3-Isopropyl-2-(4-methoxy­phen­oxy)-1-benzo­furo[3,2-d]pyrimidin-4(3H)-one

In the title compound, C20H18N2O4, all non-H atoms of the three fused rings of the benzofuro[3,2-d]pyrimidine system are almost coplanar (r.m.s. deviation 0.021 Å). The dihedral angle between the fused ring system and the benzene ring is 1.47 (12)°. Intra­molecular and inter­molecular C—H⋯O hydrogen bonds together with weak C—H⋯π inter­actions stabilize the structure

The temporal dynamics of attention:Thinking about oneself comes at a cost in sub‐clinical depression but not in healthy participants

Self-relevant stimuli seem to automatically draw attention, but it is unclear whether this comes at a cost for processing subsequent stimuli, and whether the effect is depending on one’s mental state (i.e. depression). To address this question, we performed two experiments. In Experiment 1, 45 participants were to report two words (T1 and T2) in an attentional blink (AB) paradigm. T1 was a personality characteristic varying in self-rated self-relevance, whereas T2 was a neutral word. A generalized linear mixed model (GLMM) was applied to compare the T1 and T2 accuracies when T1 was high or low self-relevant. A positive effect of self-relevance was found on T1, without observable carry-over effects on T2 performance. However, in Experiment 2, a GLMM applied on 93 participants showed that T1 self-relevance can affect T2, showing opposite effects depending on sub-clinical depression score. Our findings imply that people with low depression scores process self-relevant stimuli more efficiently, which is reflected in a reduced AB. In contrast, individuals with higher scores in depression demonstrated a difficulty to withdraw attention from self-relevant information, reflected in an increased AB. Our findings thus reveal that a processing advantage for highly self-relevant stimuli comes at either a subsequent cost or benefit in temporal attention depending on one’s mental disposition

Influence of the Maritime Continent on the Boreal Summer Intraseasonal Oscillation

Abstract The e¤ect of the Maritime Continent (MC) on the propagation characteristics of the boreal summer intraseasonal oscillation (ISO) over the Indo-western Pacific region were investigated by performing high-resolution (T159) atmospheric general circulation model (AGCM) simulations that remove and retain the MC. The most significant di¤erence, as revealed by a finite domain wavenumber-frequency spectral analysis is the weakening of the northward propagation of ISO over the Asian monsoon region (65 -160 E) when the MC is removed; a less significant di¤erence is the enhancement of the eastward propagation along the equator. The diagnosis of the vertical structure of the simulated ISO and the model mean flow indicates that the weakening of the northward propagation is primarily attributed to the reduction of the background easterly shear, low-level southerly and meridional humidity gradient, all of which contribute to the weakening of meridional asymmetries of vorticity and humidity fields with respect to the ISO convection center. The enhanced eastward propagation is possibly attributed to the strengthening of the mean convection over the MC in association with the increase of the local surface moisture and moist static energy

How may tropical cyclones change in a warmer climate?

