Activation of interferon regulatory factor-3 via toll-like receptor 3 and immunomodulatory functions detected in A549 lung epithelial cells exposed to misplaced U1-snRNA

U1-snRNA is an integral part of the U1 ribonucleoprotein pivotal for pre-mRNA splicing. Toll-like receptor (TLR) signaling has recently been associated with immunoregulatory capacities of U1-snRNA. Using lung A549 epithelial/carcinoma cells, we report for the first time on interferon regulatory factor (IRF)-3 activation initiated by endosomally delivered U1-snRNA. This was associated with expression of the IRF3-inducible genes interferon-β (IFN-β), CXCL10/IP-10 and indoleamine 2,3-dioxygenase. Mutational analysis of the U1-snRNA-activated IFN-β promoter confirmed the crucial role of the PRDIII element, previously proven pivotal for promoter activation by IRF3. Notably, expression of these parameters was suppressed by bafilomycin A₁, an inhibitor of endosomal acidification, implicating endosomal TLR activation. Since resiquimod, an agonist of TLR7/8, failed to stimulate A549 cells, data suggest TLR3 to be of prime relevance for cellular activation. To assess the overall regulatory potential of U1-snRNA-activated epithelial cells on cytokine production, co-cultivation with peripheral blood mononuclear cells (PBMC) was performed. Interestingly, A549 cells activated by U1-snRNA reinforced phytohemagglutinin-induced interleukin-10 release by PBMC but suppressed that of tumor necrosis factor-α, indicating an anti-inflammatory potential of U1-snRNA. Since U1-snRNA is enriched in apoptotic bodies and epithelial cells are capable of performing efferocytosis, the present data in particular connect to immunobiological aspects of apoptosis at host/environment interfaces.     

Dinophyte chloroplasts and phylogeny - A review

Dinophytes acquired chloroplasts obviously early in evolution and later lost them multiple times. Most families and genera contain both photosynthetic and heterotrophic species. Chloroplasts enveloped by three membranes with thylakoids in stacks of three, containing peridinin as the main pigment, are regarded as the original dinophyte plastids. Pyrenoids are generally present. Stigmata, if present, are usually parts of the chloroplast or are modified original plastids. The form II type RUBISCO found in the dinophytes is unique for eukaryotes, otherwise known only in some anaerobic bacteria. It is disputed whether the original dinophyte chloroplasts are derived from a prokaryotic or an eukaryotic endosymbiosis. Various dinoflagellates contain aberrant chloroplasts. Glenodinium foliaceum and Peridinium balticum have a single complete endosymbiont, originally a pcnnate diatom. Podolampas bipes houses several dictyophycean symbiont cells. The “symbionts” of Lepidodiniurn viride and Gymnodinium chlorophorum are highly reduced prasinophyte cells. The chloroplasts of Gymnodinium mikimotoi have aberrant pigments (fucoxanthin derivatives, no peridinin) and fine structure. The dinoflagellate hosts do not seem to contain any parts of the former endosymbiont except the chloroplasts. Photosynthetic Dinophysis species have cryptophycean-like chloroplasts, whereas symbiotic cyanobacteria are found in other members of the Dinophysiales, e.g., Ornithocercus. Various dinophytes, e.g. Gymnodinium aeruginosum, use kleptochloroplasts from ingested cryptophytes transiently for photosynthesis. Original or secondarily acquired chloroplasts can only be used for phylogenetic considerations in exceptionally cases: it seems unlikely that the Prorocentrales have evolved from the Dinophysiales because all Prorocentrales possess original dinoflagellate chloroplasts, whereas no member of the Dinophysiales has such chloroplasts.     

Ligand-dependent kinase activity of MERTK drives efferocytosis in human iPSC-derived macrophages

Removal of apoptotic cells by phagocytes (also called efferocytosis) is a crucial process for tissue homeostasis. Professional phagocytes express a plethora of surface receptors enabling them to sense and engulf apoptotic cells, thus avoiding persistence of dead cells and cellular debris and their consequent effects. Dysregulation of efferocytosis is thought to lead to secondary necrosis and associated inflammation and immune activation. Efferocytosis in primarily murine macrophages and dendritic cells has been shown to require TAM RTKs, with MERTK and AXL being critical for clearance of apoptotic cells. The functional role of human orthologs, especially the exact contribution of each individual receptor is less well studied. Here we show that human macrophages differentiated in vitro from iPSC-derived precursor cells express both AXL and MERTK and engulf apoptotic cells. TAM RTK agonism by the natural ligand growth-arrest specific 6 (GAS6) significantly enhanced such efferocytosis. Using a newly-developed mouse model of kinase-dead MERTK, we demonstrate that MERTK kinase activity is essential for efferocytosis in peritoneal macrophages in vivo. Moreover, human iPSC-derived macrophages treated in vitro with blocking antibodies or small molecule inhibitors recapitulated this observation. Hence, our results highlight a conserved MERTK function between mice and humans, and the critical role of its kinase activity in homeostatic efferocytosis.Subject terms: Immune cell death, Peritoneal macrophages     

