Mirtazapine exerts an anxiolytic-like effect through activation of the median raphe nucleus-dorsal hippocampal 5-HT pathway in contextual fear conditioning in rats

The functional role of serotonergic projections from the median raphe nucleus (MRN) to the dorsal hippocampus (DH) in anxiety remains understood poorly. The purpose of the present research was to examine the functional role of this pathway, using the contextual fear conditioning (CFC) model of anxiety. We show that intra-MRN microinjection of mirtazapine, a noradrenergic and specific serotonergic antidepressant, reduced freezing in CFC without affecting general motor activity dose-dependently, suggesting an anxiolytic-like effect. In addition, intra-MRN microinjection of mirtazapine dose-dependently increased extracellular concentrations of serotonin (5-HT) but not dopamine in the DH. Importantly, intra-DH pre-microinjection of WAY-100635, a 5-HT1A antagonist, significantly attenuated the effect of mirtazapine on freezing. These results, for the first time, suggest that activation of the MRN-DH 5-HT1A pathway exerts an anxiolytic-like effect in CFC. This is consistent with the literature that the hippocampus is essential for retrieval of contextual memory and that 5-HT1A receptor activation in the hippocampus primarily exerts an inhibitory effect on the neuronal activity

Acquired craniomeningocele in an infant with craniosynostosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Craniosynostosis can affect the skull in various ways. The most common forms are abnormal skull shape and beaten copper pattern, while Lückenschädel (or lacunar skull) is one of the least common forms.</p> <p>Case presentation</p> <p>We report the case of a 3-month-old Caucasian boy with multiple suture craniosynostosis and with acquired craniomeningocele presenting as a bulging mass in the lateral occipital area.</p> <p>Conclusion</p> <p>To the best of our knowledge, this is the first report of a patient with multiple suture craniosynostosis and acquired craniomeningocele.</p

High-efficiency photovoltaic cells with wide optical band gap polymers based on fluorinated phenylene-alkoxybenzothiadiazole

A series of semi-crystalline, wide band gap (WBG) photovoltaic polymers were synthesized with varying number and topology of fluorine substituents. To decrease intramolecular charge transfer and to modulate the resulting band gap of D-A type copolymers, electron-releasing alkoxy substituents were attached to electron-deficient benzothiadiazole (A) and electron-withdrawing fluorine atoms (0-4F) were substituted onto a 1,4-bis(thiophen-2-yl)benzene unit (D). Intra- and/or interchain noncovalent Coulombic interactions were also incorporated into the polymer backbone to promote planarity and crystalline intermolecular packing. The resulting optical band gap and the valence level were tuned to 1.93-2.15 eV and -5.37 to -5.67 eV, respectively, and strong interchain organization was observed by differential scanning calorimetry, high-resolution transmission electron microscopy and grazing incidence X-ray scattering measurements. The number of fluorine atoms and their position significantly influenced the photophysical, morphological and optoelectronic properties of bulk heterojunctions (BHJs) with these polymers. BHJ photovoltaic devices showed a high power conversion efficiency (PCE) of up to 9.8% with an open-circuit voltage of 0.94-1.03 V. To our knowledge, this PCE is one of the highest values for fullerene-based single BHJ devices with WBG polymers having a band gap of over 1.90 eV. A tandem solar cell was also demonstrated successfully to show a PCE of 10.3% by combining a diketopyrrolopyrrole-based low band gap polymer

Chemistry-driven changes strongly influence climate forcing from vegetation emissions

Biogenic volatile organic compounds (BVOCs) affect climate via changes to aerosols, aerosol-cloud interactions (ACI), ozone and methane. BVOCs exhibit dependence on climate (causing a feedback) and land use but there remains uncertainty in their net climatic impact. One factor is the description of BVOC chemistry. Here, using the earth-system model UKESM1, we quantify chemistry’s influence by comparing the response to doubling BVOC emissions in the pre-industrial with standard and state-of-science chemistry. The net forcing (feedback) is positive: ozone and methane increases and ACI changes outweigh enhanced aerosol scattering. Contrary to prior studies, the ACI response is driven by cloud droplet number concentration (CDNC) reductions from suppression of gas-phase SO2 oxidation. With state-of-science chemistry the feedback is 43% smaller as lower oxidant depletion yields smaller methane increases and CDNC decreases. This illustrates chemistry’s significant influence on BVOC’s climatic impact and the more complex pathways by which BVOCs influence climate than currently recognised

Transactivation of EGFR by LPS induces COX-2 expression in enterocytes

Necrotizing enterocolitis (NEC) is the leading cause of gastrointestinal morbidity and mortality in preterm infants. NEC is characterized by an exaggerated inflammatory response to bacterial flora leading to bowel necrosis. Bacterial lipopolysaccharide (LPS) mediates inflammation through TLR4 activation and is a key molecule in the pathogenesis of NEC. However, LPS also induces cyclooxygenase-2 (COX-2), which promotes intestinal barrier restitution through stimulation of intestinal cell survival, proliferation, and migration. Epidermal growth factor receptor (EGFR) activation prevents experimental NEC and may play a critical role in LPS-stimulated COX-2 production. We hypothesized that EGFR is required for LPS induction of COX-2 expression. Our data show that inhibiting EGFR kinase activity blocks LPS-induced COX-2 expression in small intestinal epithelial cells. LPS induction of COX-2 requires Src-family kinase signaling while LPS transactivation of EGFR requires matrix metalloprotease (MMP) activity. EGFR tyrosine kinase inhibitors block LPS stimulation of mitogen-activated protein kinase ERK, suggesting an important role of the MAPK/ERK pathway in EGFR-mediated COX-2 expression. LPS stimulates proliferation of IEC-6 cells, but this stimulation is inhibited with either the EGFR kinase inhibitor AG1478, or the selective COX-2 inhibitor Celecoxib. Taken together, these data show that EGFR plays an important role in LPS-induction of COX-2 expression in enterocytes, which may be one mechanism for EGF in inhibition of NEC

High-throughput in vivo vertebrate screening

We demonstrate a high-throughput platform for cellular-resolution in vivo chemical and genetic screens on zebrafish larvae. The system automatically loads zebrafish from reservoirs or multiwell plates, and positions and rotates them for high-speed confocal imaging and laser manipulation of both superficial and deep organs within 19 s without damage. We performed small-scale test screening of retinal axon guidance mutants and neuronal regeneration assays in combination with femtosecond laser microsurgery.National Institutes of Health (U.S.) (Director’s Innovator Award 1-DP2-OD002989–01)David & Lucile Packard Foundation (Award in Science and Engineering)Alfred P. Sloan Foundation (Award)Broad Institute of MIT and Harvard (Sparc Grant)National Science Foundation (U.S.) (Fellowship)Foxconn (Sponsorship