SDSS J163459.82+204936.0: A Ringed Infrared-Luminous Quasar with Outflows in both Absorption and Emission Lines

SDSS J1634+2049 is a local (z = 0.1293) infrared-luminous quasar with LIR= 10^11.91 Lsun. We present a detailed multiwavelength study of both the host galaxy and the nucleus. The host galaxy demonstrates violent, obscured star formation activities with SFR ~ 140 Msun yr^-1, estimated from either the PAH emission or IR luminosity. The optical to NIR spectra exhibit a blueshifted narrow cuspy component in Hb, HeI5876,10830 and other emission lines consistently with an offset velocity of ~900 km/s, as well as additional blueshifting phenomena in high-ionization lines , while there exist blueshifted broad absorption lines (BALs) in NaID and HeI*3889,10830, indicative of the AGN outflows producing BALs and emission lines. Constrained mutually by the several BALs with CLOUDY, the physical properties of the absorption-line outflow are derived as follows: 10^4 < n_H <= 10^5 cm^-3, 10^-1.3 <= U <= 10^-0.7 and 10^22.5<= N_H <= 10^22.9 cm^-2 , similar to those derived for the emission-line outflows. The similarity suggests a common origin. Taking advantages of both the absorption lines and outflowing emission lines, we find that the outflow gas is located at a distance of 48 - 65 pc from the nucleus, and that the kinetic luminosity of the outflow is 10^44-10^46 erg s^-1. J1634+2049 has a off-centered galactic ring on the scale of ~ 30 kpc that is proved to be formed by a recent head-on collision by a nearby galaxy. Thus this quasar is a valuable object in the transitional phase emerging out of dust enshrouding as depicted by the co-evolution scenario.Comment: 13 figures, 6 tables; accepted for publication in Ap

N-Cyclo­hexyl-3-(4-hydr­oxy-6-oxo-1,6-dihydro­pyrimidin-5-yl)-3-p-tolyl­propanamide

In the mol­ecule of the title compound, C20H25N3O3, the aromatic rings are oriented at a dihedral angle of 88.36 (3)°. The cyclo­hexane ring adopts a chair conformation. In the crystal structure, inter­molecular N—H⋯O and O—H⋯N hydrogen bonds link the mol­ecules. C—H⋯π inter­actions are also present

Genome-scale MicroRNA target prediction through clustering with Dirichlet process mixture model

Background: MicroRNA regulation is fundamentally responsible for fine-tuning the whole gene network in human and has been implicated in most physiological and pathological conditions. Studying regulatory impact of microRNA on various cellular and disease processes has resulted in numerous computational tools that investigate microRNA-mRNA interactions through the prediction of static binding site highly dependent on sequence pairing. However, what hindered the practical use of such target prediction is the interplay between competing and cooperative microRNA binding that complicates the whole regulatory process exceptionally. Results: We developed a new method for improved microRNA target prediction based on Dirichlet Process Gaussian Mixture Model (DPGMM) using a large collection of molecular features associated with microRNA, mRNA, and the interaction sites. Multiple validations based on microRNA-mRNA interactions reported in recent large-scale sequencing analyses and a screening test on the entire human transcriptome show that our model outperformed several state-of-the-art tools in terms of promising predictive power on binding sites specific to transcript isoforms with reduced false positive prediction. Last, we illustrated the use of predicted targets in constructing conditional microRNA-mediated gene regulation networks in human cancer. Conclusion: The probability-based binding site prediction provides not only a useful tool for differentiating microRNA targets according to the estimated binding potential but also a capability highly important for exploring dynamic regulation where binding competition is involved

2,2,7,7-Tetra­methyl-1,2,3,6,7,8-hexa­hydro­cinnolino[5,4,3-cde]cinnoline

The asymmetric unit of the title compound, C16H20N4, contains two half-mol­ecules, which are completed by crystallographic inversion symmetry. The pyridazine rings are conjugated and the cyclo­hexane rings adopt envelope conformations

Dynamic and Modularized MicroRNA Regulation and Its Implication in Human Cancers

MicroRNA is responsible for the fine-tuning of fundamental cellular activities and human disease development. The altered availability of microRNAs, target mRNAs, and other types of endogenous RNAs competing for microRNA interactions reflects the dynamic and conditional property of microRNA-mediated gene regulation that remains under-investigated. Here we propose a new integrative method to study this dynamic process by considering both competing and cooperative mechanisms and identifying functional modules where different microRNAs co-regulate the same functional process. Specifically, a new pipeline was built based on a meta-Lasso regression model and the proof-of-concept study was performed using a large-scale genomic dataset from ~4,200 patients with 9 cancer types. In the analysis, 10,726 microRNA-mRNA interactions were identified to be associated with a specific stage and/or type of cancer, which demonstrated the dynamic and conditional miRNA regulation during cancer progression. On the other hands, we detected 4,134 regulatory modules that exhibit high fidelity of microRNA function through selective microRNA-mRNA binding and modulation. For example, miR-18a-3p, −320a, −193b-3p, and −92b-3p co-regulate the glycolysis/gluconeogenesis and focal adhesion in cancers of kidney, liver, lung, and uterus. Furthermore, several new insights into dynamic microRNA regulation in cancers have been discovered in this study

The RNA cargo in small extracellular vesicles from chicken eggs is bioactive in C57BL/6J mice and human peripheral blood mononuclear cells \u3ci\u3eex vivo\u3c/i\u3e