Tropical Cyclones (TC) under different climate conditions in the Northern Hemisphere have been investigated with the Max Planck Institute (MPI) coupled (ECHAM5/MPIOM) and atmosphere (ECHAM5) climate models. The intensity and size of the TC depend crucially on resolution with higher wind speed and smaller scales at the higher resolutions. The typical size of the TC is reduced by a factor of 2.3 from T63 to T319 using the distance of the maximum wind speed from the centre of the storm as a measure. The full three dimensional structure of the storms becomes increasingly more realistic as the resolution is increased. For the T63 resolution, three ensemble runs are explored for the period 1860 until 2100 using the IPCC SRES scenario A1B and evaluated for three 30 year periods at the end of the 19th, 20th and 21st century, respectively. While there is no significant change between the 19th and the 20th century, there is a considerable reduction in the number of the TC by some 20% in the 21st century, but no change in the number of the more intense storms. Reduction in the number of storms occurs in all regions. A single additional experiment at T213 resolution was run for the two latter 30-year periods. The T213 is an atmospheric only experiment using the transient Sea Surface Temperatures (SST) of the T63 resolution experiment. Also in this case, there is a reduction by some 10% in the number of simulated TC in the 21st century compared to the 20th century but a marked increase in the number of intense storms. The number of storms with maximum wind speeds greater than 50ms-1 increases by a third. Most of the intensification takes place in 2 the Eastern Pacific and in the Atlantic where also the number of storms more or less stays the same. We identify two competing processes effecting TC in a warmer climate. First, the increase in the static stability and the reduced vertical circulation is suggested to contribute to the reduction in the number of storms. Second, the increase in temperature and water vapor provide more energy for the storms so that when favorable conditions occur, the higher SST and higher specific humidity will contribute to more intense storms. As the maximum intensity depends crucially on resolution, this will require higher resolution to have its full effect. The distribution of storms between different regions does not, at first approximation, depend on the temperature itself but on the distribution of the SST anomalies and their influence on the atmospheric circulation. Two additional transient experiments at T319 resolution where run for 20 years at the end of the 20th and 21st century, respectively using the same conditions as in the T213 experiments. The results are consistent with the T213 study. The total number of tropical cyclones were similar to the T213 experiment but were generally more intense. The change from the 20th to the 21st century was also similar with fewer TC in total but with more intense cyclones

Chronic Voluntary Alcohol Drinking Causes Anxiety-Like Behavior, Thiamine Deficiency, and Brain Damage of Female Crossed High Alcohol Preferring Mice

The central nervous system is vulnerable to chronic alcohol abuse, and alcohol dependence is a chronically relapsing disorder which causes a variety of physical and mental disorders. Appropriate animal models are important for investigating the underlying cellular and molecular mechanisms. The crossed High Alcohol Preferring mice prefer alcohol to water when given free access. In the present study, we used female cHAP mice as a model of chronic voluntary drinking to evaluate the effects of alcohol on neurobehavioral and neuropathological changes. The female cHAP mice had free-choice access to 10% ethanol and water, while control mice had access to water alone at the age of 60-day-old. The mice were exposed to alcohol for 7 months then subjected to neurobehavioral tests including open field (OF), elevated plus maze (EPM), and Morris water maze (MWM). Results from OF and EPM tests suggested that chronic voluntary drinking caused anxiety-like behaviors. After behavior tests, mice were sacrificed, and brain tissues were processed for biochemical analyses. Alcohol altered the levels of several neurotransmitters and neurotrophic factors in the brain including gamma-Aminobutyric acid (GABA), corticotropin-releasing factor, cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor. Alcohol increased the expression of neuroinflammation markers including interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and C-C chemokine receptor 2 (CCR2). Alcohol also induced cleaved caspase-3 and glial fibrillary acidic protein, indicative of neurodegeneration and gliosis. In addition, alcohol inhibited the expression of thiamine transporters in the brain and reduced thiamine levels in the blood. Alcohol also caused oxidative stress and endoplasmic reticulum (ER) stress, and stimulated neurogenesis

Phytonutrient genistein is a survival factor for pancreatic β-cells via GPR30-mediated mechanism

We previously discovered that phytonutrient genistein rapidly activates cAMP signaling in β-cells and improves islet mass in diabetic mice. However, the mechanism underlying these actions of genistein is still unclear. Here, we show that pharmacological or molecular inhibition of Gαs blocked genistein-stimulated adenylate cyclase activity in plasma membrane and intracellular cAMP production in INS1 cells and islets. Further, genistein stimulation of cAMP generation was abolished in islets exposed to a specific GPR30 inhibitor G15 or islets from GPR30 deficient (GPR30−/−) mice. In vivo, dietary provision of genistein (0.5 g/kg diet) significantly mitigated streptozotocin-induced hyperglycemia in male WT mice, which was associated with improved blood insulin levels and pancreatic islet mass and survival, whereas these effects were absent in Gpr30−/− mice. Genistein treatment promoted survival of INS1 cells and human islets chronically exposed to palmitate and high glucose. At molecular level, genistein activated CREB phosphorylation and subsequently induced Bcl-2 expression, and knockdown of CREB diminished the protective effect of genistein on β-cells induced by lipoglucotoxicity. Finally, deletion of GPR30 in β-cells or islets ablated genistein-induced CREB phosphorylation and its cytoprotective effect. These findings demonstrate that genistein is a survival factor for β-cells via GPR30-initiated, Gαs-mediated activation of CREB

