription regulation factors. Although photosynthesis was inhibited, diverse primary and secondary metabolic pathways were employed for defense against heat stress, such as glycolysis, pentose phosphate pathway, amino acid metabolism, fatty acid metabolism, nucleotide metabolism, vitamin metabolism, and isoprenoid biosynthesis. These data constitute a heat stress-responsive metabolic atlas in spinach, which will springboard further investigations into the sophisticated molecular mechanisms of plant heat adaptation and inform spinach molecular breeding initiatives

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead