Origin of the different conductive behavior in pentavalent-ion-doped anatase and rutile TiO2_2

The electronic properties of pentavalent-ion (Nb$^{5+}$, Ta$^{5+}$, and I$^{5+}$) doped anatase and rutile TiO$_2$ are studied using spin-polarized GGA+\emph{U} calculations. Our calculated results indicate that these two phases of TiO$_2$ exhibit different conductive behavior upon doping. For doped anatase TiO$_2$, some up-spin-polarized Ti 3\emph{d} states lie near the conduction band bottom and cross the Fermi level, showing an \emph{n}-type half-metallic character. For doped rutile TiO$_2$, the Fermi level is pinned between two up-spin-polarized Ti 3\emph{d} gap states, showing an insulating character. These results can account well for the experimental different electronic transport properties in Nb (Ta)-doped anatase and rutile TiO$_2$.Comment: 4 pages, 5 figure

β-Fluorofentanyls Are pH-Sensitive Mu Opioid Receptor Agonists

The concept recently postulated by Stein and co-workers (Science2017, 355, 966) that mu opioid receptor (MOR) agonists possessing amines with attenuated basicity show pH-dependent activity and can selectively act at damaged, low pH tissues has been additionally supported by in vitro studies reported here. We synthesized and tested analogs of fentanyl possessing one or two fluorine atoms at the beta position of the phenethylamine side chain, with additional fluorines optionally added to the benzene ring of the side chain. These compounds were synthesized in 1 to 3 steps from commercial building blocks. The novel bis-fluorinated analog RR-49 showed superior pH sensitivity, with full efficacy relative to DAMGO, but with 19-fold higher potency (IC50) in a MOR cAMP assay at pH 6.5 versus 7.4. Such compounds hold significant promise as analgesics for inflammatory pain with reduced abuse potential

Discovery and Characterization of Novel GPR39 Agonists Allosterically Modulated by Zinc

In this study, we identified two previously described kinase inhibitors—3-(4-chloro-2-fluorobenzyl)-2-methyl-N-(3-methyl-1H-pyrazol-5-yl)-8-(morpholinomethyl)imidazo[1,2-b]pyridazin-6-amine (LY2784544) and 1H-benzimidazole-4-carboxylic acid, 2-methyl-1-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-6-(4-morpholinyl)- (GSK2636771)—as novel GPR39 agonists by unbiased small-molecule-based screening using a β-arrestin recruitment screening approach (PRESTO-Tango). We characterized the signaling of LY2784544 and GSK2636771 and compared their signaling patterns with a previously described “GPR39-selective” agonist N-[3-chloro-4-[[[2-(methylamino)-6-(2-pyridinyl)-4- pyrimidinyl]amino]methyl]phenyl]methanesulfonamide (GPR39-C3) at both canonical and noncanonical signaling pathways. Unexpectedly, all three compounds displayed probe-dependent and pathway-dependent allosteric modulation by concentrations of zinc reported to be physiologic. LY2784544 and GS2636771 at GPR39 in the presence of zinc were generally as potent or more potent than their reported activities against kinases in whole-cell assays. These findings reveal an unexpected role of zinc as an allosteric potentiator of small-molecule-induced activation of GPR39 and expand the list of potential kinase off-targets to include understudied G protein–coupled receptors

T Oligo-Primed Polymerase Chain Reaction (TOP-PCR): A Robust Method for the Amplification of Minute DNA Fragments in Body Fluids.

Body fluid DNA sequencing is a powerful noninvasive approach for the diagnosis of genetic defects, infectious agents and diseases. The success relies on the quantity and quality of the DNA samples. However, numerous clinical samples are either at low quantity or of poor quality due to various reasons. To overcome these problems, we have developed T oligo-primed polymerase chain reaction (TOP-PCR) for full-length nonselective amplification of minute quantity of DNA fragments. TOP-PCR adopts homogeneous "half adaptor" (HA), generated by annealing P oligo (carrying a phosphate group at the 5' end) and T oligo (carrying a T-tail at the 3' end), for efficient ligation to target DNA and subsequent PCR amplification primed by the T oligo alone. Using DNA samples from body fluids, we demonstrate that TOP-PCR recovers minute DNA fragments and maintains the DNA size profile, while enhancing the major molecular populations. Our results also showed that TOP-PCR is a superior method for detecting apoptosis and outperforms the method adopted by Illumina for DNA amplification

miRNAMap: genomic maps of microRNA genes and their target genes in mammalian genomes

