Translational control of depression-like behavior via phosphorylation of eukaryotic translation initiation factor 4E

Translation of mRNA into protein has a fundamental role in neurodevelopment, plasticity, and memory formation; however, its contribution in the pathophysiology of depressive disorders is not fully understood. We investigated the involvement of MNK1/2 (MAPK-interacting serine/threonine-protein kinase 1 and 2) and their target, eIF4E (eukaryotic initiation factor 4E), in depression-like behavior in mice. Mice carrying a mutation in eIF4E for the MNK1/2 phosphorylation site (Ser209Ala, Eif4e ki/ki), the Mnk1/2 double knockout mice (Mnk1/2 -/-), or mice treated with the MNK1/2 inhibitor, cercosporamide, displayed anxiety-and depression-like behaviors, impaired serotonin-induced excitatory synaptic activity in the prefrontal cortex, and diminished firing of the dorsal raphe neurons. In Eif4e ki/ki mice, brain IκBα, was decreased, while the NF-κB target, TNFα was elevated. TNFα inhibition in Eif4e ki/ki mice rescued, whereas TNFα administration to wild-type mice mimicked the depression-like behaviors and 5-HT synaptic deficits. We conclude that eIF4E phosphorylation modulates depression-like behavior through regulation of inflammatory responses

Identification of six new susceptibility loci for invasive epithelial ovarian cancer.

Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 ] HEALTH ]F2 ]2009 ]223175). The CIMBA data management and data analysis were supported by Cancer Research.UK grants 12292/A11174 and C1287/A10118. The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scientific development and funding for this project were in part supported by the US National Cancer Institute GAME ]ON Post ]GWAS Initiative (U19 ]CA148112). This study made use of data generated by the Wellcome Trust Case Control consortium. Funding for the project was provided by the Wellcome Trust under award 076113. The results published here are in part based upon data generated by The Cancer Genome Atlas Pilot Project established by the National Cancer Institute and National Human Genome Research Institute (dbGap accession number phs000178.v8.p7). The cBio portal is developed and maintained by the Computational Biology Center at Memorial Sloan ] Kettering Cancer Center. SH is supported by an NHMRC Program Grant to GCT. Details of the funding of individual investigators and studies are provided in the Supplementary Note. This study made use of data generated by the Wellcome Trust Case Control consortium, funding for which was provided by the Wellcome Trust under award 076113. The results published here are, in part, based upon data generated by The Cancer Genome Atlas Pilot Project established by the National Cancerhttp://dx.doi.org/10.1038/ng.3185This is the Author Accepted Manuscript of 'Identification of six new susceptibility loci for invasive epithelial ovarian cancer' which was published in Nature Genetics 47, 164–171 (2015) © Nature Publishing Group - content may only be used for academic research

Effects of leachates from UV-weathered microplastic on the microalgae Scenedesmus vacuolatus

publishedVersio

Circulating and broncho-alveolar interleukin-6 in relation to body temperature in an experimental model of bovine Chlamydia psittaci infection.

In rodent models of experimentally induced fever, the important role of interleukin-6 (IL-6) as a circulating endogenous pyrogen is well established. Studies employing larger animal species and real infections are scarce. Therefore, we assessed bioactive IL-6 in peripheral blood and in broncho-alveolar lavage fluid (BALF) of calves after intra-bronchial inoculation with vital Chlamydia psittaci (Cp), with inactivated Cp, or with BGM cells. Only calves inoculated with vital Cp developed fever (peak at 2-3 days after challenge) and significantly increased IL-6 activity. Controls inoculated with either inactivated Cp or BGM cells also expressed increased bioactive IL-6, but no fever developed. Activity of IL-6 in BALF was significantly higher compared to blood serum. This experimental model of Cp infection revealed no apparent relation between IL-6 in blood and body temperature, but did reveal a relation between IL-6 and other markers of inflammation in BALF. We conclude that a local inflammatory response in the lungs of infected calves caused fever, which developed by mechanisms including other mediators besides IL-6

Effects of leachates from UV-weathered microplastic on the microalgae Scenedesmus vacuolatus

Plastics undergo successive fragmentation and chemical leaching steps in the environment due to weathering processes such as photo-oxidation. Here, we report the effects of leachates from UV-irradiated microplastics towards the chlorophyte Scenedesmus vacuolatus. The microplastics tested were derived from an additive-containing electronic waste (EW) and a computer keyboard (KB) as well as commercial virgin polymers with low additive content, including polyethylene (PE), polyethylene terephthalate (PET), polypropylene (PP), and polystyrene (PS). Whereas leachates from additive-containing EW and KB induced severe effects, the leachates from virgin PET, PP, and PS did not show substantial adverse effects in our autotrophic test system. Leachates from PE reduced algae biomass, cell growth, and photosynthetic activity. Experimental data were consistent with predicted effect concentrations based on the ionization-corrected liposome/water distribution ratios (Dlip/w) of polymer degradation products of PE (mono- and dicarboxylic acids), indicating that leachates from weathering PE were mainly baseline toxic. This study provides insight into algae toxicity elicited by leachates from UV-weathered microplastics of different origin, complementing the current particle- vs. chemical-focused research towards the toxicity of plastics and their leachates

Study design.

<p>d ai/h ai = days/hours ante inoculation; dpi = days post inoculation.</p

Plastic ingestion by pelagic and demersal fish from the North Sea and Baltic Sea

Plastic ingestion by marine biota has been reported for a variety of different taxa. In this study, we investigated 290 gastrointestinal tracts of demersal (cod, dab and flounder) and pelagic fish species (herring and mackerel) from the North and Baltic Sea for the occurrence of plastic ingestion. In 5.5% of all investigated fishes, plastic particles were detected, with 74% of all particles being in the microplastic (< 5 mm) size range. The polymer types of all found particles were analysed by means of Fourier transform infrared (FT-IR) spectroscopy. Almost 40% of the particles consisted of polyethylene (PE). In 3.4% of the demersal and 10.7% of the pelagic individuals, plastic ingestion was recorded, showing a significantly higher ingestion frequency in the pelagic feeders. The condition factor K was calculated to test differences in the fitness status between individuals with and without ingested plastic, but no direct effect was detecte

Study design.

<p>d ai/h ai = days/hours ante inoculation; dpi = days post inoculation.</p