MicroRNAs Act as Cofactors in Bicoid-Mediated Translational Repression

SummaryNoncoding RNAs have recently emerged as important regulators of mRNA translation and turnover [1, 2]. Nevertheless, we largely ignore how their function integrates with protein-mediated translational regulation. We focus on Bicoid, a key patterning molecule in Drosophila, which inhibits the translation of caudal in the anterior part of the embryo [3, 4]. Previous work showed that Bicoid recruits the cap-binding protein d4EHP on the caudal mRNA to repress translation [5]. Here we show that miR-2 family microRNAs are essential cofactors in the repression of caudal. Using an in vivo sensor, we demonstrate that Bicoid acts through a 63 nt response element in the caudal 3′ UTR that includes a single miR-2 target site. Mutating that site abolishes Bicoid-mediated repression, and this effect can be partly reversed by expressing a microRNA with compensatory changes that restore binding to the mutated target. Four predicted Bicoid splice isoforms are capable of caudal repression, including two that lack the d4EHP interaction domain; all four isoforms require the microRNA target for repression. The synergy between Bicoid and microRNAs appears to have evolved recently in the context of the drosophilid caudal BRE. The discovery that microRNAs play an essential role in Bicoid-mediated translational repression opens up new perspectives on Bicoid’s function and evolution

Evolutionary conservation of the eumetazoan gene regulatory landscape

Despite considerable differences in morphology and complexity of body plans among animals, a great part of the gene set is shared among Bilateria and their basally branching sister group, the Cnidaria. This suggests that the common ancestor of eumetazoans already had a highly complex gene repertoire. At present it is therefore unclear how morphological diversification is encoded in the genome. Here we address the possibility that differences in gene regulation could contribute to the large morphological divergence between cnidarians and bilaterians. To this end, we generated the first genome-wide map of gene regulatory elements in a nonbilaterian animal, the sea anemone Nematostella vectensis. Using chromatin immunoprecipitation followed by deep sequencing of five chromatin modifications and a transcriptional cofactor, we identified over 5000 enhancers in the Nematostella genome and could validate 75% of the tested enhancers in vivo. We found that in Nematostella, but not in yeast, enhancers are characterized by the same combination of histone modifications as in bilaterians, and these enhancers preferentially target developmental regulatory genes. Surprisingly, the distribution and abundance of gene regulatory elements relative to these genes are shared between Nematostella and bilaterian model organisms. Our results suggest that complex gene regulation originated at least 600 million yr ago, predating the common ancestor of eumetazoans

Detection of Influenza D-Specific Antibodies in Bulk Tank Milk from Swedish Dairy Farms

Influenza D virus (IDV) has been detected in bovine respiratory disease (BRD) outbreaks, and experimental studies demonstrated this virus's capacity to cause lesions in the respiratory tract. In addition, IDV-specific antibodies were detected in human sera, which indicated that this virus plays a potential zoonotic role. The present study aimed to extend our knowledge about the epidemiologic situation of IDV in Swedish dairy farms, using bulk tank milk (BTM) samples for the detection of IDV antibodies. A total of 461 and 338 BTM samples collected during 2019 and 2020, respectively, were analyzed with an in-house indirect ELISA. In total, 147 (32%) and 135 (40%) samples were IDV-antibody-positive in 2019 and 2020, respectively. Overall, 2/125 (2%), 11/157 (7%) and 269/517 (52%) of the samples were IDV-antibody-positive in the northern, middle and southern regions of Sweden. The highest proportion of positive samples was repeatedly detected in the south, in the county of Halland, which is one of the counties with the highest cattle density in the country. In order to understand the epidemiology of IDV, further research in different cattle populations and in humans is required

A dedicated flavin-dependent monooxygenase catalyzes the hydroxylation of demethoxyubiquinone into ubiquinone (coenzyme Q) in \u3ci\u3eArabidopsis\u3c/i\u3e

