n Li

Stabilizing parallel G-quadruplex DNA by a new class of ligands: Two non-planar alkaloids through interaction in lateral grooves

Human DNA sequences consisting of tandem guanine (G) nucleotides can fold into a four-stranded structure named G-quadruplex via Hoogsteen hydrogen bonding. As the sequences forming G-quadruplex exist in essential regions of eukaryotic chromosomes and are involved in many important biological processes, the study of their biological functions has currently become a hotspot. Compounds selectively binding and stabilizing G-quadruplex structures have the potential to inhibit telomerase activity or alter oncogene expression levels and thus may act as antitumor agents. Most of reported G-quadruplex ligands generally have planar structures which stabilize G-quadruplex by pi-pi stacking. However, based on a pharmacophore-based virtual screening two non-planar G-quadruplex ligands were found. These two ligands exhibit good capability for G-quadruplex stabilization and prefer binding to paralleled G-quadruplex rather than to duplex DNA. The binding of these ligands to G-quadruplex may result from groove binding at a 2:1 stoichiometry. These results have shown that planar structures are not essential for G-quadruplex stabilizers, which may represent a new class of G-quadruplex-targeted agents as potential antitumor drugs.

The human brain response to acupuncture on same-meridian acupoints: evidence from an fMRI study.

OBJECTIVESnStimulation of acupuncture points (acupoints) located on meridians has been proven to activate specific areas of the human brain, as evidenced by functional imaging studies. To date, the specificity of acupoints located on different meridians has been investigated with functional magnetic resonance image (fMRI). The present fMRI study explored the effects of stimulating 4 acupoints on 2 different meridians for the purpose of researching the characteristic response of acupoints on the same meridian.nnnMATERIALS AND METHODSnThe acupoints studied were LR3 (Taichong) and LR6 (Zhongdu), which belong to the Liver meridian of Foot-Jueyin; ST36 (Zusanli) and ST43 (Xiangu), which belong to the Stomach meridian of Foot-Yangming; and 2 nearby sham acupoints. Fifty-three (53) healthy right-handed subjects were divided randomly into 6 groups. Each group only received acupuncture at one acupoint. All the acupoints in this study were stimulated only on the right side of the subjects body. Through analysis of fMRI data from all subjects, we obtained the activation patterns in the central nervous system (CNS) evoked by acupuncture.nnnRESULTSnIn contrast to the CNS activation by sham acupoint, the results showed that all 4 real acupoints under consideration had the common effect of activating 2 specific areas of the brain: the bilateral primary somatosensory area and the ipsilateral cerebellum. Acupuncture stimulation of both acupoints LR3 and LR6 evoked activation at the ipsilateral superior parietal lobe (BA7). Acupuncture stimulation of both acupoints ST36 and ST43 evoked activation at the ipsilateral middle frontal gyrus (BA10).nnnCONCLUSIONSnThese results suggest that different acupoints on the same meridian may activate certain similar areas of the brain. In addition, acupoints that are commonly used in clinical practice might modulate a greater extent of cortical areas than uncommonly used acupoints.

Screening Potential Antitumor Agents from Natural Plant Extracts by G-Quadruplex Recognition and NMR Methods

mainlyfocusonscreeningmolecule(s)withknownstructure.However,uptonow,thescreeningofG-quadruplexligands from natural plant extracts, a complicated mixturesystem with multiform unknown chemical frames, has notbeenreported.Herein,weaddressanovelapproachforfastscreeningofG-quadruplex ligands from natural plant extracts. Thisapproach includes the following three steps: judging theexistence of G-quadruplex ligand(s) in the test extracts by

Predicting Active Users' Personality Based on Micro-Blogging Behaviors

Because of its richness and availability, micro-blogging has become an ideal platform for conducting psychological research. In this paper, we proposed to predict active users personality traits through micro-blogging behaviors. 547 Chinese active users of micro-blogging participated in this study. Their personality traits were measured by the Big Five Inventory, and digital records of micro-blogging behaviors were collected via web crawlers. After extracting 845 micro-blogging behavioral features, we first trained classification models utilizing Support Vector Machine (SVM), differentiating participants with high and low scores on each dimension of the Big Five Inventory. The classification accuracy ranged from 84% to 92%. We also built regression models utilizing PaceRegression methods, predicting participants scores on each dimension of the Big Five Inventory. The Pearson correlation coefficients between predicted scores and actual scores ranged from 0.48 to 0.54. Results indicated that active users personality traits could be predicted by micro-blogging behaviors.

Verification of Intramolecular Hybrid/Parallel G-Quadruplex Structure under Physiological Conditions Using Novel Cyanine Dye H-Aggregates: Both in Solution and on Au Film

The H-aggregates of a novel cyanine dye, 3,3-di(3-sulfopropyl)-4,5,4,5-dibenzo-9-methyl-thiacarbocyanine triethylammonium salt (MTC), have been fabricated to verify hybrid/parallel intramolecular G-quadruplexes from linear duplex and single-strand DNAs under physiological conditions. The recognition is found to be successful both in solution and on Au film. These results have shown MTC H-aggregates, as a supramolecular system, may be used as a potential excellent probe for DNA structure, both in vitro and in vivo.

