EZH2 RIP-seq Identifies Tissue-specific Long Non-coding RNAs.

BackgroundPolycomb Repressive Complex 2 (PRC2) catalyzes histone methylation at H3 Lys27, and plays crucial roles during development and diseases in numerous systems. Its catalytic subunit EZH2 represents a key nuclear target for long non-coding RNAs (lncRNAs) that emerging to be a novel class of epigenetic regulator and participate in diverse cellular processes. LncRNAs are characterized by high tissue-specificity; however, little is known about the tissue profile of the EZH2- interacting lncRNAs.ObjectiveHere we performed a global screening for EZH2-binding lncRNAs in tissues including brain, lung, heart, liver, kidney, intestine, spleen, testis, muscle and blood by combining RNA immuno- precipitation and RNA sequencing. We identified 1328 EZH2-binding lncRNAs, among which 470 were shared in at least two tissues while 858 were only detected in single tissue. An RNA motif with specific secondary structure was identified in a number of lncRNAs, albeit not in all EZH2-binding lncRNAs. The EZH2-binding lncRNAs fell into four categories including intergenic lncRNA, antisense lncRNA, intron-related lncRNA and promoter-related lncRNA, suggesting diverse regulations of both cis and trans-mechanisms. A promoter-related lncRNA Hnf1aos1 bound to EZH2 specifically in the liver, a feature same as its paired coding gene Hnf1a, further confirming the validity of our study. In addition to the well known EZH2-binding lncRNAs like Kcnq1ot1, Gas5, Meg3, Hotair and Malat1, majority of the lncRNAs were firstly reported to be associated with EZH2.ConclusionOur findings provide a profiling view of the EZH2-interacting lncRNAs across different tissues, and suggest critical roles of lncRNAs during cell differentiation and maturation

Trends and impact factors of mental health service utilization among resettled humanitarian migrants in Australia : findings from the BNLA cohort study

Resettled humanitarian migrants (HMs) have high levels of mental disorders, but factors associated with the utilization of mental health services (MHS) are poorly understood. We aimed to explore trends and impact factors of MHS utilization among HMs in the process of resettlement in Australia. A total of 2311 HMs from the 1st (2013), 3rd, and 5th (2018) waves of a national cohort study were included. MHS utilization in the past year was assessed by two indicators: having MHS contacts and the frequency of MHS contacts. Trends were identified by Cochran-Armitage tests, and generalized linear mixed models and ordered logistic models were fitted to explore impact factors of MHS utilization. The proportion of having MHS contacts significantly rose from 13.0% to 29.4% over the five years. MHS utilization was mainly driven by perceived needs, such as post-traumatic stress disorders and the degree of post-migration stress. Unemployment and strong belongingness to the local community were also associated with having MHS contacts. No significant gender difference was found in having MHS contacts but females tended to contact MHS more frequently. Resettled HMs have a persistent dilemma of high mental illness prevalence and MHS underutilization. Sustainable mental health education and long-term resettlement services targeted at social integration that consider gender difference are urgently needed in host countries

Antiaging Effect of Pine Pollen in Human Diploid Fibroblasts and in a Mouse Model Induced by D-Galactose

The present paper was designed to investigate the effect of pine pollen against aging in human diploid fibroblast 2BS cells and in an accelerated aging model, which was established by subcutaneous injections with D-galactose daily for 8 weeks in C57BL/6J mice. Pine pollen (1 mg/mL and 2 mg/mL) is proved to delay the replicative senescence of 2BS cells as evidenced by enhanced cell proliferation, decreased SA-β-Gal activity, and reversed expression of senescence-associated molecular markers, such as p53, p21Waf1, p16INK4a, PTEN, and p27Kip1 in late PD cells. Besides, pine pollen reversed D-galactose-induced aging effects in neural activity and inflammatory cytokine levels, as indicated by improved memory latency time and reduced error rate in step-down test and decreased concentrations of IL-6 and TNF-α in model mice. Similar to the role of AGEs (advanced glycation endproducts) formation inhibitor aminoguanidine (AG), pine pollen inhibited D-galactose-induced increment of AGEs levels thus reversed the aging phenotypes in model mice. Furthermore, the declined antioxidant activity was obviously reversed upon pine pollen treatment, which may account for its inhibitory effect on nonenzymatic glycation (NEG) in vivo. Our finding presents pine pollen as an attractive agent with potential to retard aging and attenuate age-related diseases in humans