Ubiquinone (Coenzyme Q) is a vital respiratory cofactor and liposoluble antioxidant. In plants, it is not known how the C-6 hydroxylation of demethoxyubiquinone, the penultimate step in ubiquinone biosynthesis, is catalyzed. The combination of cross-species gene network modeling along with mining of embryo-defective mutant databases of Arabidopsis thaliana identified the embryo lethal locus EMB2421 (At1g24340) as a top candidate for the missing plant demethoxyubiquinone hydroxylase. In marked contrast with prototypical eukaryotic demethoxyubiquinone hydroxylases, the catalytic mechanism of which depends on a carboxylatebridged di-iron domain, At1g24340 is homologous to FADdependent oxidoreductases that instead use NAD(P)H as an electron donor. Complementation assays in Saccharomyces cerevisiae and Escherichia coli demonstrated that At1g24340 encodes a functional demethoxyubiquinone hydroxylase and that the enzyme displays strict specificity for the C-6 position of the benzoquinone ring. Laser-scanning confocal microscopy also showed that GFP-tagged At1g24340 is targeted to mitochondria. Silencing of At1g24340 resulted in 40 to 74% decrease in ubiquinone content and de novo ubiquinone biosynthesis. Consistent with the role of At1g24340 as a benzenoid ring modification enzyme, this metabolic blockage could not be bypassed by supplementation with 4-hydroxybenzoate, the immediate precursor of ubiquinone’s ring. Unlike in yeast, in Arabidopsis overexpression of demethoxyubiquinone hydroxylase did not boost ubiquinone content. Phylogenetic reconstructions indicated that plant demethoxyubiquinone hydroxylase is most closely related to prokaryotic monooxygenases that act on halogenated aromatics and likely descends from an event of ho

Murine type VII collagen distorts outcome in human skin graft mouse model for dystrophic epidermolysis bullosa

Human skin graft mouse models are widely used to investigate and develop therapeutic strategies for the severe generalized form of recessive dystrophic epidermolysis bullosa (RDEB), which is caused by bi-allelic null mutations in COL7A1 and the complete absence of type VII collagen (C7). Most therapeutic approaches are focused on reintroducing C7. Therefore, C7 and anchoring fibrils are widely used as readouts in therapeutic research with skin graft models. In this study, we investigated the expression pattern of human and murine C7 in a grafting model, in which human skin is reconstituted out of in vitro cultured keratinocytes and fibroblasts. The model revealed that murine C7 was deposited in both human healthy control and RDEB skin grafts. Moreover, we found that murine C7 is able to form anchoring fibrils in human grafts. Therefore, we advocate the use of human-specific antibodies when assessing the reintroduction of C7 using RDEB skin graft mouse models. This article is protected by copyright. All rights reserved

The embodied becoming of autism and childhood: a storytelling methodology

In this article I explore a methodology of storytelling as a means of bringing together research around autism and childhood in a new way, as a site of the embodied becoming of autism and childhood. Through reflection on an ethnographic story of embodiment, the body is explored as a site of knowledge production that contests its dominantly storied subjectivation as a ‘disordered’ child. Storytelling is used to experiment with a line of flight from the autistic-child-research assemblage into new spaces of potential and possibility where the becomings of bodies within the collision of autism and childhood can be celebrated

Honey bee colony winter loss rates for 35 countries participating in the COLOSS survey for winter 2018–2019, and the effects of a new queen on the risk of colony winter loss

peer-reviewedThis article presents managed honey bee colony loss rates over winter 2018/19 resulting from using the standardised COLOSS questionnaire in 35 countries (31 in Europe). In total, 28,629 beekeepers supplying valid loss data wintered 738,233 colonies, and reported 29,912 (4.1%, 95% confidence interval (CI) 4.0–4.1%) colonies with unsolvable queen problems 79,146 (10.7%, 95% CI 10.5–10.9%) dead colonies after winter and 13,895 colonies (1.9%, 95% CI 1.8–2.0%) lost through natural disaster. This gave an overall colony winter loss rate of 16.7% (95% CI 16.4–16.9%), varying greatly between countries, from 5.8% to 32. 0%. We modelled the risk of loss as a dead/empty colony or from unresolvable queen problems and found that, overall, larger beekeeping operations with more than 150 colonies experienced significantly lower losses (p<0.001), consistent with earlier studies. Additionally, beekeepers included in this survey who did not migrate their colonies at least once in 2018 had significantly lower losses than those migrating (p<0.001). The percentage of new queens from 2018 in wintered colonies was also examined as a potential risk factor. The percentage of colonies going into winter with a new queen was estimated as 55.0% over all countries. Higher percentages of young queens corresponded to lower overall losses (excluding losses from natural disaster), but also lower losses from unresolvable queen problems, and lower losses from winter mortality (p<0.001). Detailed results for each country and overall are given in a table, and a map shows relative risks of winter loss at regional level