Small extracellular vesicles (sEVs) and their RNA cargo in milk are bioavailable in humans, pigs, and mice, and their dietary depletion and supplementation elicits phenotypes. Little is known about the content and biological activity of sEVs in foods of animal origin other than milk. Here we tested the hypothesis that sEVs in chicken eggs (Gallus gallus) facilitate the transfer of RNA cargo from an avian species to humans and mice, and their dietary depletion elicits phenotypes. sEVs were purified from raw egg yolk by ultracentrifugation and authenticated by transmission electron microscopy, nano-tracking device, and immunoblots. The miRNA profile was assessed by RNA-sequencing. Bioavailability of these miRNAs in humans was assessed by egg feeding study in adults, and by culturing human peripheral blood mononuclear cells (PBMCs) with fluorophore-labeled egg sEVs ex vivo. To further assess bioavailability, fluorophore-labeled miRNAs, encapsulated in egg sEVs, were administered to C57BL/6 J mice by oral gavage. Phenotypes of sEV RNA cargo depletion were assessed by feeding egg sEV and RNA-defined diets to mice and using spatial learning and memory in the Barnes and water mazes as experimental readouts. Egg yolk contained 6.30 × 1010 ± 6.06 × 109 sEVs/ mL, which harbored eighty-three distinct miRNAs. Human PBMCs internalized sEVs and their RNA cargo. Egg sEVs, loaded with fluorophore-labeled RNA and administered orally to mice, accumulated primarily in brain, intestine and lungs. Spatial learning and memory (SLM) was compromised in mice fed on egg sEVand RNA-depleted diet compared to controls. Egg consumption elicited an increase of miRNAs in human plasma. We conclude that egg sEVs and their RNA cargo probably are bioavailable. The human study is registered as a clinical trial and accessible at https://www.isrctn.com/ISRCTN77867213

Dietary Depletion of Milk Exosomes and Their MicroRNA Cargos Elicits a Depletion of miR-200a-3p and Elevated Intestinal Inflammation and Chemokine (C-X-C Motif) Ligand 9 Expression in Mdr1a−/− Mice

Background: Exosomes transfer regulatory microRNAs (miRs) from donor cells to recipient cells. Exosomes and miRs originate from both endogenous synthesis and dietary sources such as milk. miR-200a-3p is a negative regulator of the proinflammatory chemokine (C-X-C motif) ligand 9 (CXCL9). Male Mdr1a−/− mice spontaneously develop clinical signs of inflammatory bowel disease (IBD). Objectives: We assessed whether dietary depletion of exosomes and miRs alters the severity of IBD in Mdr1a−/− mice owing to aberrant regulation of proinflammatory cytokines. Methods: Starting at 5 wk of age, 16 male Mdr1a−/− mice were fed either milk exosome– and RNA-sufficient (ERS) or milk exosome– and RNA-depleted (ERD) diets. The ERD diet is characterized by a near-complete depletion of miRs and a 60% loss of exosome bioavailability compared with ERS. Mice were killed when their weight loss exceeded 15% of peak body weight. Severity of IBD was assessed by histopathological evaluation of cecum. Serum cytokine and chemokine concentrations and mRNA and miR tissue expression were analyzed by multiplex ELISAs, RNA-sequencing analysis, and qRT-PCR, respectively. Results: Stromal collapse, gland hyperplasia, and additive microscopic disease scores were (mean ± SD) 56.7% ± 23.3%, 23.5% ± 11.8%, and 29.6% ± 8.2% lower, respectively, in ceca of ERS mice than of ERD mice (P \u3c 0.05). The serum concentration of CXCL9 was 35.0% ± 31.0% lower in ERS mice than in ERD mice (P \u3c 0.05). Eighty-seven mRNAs were differentially expressed in the ceca from ERS and ERD mice; 16 of these mRNAs are implicated in immune function. The concentrations of 4 and 1 out of 5 miRs assessed (including miR-200a-3p) were ≤63% lower in livers and ceca, respectively, from ERD mice than from ERS mice. Conclusions: Milk exosome and miR depletion exacerbates cecal inflammation in Mdr1a−/− mice

N-Cyclo­pentyl-3-(4-hydr­oxy-6-oxo-1,6-dihydro­pyrimidin-5-yl)-3-p-tolyl­propanamide

In the mol­ecule of the title compound, C19H23N3O3, the six-membered rings are oriented at a dihedral angle of 73.06 (3)°. The cyclo­pentyl ring adopts an envelope conformation. In the crystal structure, inter­molecular N—H⋯O and O—H⋯N hydrogen bonds link the mol­ecules. In the tolyl ring, the H atoms and all but one of the C atoms are disordered over two positions and were refined with occupancies of 0.51 (3) and 0.49 (3)

Fe(III)-Catalyzed Bicyclization of Yne-Allenones With Indoles for the Atom-Economic Synthesis of 3-Indolyl Cyclobutarenes

A new Fe(III)-catalyzed bicyclization reaction of yne-allenones with indoles has been established, enabling the direct construction of cyclobuta[a]naphthalen-4-ols with an all-carbon quaternary center in good to excellent yields. This reaction was performed by using low-cost FeCl3 as the catalyst and EtOH as the environmentally benign solvent, providing a green protocol for constructing the cyclobutarene framework with a high degree of atom economy and functional group compatibility. The reaction mechanism was proposed to proceed through a [2 + 2] cycloaddition/1,6-conjugate addition cascade