Comparative population genetics of seven notothenioid fish species reveals high levels of gene flow along ocean currents in the southern Scotia Arc, Antarctica

The Antarctic fish fauna is characterized by high endemism and low species diversity with one perciform suborder, the Notothenioidei, dominating the whole species assemblage on the shelves and slopes. Notothenioids diversified in situ through adaptive radiation and show a variety of life history strategies as adults ranging from benthic to pelagic modes. Their larval development is unusually long, lasting from a few months to more than a year, and generally includes a pelagic larval stage. Therefore, the advection of eggs and larvae with ocean currents is a key factor modulating population connectivity. Here, we compare the genetic population structures and gene flow of seven ecologically distinct notothenioid species of the southern Scotia Arc based on nuclear microsatellites and mitochondrial DNA sequences (D-loop/cytochrome b). The seven species belong to the families Nototheniidae (Gobionotothen gibberifrons, Lepidonotothen squamifrons, Trematomus eulepidotus, T. newnesi) and Channichthyidae (Chaenocephalus aceratus, Champsocephalus gunnari, Chionodraco rastrospinosus). Our results show low-population differentiation and high gene flow for all investigated species independent of their adult life history strategies. In addition, gene flow is primarily in congruence with the prevailing ocean current system, highlighting the role of larval dispersal in population structuring of notothenioids.     

Physical simulation of laryngeal disorders using a multiple-mass vocal fold model

This paper reports on the use of a high-dimensional discrete vocal fold model for the simulation of voice production under the presence of laryngeal disorders. Specifically, the effect of increases in mass and stiffness, both unilateral and bilateral, has been analysed independently for both magnitudes. The glottal flow waveform and the mass displacement have been studied and the obtained results are coherent with clinical observations that relate mass increments with lowered fundamental frequencies and mass and stiffness increments with reduced vibratory amplitudes of vocal folds. The reported results also indicate that asymmetries in the physical properties of vocal folds result in asymmetries in their vibratory patterns, including phase, amplitude and behaviour on collision. These are also correlated with voice perturbation measures such as jitter, shimmer and normalised noise energy.     

Climate-induced changes in bottom-up and top-down processes independently alter a marine ecosystem

Climate change has complex structural impacts on coastal ecosystems. Global warming is linked to a widespread decline in body size, whereas increased flood frequency can amplify nutrient enrichment through enhanced run-off. Altered population body-size structure represents a disruption in top-down control, whereas eutrophication embodies a change in bottom-up forcing. These processes are typically studied in isolation and little is known about their potential interactive effects. Here, we present the results of an in situ experiment examining the combined effects of top-down and bottom-up forces on the structure of a coastal marine community. Reduced average body mass of the top predator (the shore crab, Carcinus maenas) and nutrient enrichment combined additively to alter mean community body mass. Nutrient enrichment increased species richness and overall density of organisms. Reduced top-predator body mass increased community biomass. Additionally, we found evidence for an allometrically induced trophic cascade. Here, the reduction in top-predator body mass enabled greater biomass of intermediate fish predators within the mesocosms. This, in turn, suppressed key micrograzers, which led to an overall increase in microalgal biomass. This response highlights the possibility for climate-induced trophic cascades, driven by altered size structure of populations, rather than species extinction.     

Calcium‐dependent behavioural responses to acute copper exposure in Oncorhynchus mykiss

Using rainbow trout Oncorhynchus mykiss, the present study demonstrated that: (1) calcium (Ca) increased the range of copper (Cu) concentrations that O. mykiss avoided; (2) Ca conserved the maintenance of pre‐exposure swimming activity during inescapable acute (10 min) Cu exposure. Data showed that when presented with a choice of Cu‐contaminated water (ranging from 0 to 454 µg Cu l^?1) and uncontaminated water in a choice tank, O. mykiss acclimated and tested at low Ca concentration (3 mg Ca l^?1) avoided the 10 µg Cu l^?1 only. By contrast, O. mykiss acclimated and tested at high Ca concentration (158 mg Ca l^?1) avoided all the Cu concentrations ≥37 µg l^?1. The Cu avoidance was connected with increased spontaneous swimming speed in the Cu‐contaminated water. When subjected to inescapable Cu exposure (35 µg Cu l^?1), O. mykiss acclimated and tested at low Ca concentration reduced their spontaneous swimming speed, whereas no response was observed in O. mykiss acclimated and tested at high Ca concentration. Collectively, the data support the conclusion that in O. mykiss the behavioural responses to acute Cu exposure are Ca‐dependent.