Changes in the bacterial community structure and diversity during bamboo retting

Microbial retting is a critical step in obtaining fiber bundles from bamboo culm using indigenous microorganisms. A cultivation-independent technique for monitoring the changes in bacteria community during bamboo retting was applied in this work. This technique involves genetic profiling of PCR-amplified small-subunit rRNA and the single-strand conformation polymorphism (SSCP) gel analysis of the PCR-amplified 16S rDNA fragments. The study revealed that both the structure and the diversity of investigated communities varied with the incubation periods and sample locations. The bacteria bands from SCCP gel profiles related to Bacillus sp. decreased in intensity, and Phaeospirillum sp. and Azospirillum brasilense completely disappeared during the 4th and 5th month of incubation, while the bands related to the Sphingomonas japonica, Alphaproteobacterium Ellin335 and Microbacterium sp. increased. The bands closely related to Sphingomonads, Brevundimonas brasilense, Pseudoclavibacter sp., Agrococcus jenensis and Oxalophagus oxalicus remained dominant during the whole incubation period. This study showed that the use of PCR assay targeting 16S rRNA and SCCP profiling provided valuable information on monitoring the bacteria dynamic changes occurring in the bacteria community during bamboo retting, which is crucial for controlling the quality of the retting process and improving the retting efficiency, and thus benefits for fiber recovery.This work was made possible by the support from the earmarked fund for Modern Agro-industry Technology Research System (nycytx-19-E23), the European Union Biorenew Project [Sixth Framework Programme (FP6-2004-NMP-NI-4)] and China Scholarship Council. The authors would like to thank Florian Schmid, Herbert Pobeheim, Stefan Wei\l=ss\, Michael Furnkranz, Christoph Schmidt and Endry Nugroho Prasetyo for a number of insightful comments and suggestions

Sonic Hedgehog Signaling Pathway Mediates Proliferation and Migration of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via MAPK/ERK Signaling Pathway

Fibroblast-like synoviocytes (FLSs) are the major effector cells that lead to rheumatoid arthritis (RA) synovitis and joint destruction. Our previous studies showed that Sonic Hedgehog (SHH) signaling pathway is involved in aberrant activation of RA-FLSs and inhibition of SHH pathway decreases proliferation and migration of RA-FLSs. The objective of this study was to investigate if the SHH pathway mediates proliferation and migration of RA-FLSs via the mitogen-activated protein kinases/extracellular signal-regulated kinases (MAPK/ERK) signaling pathway. SHH signaling was studied by using SHH agonist (Purmorphamine) and antagonist (Cyclopamine) targeting the Smoothened (SMO) in FLSs. U0126-EtOH was used to inhibit the MAPK/ERK signaling pathway. The phosphorylation of ERK 1/2 (p-ERKl/2) was examined by western blot. Cell viability was detected using cell proliferation and cytotoxicity kit-8 (CCK8), and cell cycle distribution and proliferating cells were evaluated by the flow cytometry. Cell migration was examined by Transwell assay. Results showed that, compared with the control group, Purmorphamine increased the levels of p-ERK1/2 in concentration-and time-dependent manners (P < 0.01). Co-treated with Purmorphamine and U0126-EtOH or Cyclopamine both decreased the levels of p-ERK1/2 (P < 0.05). RA-FLSs treated with Purmorphamine resulted in alteration of cell cycle distribution, increasing of proliferating cells, cell viability, and migration cells compared to controls (P < 0.01). However, the above phenomenon can be abolished by U0126-EtOH (P < 0.05). The findings suggest that SHH signaling pathway mediates proliferation and migration of RA-FLSs via MAPK/ERK pathway and may contribute to progression of RA. Targeting SHH signaling may have a therapeutic potential in patients with RA

Evolution of the Cultural Trade Network in “the Belt and Road” Region: Implication for Global Cultural Sustainability

While there has been increasing concern with respect to the sustainable development of “the Belt and Road” region, the majority of studies have focused on economic and environmental dimensions. This paper focuses on the temporal cultural trade network between the 66 countries of this region between 1990 and 2016. A social network analysis method was used to analyze the cultural trade network and its temporal evolution, where results detected key nodes and cultural corridors. Furthermore, the conceptual point-line-polygon model, which summarizes the expansion of such cultural nodes and corridors between 1990 and 2016, reveals the rapid development of cultural exchanges within the region. Here, the varied roles of large and small-sized countries were found to be dominated by China, Russia, and India. While the cultural trade network has promoted the integration of cultural diversity into the global market, to achieve global cultural sustainability more active trading relations with small-sized countries should be encouraged

Chromogranin A (CgA) as Poor Prognostic Factor in Patients with Small Cell Carcinoma of the Cervix: Results of a Retrospective Study of 293 Patients

BACKGROUND: Small cell carcinoma of the cervix (SCCC) is a very rare tumor. Due to its rarity and the long time period, there is a paucity of information pertaining to prognostic factors associated with survival. The objective of this study was to determine whether clinicopathologic finings or immunohistochemical presence of molecular markers predictive of clinical outcome in patients with SCCC. METHODOLOGY AND FINDINGS: We retrospectively reviewed a total of 293 patients with SCCC (47 patients from Cancer Center of Sun Yat-sen University in china, 71 patients from case report of china journal, 175 patients from case report in PubMed database). Of those 293 patients with SCCC, the median survival time is 23 months. The 3-year overall survival rates (OS) and 3-year disease-free survival rates (DFS) for all patients were 34.5% and 31.1%, respectively. Univariate and multivariate analysis showed that FIGO stage (IIb-IV VS I-IIa, Hazard Ratio (HR) = 3.08, 95% confidence interval (CI) of ratio = [2.05, 4.63], P<0.001), tumor mass size (≥ 4 cm VS <4 cm, HR = 2.37, 95% CI = [1.28, 4.36], P = 0.006) and chromogranin A (CgA) (Positive VS Negative, HR = 1.81, 95% CI = [1.12, 2.91], P = 0.015) were predictive of poor prognosis. CgA stained positive was found to be highly predictive of death in early-stage (FIGO I-IIa) patient specifically. CONCLUSIONS: Patients with SCCC have poor prognosis. FIGO stage, tumor mass size and CgA stained positive may act as a surrogate for factors prognostic of survival. CgA may serve as a useful marker in prognostic evaluation for early-stage patients with SCCC

