Mining Large-scale Event Knowledge from Web Text

AbstractThis paper addresses the problem of automatic acquisition of semantic relations between events. While previous works on semantic relation automatic acquisition relied on annotated text corpus, it is still unclear how to develop more generic methods to meet the needs of identifying related event pairs and extracting event-arguments (especially the predicate, subject and object). Motivated by this limitation, we develop a three-phased approach that acquires causality from the Web text. First, we use explicit connective markers (such as “because”) as linguistic cues to discover causal related events. Next, we extract the event-arguments based on local dependency parse trees of event expressions. At the last step, we propose a statistical model to measure the potential causal relations. The results of our empirical evaluations on a large-scale Web text corpus show that (a) the use of local dependency tree extensively improves both the accuracy and recall of event-arguments extraction task, and (b) our measure improves the traditional PMI method

(Arg) 9 -SH2 superbinder: A novel promising anticancer therapy to melanoma by blocking phosphotyrosine signaling

Background: Melanoma is a malignant tumor with high misdiagnosis rate and poor prognosis. The bio-targeted therapy is a prevailing method in the treatment of melanoma; however, the accompanying drug resistance is inevitable. SH2 superbinder, a triple-mutant of the Src Homology 2 (SH2) domain, shows potent antitumor ability by replacing natural SH2-containing proteins and blocking multiple pY-based signaling pathways. Polyarginine (Arg) 9 , a powerful vector for intracellular delivery of large molecules, could transport therapeutic agents across cell membrane. The purpose of this study is to construct (Arg) 9 -SH2 superbinder and investigate its effects on melanoma cells, expecting to provide potential new approaches for anti-cancer therapy and overcoming the unavoidable drug resistance of single-targeted antitumor agents. Methods: (Arg) 9 and SH2 superbinder were fused to form (Arg) 9 -SH2 superbinder via genetic engineering. Pull down assay was performed to identify that (Arg) 9 -SH2 superbinder could capture a wide variety of pY proteins. Immunofluorescence was used to detect the efficiency of (Arg) 9 -SH2 superbinder entering cells. The proliferation ability was assessed by MTT and colony formation assay. In addition, wound healing and transwell assay were performed to evaluate migration of B16F10, A375 and A375/DDP cells. Moreover, apoptosis caused by (Arg) 9 -SH2 superbinder was analyzed by flow cytometry-based Annexin V/PI. Furthermore, western blot revealed that (Arg) 9 -SH2 superbinder influenced some pY-related signaling pathways. Finally, B16F10 xenograft model was established to confirm whether (Arg) 9 -SH2 superbinder could restrain the growth of tumor. Results: Our data showed that (Arg) 9 -SH2 superbinder had the ability to enter melanoma cells effectively and displayed strong affinities for various pY proteins. Furthermore, (Arg) 9 -SH2 superbinder could repress proliferation, migration and induce apoptosis of melanoma cells by regulating PI3K/AKT, MAPK/ERK and JAK/STAT signaling pathways. Importantly, (Arg) 9 -SH2 superbinder could significantly inhibit the growth of tumor in mice. Conclusions: (Arg) 9 -SH2 superbinder exhibited high affinities for pY proteins, which showed effective anticancer ability by replacing SH2-containing proteins and blocking diverse pY-based pathways. The remarkable ability of (Arg) 9 -SH2 superbinder to inhibit cancer cell proliferation and tumor growth might open the door to explore the SH2 superbinder as a therapeutic agent for cancer treatment

Fucoidan Inhibits the Growth of Hepatocellular Carcinoma Independent of Angiogenesis

Some sulphated polysaccharides can bind bFGF but are unable to present bFGF to its high-affinity receptors. Fucoidan, a sulphated polysaccharide purified from brown algae, which has been used as an anticancer drug in traditional Chinese medicine for hundreds of years, exhibits a variety of anticancer effects, including the induction of the apoptosis and autophagy of cancer cells, the inhibition of the growth of cancer cells, the induction of angiogenesis, and the improvement of antitumour immunity. Our research shows that fucoidan dose not inhibit the expressions of VEGF, bFGF, IL-8, and heparanase in HCC cells and/or tumour tissues. Moreover, fucoidan exhibited low affinity for bFGF and could not block the binding of bFGF to heparan sulphated. Although fucoidan had no effect on angiogenesis and apoptosis in vivo, this drug significantly inhibited the tumour growth and the expression of PCNA. These results suggest that fucoidan exhibits an anticancer effect in vivo at least partly through inhibition of the proliferation of HCC cells, although it is unable to suppress the angiogenesis induced by HCC