Recent work has demonstrated that microRNAs (miRNAs) are involved in critical biological processes by suppressing the translation of coding genes. This work develops an integrated database, miRNAMap, to store the known miRNA genes, the putative miRNA genes, the known miRNA targets and the putative miRNA targets. The known miRNA genes in four mammalian genomes such as human, mouse, rat and dog are obtained from miRBase, and experimentally validated miRNA targets are identified in a survey of the literature. Putative miRNA precursors were identified by RNAz, which is a non-coding RNA prediction tool based on comparative sequence analysis. The mature miRNA of the putative miRNA genes is accurately determined using a machine learning approach, mmiRNA. Then, miRanda was applied to predict the miRNA targets within the conserved regions in 3′-UTR of the genes in the four mammalian genomes. The miRNAMap also provides the expression profiles of the known miRNAs, cross-species comparisons, gene annotations and cross-links to other biological databases. Both textual and graphical web interface are provided to facilitate the retrieval of data from the miRNAMap. The database is freely available at

Quark models of dibaryon resonances in nucleon-nucleon scattering

We look for $\Delta\Delta$ and $N\Delta$ resonances by calculating $NN$ scattering phase shifts of two interacting baryon clusters of quarks with explicit coupling to these dibaryon channels. Two phenomenological nonrelativistic chiral quark models giving similar low-energy $NN$ properties are found to give significantly different dibaryon resonance structures. In the chiral quark model (ChQM), the dibaryon system does not resonate in the $NN$ $S$-waves, in agreement with the experimental SP07 $NN$ partial-wave scattering amplitudes. In the quark delocalization and color screening model (QDCSM), the $S$-wave NN resonances disappear when the nucleon size $b$ falls below 0.53 fm. Both quark models give an $IJ^P = 03^+$ $\Delta\Delta$ resonance. At $b=0.52$fm, the value favored by baryon spectrum, the resonance mass is 2390 (2420) MeV for the ChQM with quadratic (linear) confinement, and 2360 MeV for the QDCSM. Accessible from the $^3D_3^{NN}$ channel, this resonance is a promising candidate for the known isoscalar ABC structure seen more clearly in the $pn$$\to$$d\pi\pi$ production cross section at 2410 MeV in the recent preliminary data reported by the CELSIUS-WASA Collaboration. In the isovector dibaryon sector, our quark models give a bound or almost bound $^5S_2^{\Delta\Delta}$ state that can give rise to a $^1D_2^{NN}$ resonance. None of the quark models used has bound $N\Delta$ $P$-states that might generate odd-parity resonances.Comment: 14 pages, 6 tables, 6 figures; added supplementary results, added/deleted references, added 1 figur

Brown Fat Paucity Due to Impaired BMP Signaling Induces Compensatory Browning of White Fat

Summary Maintenance of body temperature is essential for survival of homeotherms. Brown adipose tissue (BAT) is a specialized fat tissue that is dedicated to thermoregulation1. Due to its remarkable capacity to dissipate stored energy and its demonstrated presence in adult humans2-5, BAT holds great promise for the treatment of obesity and metabolic syndrome1. Rodent data suggest the existence of two types of brown fat cells: the constitutive BAT (cBAT), which is of embryonic origin and anatomically located in the interscapular region of mice, and the recruitable BAT (rBAT) that resides within white adipose tissue (WAT)6 and skeletal muscle7, that has alternatively been called beige8, brite9, or inducible BAT10. Bone morphogenetic proteins (BMPs) regulate the formation and thermogenic activity of BAT10-12. We here provide evidence for a systemically active regulatory mechanism that serves to control whole body BAT-activity for thermoregulation and energy homeostasis. Genetic ablation of type 1A BMP-receptor (Bmpr1A) in brown adipogenic progenitor cells leads to a severe paucity of cBAT. This in turn increases sympathetic input to WAT, thereby promoting the formation of rBAT within white fat depots. This previously unknown compensatory mechanism, aimed at restoring total brown fat-mediated thermogenic capacity in the body, is sufficient to maintain normal temperature homeostasis and resistance to diet-induced obesity. These data suggest an important physiological cross-talk between the constitutive and recruitable brown fat cells. This sophisticated regulatory mechanism of body temperature may participate in the control of energy balance and metabolic disease

Working memory dysfunctions predict social problem solving skills in schizophrenia

The current study aimed to examine the contribution of neurocognition and social cognition to components of social problem solving. Sixty-seven inpatients with schizophrenia and 31 healthy controls were administrated batteries of neurocognitive tests, emotion perception tests, and the Chinese Assessment of Interpersonal Problem Solving Skills (CAIPSS). MANOVAs were conducted to investigate the domains in which patients with schizophrenia showed impairments. Correlations were used to determine which impaired domains were associated with social problem solving, and multiple regression analyses were conducted to compare the relative contribution of neurocognitive and social cognitive functioning to components of social problem solving. Compared with healthy controls, patients with schizophrenia performed significantly worse in sustained attention, working memory, negative emotion, intention identification and all components of the CAIPSS. Specifically, sustained attention, working memory and negative emotion identification were found to correlate with social problem solving and 1-back accuracy significantly predicted the poor performance in social problem solving. Among the dysfunctions in schizophrenia, working memory contributed most to deficits in social problem solving in patients with schizophrenia. This finding provides support for targeting working memory in the development of future social problem solving rehabilitation interventions. (C) 2014 Elsevier Ireland Ltd. All rights reserved