An Immune Basis for Lung Parenchymal Destruction in Chronic Obstructive Pulmonary Disease and Emphysema

BACKGROUND: Chronic obstructive pulmonary disease and emphysema are a frequent result of long-term smoking, but the exact mechanisms, specifically which types of cells are associated with the lung destruction, are unclear. METHODS AND FINDINGS: We studied different subsets of lymphocytes taken from portions of human lungs removed surgically to find out which lymphocytes were the most frequent, which cell-surface markers these lymphocytes expressed, and whether the lymphocytes secreted any specific factors that could be associated with disease. We found that loss of lung function in patients with chronic obstructive pulmonary disease and emphysema was associated with a high percentage of CD4(+) and CD8(+) T lymphocytes that expressed chemokine receptors CCR5 and CXCR3 (both markers of T helper 1 cells), but not CCR3 or CCR4 (markers of T helper 2 cells). Lung lymphocytes in patients with chronic obstructive pulmonary disease and emphysema secrete more interferon gamma—often associated with T helper 1 cells—and interferon-inducible protein 10 and monokine induced by interferon, both of which bind to CXCR3 and are involved in attracting T helper 1 cells. In response to interferon-inducible protein 10 and monokine induced by interferon, but not interferon gamma, lung macrophages secreted macrophage metalloelastase (matrix metalloproteinase-12), a potent elastin-degrading enzyme that causes tissue destruction and which has been linked to emphysema. CONCLUSIONS: These data suggest that Th1 lymphoctytes in the lungs of people with smoking-related damage drive progression of emphysema through CXCR3 ligands, interferon-inducible protein 10, and monokine induced by interferon

Observation of an Excited Bc+ State

Using pp collision data corresponding to an integrated luminosity of 8.5 fb-1 recorded by the LHCb experiment at center-of-mass energies of s=7, 8, and 13 TeV, the observation of an excited Bc+ state in the Bc+π+π- invariant-mass spectrum is reported. The observed peak has a mass of 6841.2±0.6(stat)±0.1(syst)±0.8(Bc+) MeV/c2, where the last uncertainty is due to the limited knowledge of the Bc+ mass. It is consistent with expectations of the Bc∗(2S31)+ state reconstructed without the low-energy photon from the Bc∗(1S31)+→Bc+γ decay following Bc∗(2S31)+→Bc∗(1S31)+π+π-. A second state is seen with a global (local) statistical significance of 2.2σ (3.2σ) and a mass of 6872.1±1.3(stat)±0.1(syst)±0.8(Bc+) MeV/c2, and is consistent with the Bc(2S10)+ state. These mass measurements are the most precise to date

Measurement of the Forward-Backward Asymmetry in the B -> K(*) mu+ mu- Decay and First Observation of the Bs -> phi mu+ mu- Decay

We reconstruct the rare decays $B^+ \to K^+\mu^+\mu^-$, $B^0 \to K^{*}(892)^0\mu^+\mu^-$, and $B^0_s \to \phi(1020)\mu^+\mu^-$ in a data sample corresponding to $4.4 {\rm fb^{-1}}$ collected in $p\bar{p}$ collisions at $\sqrt{s}=1.96 {\rm TeV}$ by the CDF II detector at the Fermilab Tevatron Collider. Using $121 \pm 16$ $B^+ \to K^+\mu^+\mu^-$ and $101 \pm 12$ $B^0 \to K^{*0}\mu^+\mu^-$ decays we report the branching ratios. In addition, we report the measurement of the differential branching ratio and the muon forward-backward asymmetry in the $B^+$ and $B^0$ decay modes, and the $K^{*0}$ longitudinal polarization in the $B^0$ decay mode with respect to the squared dimuon mass. These are consistent with the theoretical prediction from the standard model, and most recent determinations from other experiments and of comparable accuracy. We also report the first observation of the $B^0_s \to \phi\mu^+\mu^- decay and measure its branching ratio${\mathcal{B}}(B^0_s \to \phi\mu^+\mu^-) = [1.44 \pm 0.33 \pm 0.46] \times 10^{-6}$using$27 \pm 6$signal events. This is currently the most rare$B^0_s$ decay observed.Comment: 7 pages, 2 figures, 3 tables. Submitted to Phys. Rev. Let