Evolution of East Asias Arcto-Tertiary relict Euptelea (Eupteleaceae) shaped by Late Neogene vicariance and Quaternary climate change

Background: The evolutionary origin and historical demography of extant Arcto-Tertiary forest species in East Asia is still poorly understood. Here, we reconstructed the evolutionary and population demographic history of the two extant Euptelea species in China (E. pleiosperma) and Japan (E. polyandra). Chloroplast/nuclear DNA sequences and microsatellite loci were obtained from 36 Euptelea populations to explore molecular structure and diversity in relation to past and present distributions based on ecological niche modelling (ENM). Time-calibrated phylogenetic/phylogeographic inferences and niche-identity tests were used to infer the historical process of lineage formation. Results: Euptelea pleiosperma diverged from E. polyandra around the Late Miocene and experienced significant ecological differentiation. A near-simultaneous diversification of six phylogroups occurred during the mid-to-late Pliocene, in response to the abrupt uplift of the eastern Tibetan Plateau and an increasingly cooler and drier climate. Populations of E. pleiosperma seem to have been mostly stationary through the last glacial cycles, while those of E. polyandra reflect more recent climate-induced cycles of range contraction and expansion. Conclusions: Our results illustrate how Late Neogene climatic/tectonic changes promoted speciation and lineage diversification in East Asias Tertiary relict flora. They also demonstrate for the first time a greater variation in such species responses to glacial cycles in Japan when compared to congeners in China.(VLID)193287

TREML2 Mutation Mediate Alzheimer’s Disease Risk by Altering Neuronal Degeneration

A coding missense mutation (rs3747742) in triggering receptor expressed on myeloid cell-like 2 (TREML2) has been recently proposed as an important protective factor against Alzheimer’s disease (AD). However, the link between TREML2 and AD pathology remains unclear. Therefore, we explored the association of TREML2 rs3747742 with cognitive function, neuroimaging biomarkers and cerebrospinal fluid (CSF) biomarkers related to AD, including CSF total-tau (T-tau), phosphor-tau (P-tau), and amyloid-β (Aβ1-42). As for cognitive function, related cognitive scores of Clinical Dementia Rating Sum of Boxes (CDRSB), Alzheimer’s Disease Assessment Scale-cognitive section 11 (ADAS-cog 11), Mini-Mental State Examination (MMSE), and Rey Auditory-Verbal Learning Test (RAVLT) were extracted. We used a multiple linear regression model to examine the association of TREML2 rs3747742 with the baseline variables. Furthermore, we also calculated the change rate of above variables influenced by TREML2 rs3747742 via applying a mixed-effects model over a 4-year follow-up. In this analysis, a total of 1,306 individuals from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database were included. Finally, we observed that only in AD patients, but not in normal controls or mild cognitive impairment (MCI) individuals, TREML2 rs3747742 exhibited a strong association with CSF total-tau levels at baseline (β = -22.1210, p = 0.0166) and 4-year follow-up (β = -0.3961, p = 0.0115). Furthermore, no associations were found with CSF Aβ1-42 levels, P-tau levels, neuroimaging biomarkers and cognitive function neither for baseline variables nor for longitudinal data. Thus, this study indicated that TREML2 mediated the risk of AD through influencing AD-related neurodegeneration (abnormal T-tau levels) but not P-tau levels and Aβ pathology

Copper-Catalyzed Synthesis, Bio-Evaluation, and in Silico Studies of 2-Aryl-N-alkylbenzimidazoles as Neuroprotective Agents

2-aryl-N-alkylbenzimidazole derivatives synthesized by CuI/PPh3 promoted direct coupling of N-alkylbenzimidazoles with aryl bromides. In vitro neurotoxicities of 20 compounds were evaluated, and the neuroprotective abilities of low-neurotoxic compounds (3b, 3g, 3h, 3i, 3j, 3k, 3o, 3q, 3s and 3t) were investigated against toxicity induced by 1-methyl-4-phenylpyridinium ion (MPP+) in SH-SY5Y neuronal cells. In silico studies revealed that compound 3g could have molecule docking with the following proteins: the bone morphogenetic protein receptor type 1B (BMPR1B), human cytochrome P450 1B1(CYP1B1), Metabotropic glutamate receptor 7 (GRM7), histone deacetylase 6 (HDAC6), 5-hydroxytryptamine receptor 5A (HTR5A), human topoisomerase II beta (TOP2B). A molecular docking simulation of model compound 3g and model protein CYP1B1 has been shown