A stabilizing and denaturing dual-effect for natural polyamines interacting with G-quadruplexes depending on concentration

Both G-quadruplexes and natural polyamines are intimately associated with tumor growth and proliferation. The effect of the natural polyamines on telomeric and some oncogenic G-quadruplexes including bcl-2, c-kit, and c-myc G-quadruplexes has been studied by using absorption, fluorescence, CD, and NMR methods. The results exhibited an interesting dual-effect depending on polyamineś concentration. Polyamines promote and stabilize G-quadruplexes under a lower concentration (less than 1mM) but denature G-quadruplexes under a higher concentration (more than 1mM). Probably the electrostatic and hydrophobic effect of polyamines and the hydrogen-bonding interaction between guanines and polyamines were respectively responsible for the stabilizing and denaturing effect.

Mass Spectrometry Methodology in Lipid Analysis

Lipidomics is an emerging field, where the structures, functions and dynamic changes of lipids in cells, tissues or body fluids are investigated. Due to the vital roles of lipids in human physiological and pathological processes, lipidomics is attracting more and more attentions. However, because of the diversity and complexity of lipids, lipid analysis is still full of challenges. The recent development of methods for lipid extraction and analysis and the combination with bioinformatics technology greatly push forward the study of lipidomics. Among them, mass spectrometry (MS) is the most important technology for lipid analysis. In this review, the methodology based on MS for lipid analysis was introduced. It is believed that along with the rapid development of MS and its further applications to lipid analysis, more functional lipids will be identified as biomarkers and therapeutic targets and for the study of the mechanisms of disease.

Improving user profile with personality traits predicted from social media content

Existing studies indicate that there exists strong correlation between personality and personal preference, thus personality could potentially be used to build more personalized recommender system. Personality traits are mainly measured by psychological questionnaires, and it is hard to obtain personality traits of large amount of users in real-world scenes.In this paper, we propose a new approach to automatically identify personality traits with Social Media contents in Chinese language environments. Social Media content features were extracted from 1766 Sina micro blog users, and the predicting model is trained with machine learning algorithms.The experimental results demonstrate that users personality traits could be predicted from Social Media contents with acceptable Pearson Correlation, which makes it possible to develop user profiles for recommender system. In future, user profiles with predicted personality traits would be used to enhance the performance of existing personalized recommendation systems.

Ultra-high-performance liquid chromatography electrospray ionization tandem mass spectrometry for accurate analysis of glycerophospholipids and sphingolipids in drug resistance tumor cells

Glycerophospholipids and sphingolipids are important signaling molecules which are involved in many physiological and pathological processes. Here we reported an effective method for accurate analysis of these lipids by liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). The methanol method was adopted for extraction of lipids due to its simplicity and high efficiency. It was found that two subclasses of sphingolipids, sulfatide (ST) and cerebroside (CB), were heat labile, so a decreased temperature in the ion source of MS might be necessary for these compounds analysis. In addition, it was found that the isobaric interferences were commonly existent, for example, the m/z of 16:0/18:1 PC containing two (13)C isotope being identical to that of 16:0/18:0 PC determined by a unit mass resolution mass spectrometer; therefore, a baseline separation of interferential species was required to maintain selectivity and accuracy of analysis. In this work, an ultra-high-performance liquid chromatography (UHPLC)-based method was developed for separation of interferential species. Moreover, in order to deal with the characteristics of different polarity and wide dynamic range of glycerophospholipids and sphingolipids in biological systems, three detecting conditions were combined together for comprehensive and rational analysis of glycerophospholipids and sphingolipids. The method was utilized to profile glycerophospholipids and sphingolipids in drug resistant tumor cells. Our results showed that many lipids were significantly changed in drug resistant tumor cells compared to paired drug sensitive tumor cells. This is a systematic report about the isobaric interferences and heat labile compounds interferences when analyzing glycerophospholipids and sphingolipids by ESI-MS/MS, which aids in ruling out one potential source of systematic error to ensure the accuracy of analysis.

High resolution mass spectrometry coupled with multivariate data analysis revealing plasma lipidomic alteration in ovarian cancer in Asian women.

Ovarian cancer (OC) is the most common cause of death from gynecologic malignancies in women. The identification of reliable diagnostic biomarkers for the early detection of this deadly disease is critical for reducing the mortality rate of OC. Plasma lysophosphatidic acid (LPA) levels were increased from OC patients vs. healthy controls. Therefore, lipidomics may represent an excellent developing prospect for the discovery of diagnostic biomarkers of OC. In this study, a nontargeted lipidomics approach based on ultra performance liquid chromatography-electrospray ionization-QTOF-mass spectrometry (UPLC-ESI-QTOF-MS) combined with multivariate data analysis, including principal component analysis (PCA) and (orthogonal) partial least squared discriminant analysis [(O)PLS-DA] was applied for the investigation of potential diagnostic biomarkers in plasma of OC patients. Patients with OC could be distinguished from healthy individuals and patients with benign gynecological tumor disease by this method, which shows a significant lipid perturbation in this disease. With the assistance of high resolution and high accuracy of MS and MS/MS data, the potential markers including lysophosphatidylcholines (LPCs), phosphatidylcholines (PCs) and triacylglycerols (TGs) with specific fatty acid chains, were identified. Interestingly, LPCs were up-regulated and PCs and TGs were down-regulated, compared OC group with benign tumor and normal control groups, and the glycerophospholipid metabolism emerged as a key pathway, in particular, the phospholipase A2 (PLA2) enzyme activity, that was disregulated in the disease. This study may provide new insight into underlying mechanisms for OC and proves that MS-based lipidomics is a powerful method in discovering new potential clinical biomarkers for diseases.