Effect of estradiol on proliferation and differentiation of side population stem/progenitor cells from murine endometrium

<p>Abstract</p> <p>Background</p> <p>In our previous study, endometrium side population cells (SP cells) were isolated from postpartum murine uterus, and characterized by a heterogeneous population of stem/progenitor cells. In this study, we investigated the effect of estrogen on the proliferation and differentiation of SP cells.</p> <p>Methods</p> <p>SP and non-SP cells of postpartum murine endometrium were isolated by DNA dye Hoechst 33342. The expression of estrogen receptor 1 (ESR1) was measured by reverse transcription polymerase chain reaction (RT-PCR), Real-time PCR, Western blot, immunofluorescence and immunohistochemistry. The proliferation and differentiation of SP cells treated with different concentrations [10(-8) M-10(-6) M] of estradiol (E2) and E2+ ICI182780 (Faslodex, inhibitor of ESR1) were measured by 3-(4, 5-dimethylthiazoly1-2)-2,5-diphenyltetrazolium bromide(MTT) and clonogenic assays.</p> <p>Results</p> <p>(1) SP cells expressed ESR1 at a higher level than non-SP cells. (2) The level of E2 in the serum and the expression of ESR1 in the uterus of postpartum murine changed in the same manner with the ratio of SP cells to total uterus cells at a different postpartum time point. ESR1, as ABCG2 is also predominantly located in the stroma and the glandular epithelium of the uterus. (3) 10(-6) M E2 notably promoted the proliferation of SP cells after treatment for 24 h. This effect could be inhibited by ICI182780. E2 at the concentration of 10(-7) M or 10(-8) M was sent to impair the large cloning efficiency (CE) of SP cells.</p> <p>Conclusions</p> <p>The effect of estrogen on the proliferation and differentiation of endometrium SP cells via ESR1 was observed and it was in a concentration dependent fashion. Clearly, more work is needed to understand the <it>in vivo </it>effect of E2 at the physiological concentration on the differentiation of SP cells.</p

The Role of Autophagy in Parkinson's Disease: Rotenone-Based Modeling

Background: Autophagy-mediated self-digestion of cytoplasmic inclusions may be protective against neurodegenerative diseases such as Parkinson’s disease (PD). However, excessive autophagic activation evokes autophagic programmed cell death. Methods: In this study, we aimed at exploring the role of autophagy in the pathogenesis of rotenone-induced cellular and animal models for PD. Results: Reactive oxygen species over-generation, mitochondrial membrane potential reduction or apoptosis rate elevation occurred in a dose-dependent fashion in rotenone-treated human neuroblastoma cell line SH-SY5Y. The time- and dose-dependent increases in autophagic marker microtubule-associated protein1 light chain 3 (LC3) expression and decreases in autophagic adaptor protein P62 were observed in this cellular model. LC3-positive autophagic vacuoles were colocalized with alpha-synuclein-overexpressed aggregations. Moreover, the number of autophagic vacuoles was increased in rotenone-based PD models in vitro and in vivo. Conclusions: These data, along with our previous finding showing rotenone-induced toxicity was prevented by the autophagy enhancers and was aggravated by the autophagy inhibitors in SH-SY5Y, suggest that autophagy contributes to the pathogenesis of PD, attenuates the rotenone toxicity and possibly represents a new subcellular target for treating PD