Developmental regulation of canonical and small ORF translation from mRNAs

Background: Ribosomal profiling has revealed the translation of thousands of sequences outside annotated protein-coding genes, including small open reading frames of less than 100 codons, and the translational regulation of many genes. Here we present an improved version of Poly-Ribo-Seq and apply it to Drosophila melanogaster embryos to extend the catalog of in vivo translated small ORFs, and to reveal the translational regulation of both small and canonical ORFs from mRNAs across embryogenesis. Results: We obtain highly correlated samples across five embryonic stages, with nearly 500 million putative ribosomal footprints mapped to mRNAs, and compare them to existing Ribo-Seq and proteomic data. Our analysis reveals, for the first time in Drosophila, footprints mapping to codons in a phased pattern, the hallmark of productive translation. We propose a simple binomial probability metric to ascertain translation probability. Our results also reveal reproducible ribosomal binding apparently not resulting in productive translation. This non-productive ribosomal binding seems to be especially prevalent amongst upstream short ORFs located in the 5′ mRNA leaders, and amongst canonical ORFs during the activation of the zygotic translatome at the maternal-to zygotic transition. Conclusions: We suggest that this non-productive ribosomal binding might be due to cis-regulatory ribosomal binding and to defective ribosomal scanning of ORFs outside periods of productive translation. Our results are compatible with the main function of upstream short ORFs being to buffer the translation of canonical canonical ORFs; and show that, in general, small ORFs in mRNAs display markers compatible with an evolutionary transitory state towards full coding function

Alveolar ridge preservation reduces the need for ancillary bone augmentation in the context of implant therapy.

BACKGROUND There is limited information on the need for bone augmentation in the context of delayed implant placement whether alveolar ridge preservation (ARP) is previously performed or not. The primary aim of this retrospective cohort study was to evaluate the efficacy of ARP therapy after tooth extraction compared with unassisted socket healing (USH) in reducing the need for ancillary bone augmentation before or at the time of implant placement. METHODS Adult subjects that underwent non-molar single tooth extraction with or without simultaneous ARP therapy were included in this study. Cone beam computed tomography scans obtained before tooth extraction and after a variable healing period were used to record the baseline facial bone thickness and to virtually plan implant placement according to a standard method. A logistic regression model was used to evaluate the effect of facial alveolar bone thickness upon tooth extraction and baseline therapy (USH or ARP) on the need for additional bone augmentation, adjusting for several covariates (i.e., age, sex, baseline KMW, and tooth type). RESULTS One hundred and forty subjects that were equally distributed between both baseline therapy groups constituted the study population. Implant placement was deemed virtually feasible in all study sites. Simultaneous bone augmentation was considered necessary in 60% and 11.4% of the sites in the USH and ARP group, respectively. Most of these sites (64.2% in the USH group and 87.5% in the ARP group) exhibited a thin facial bone phenotype (<1 mm) at baseline. Logistic regression revealed that the odds of not needing ancillary bone augmentation were 17.8 times higher in sites that received ARP therapy. Furthermore, the need for additional bone augmentation was reduced 7.7 times for every 1 mm increase in facial bone thickness, regardless of baseline therapy. CONCLUSIONS Based on a digital analysis, ARP therapy, compared with USH, and thick facial alveolar bone largely reduce the need for ancillary bone augmentation at the time of implant placement in non-molar sites

Finding smORFs: getting closer

Millions of small open reading frames exist in eukaryotes. We do not know how many, or which are translated, but bioinformatics is getting us closer to the answer. See related Research article: http://www.genomebiology.com/2015/16/1/179

The actin-binding protein profilin 2 is a novel regulator of iron homeostasis

Cellular iron homeostasis is controlled by the iron regulatory proteins (IRPs) 1 and 2 that bind cis-regulatory iron-responsive elements (IRE) on target messenger RNAs (mRNA). We identified profilin 2 (Pfn2) mRNA, which encodes an actin-binding protein involved in endocytosis and neurotransmitter release, as a novel IRP-interacting transcript, and studied its role in iron metabolism. A combination of electrophoretic mobility shift assay experiments and bioinformatic analyses led to the identification of an atypical and conserved IRE in the 39 untranslated region of Pfn2 mRNA. Pfn2 mRNA levels were significantly reduced in duodenal samples from mice with intestinal IRP ablation, suggesting that IRPs exert a positive effect on Pfn2 mRNA expression in vivo. Overexpression of Pfn2 in HeLa and Hepa1-6 cells reduced their metabolically active iron pool. Importantly, Pfn2-deficient mice showed iron accumulation in discrete areas of the brain (olfactory bulb, hippocampus, and midbrain) and reduction of the hepatic iron store without anemia. Despite low liver iron levels, hepatic hepcidin expression remained high, likely because of compensatory activation of hepcidin by mild inflammation. Splenic ferroportin was increased probably to sustain hematopoiesis. Overall, our results indicate that Pfn2 expression is controlled by the IRPs in vivo and that Pfn2 contributes to maintaining iron homeostasis in cell lines and mice

Unquenched flavor and tropical geometry in strongly coupled Chern-Simons-matter theories

We study various aspects of the matrix models calculating free energies and Wilson loop observables in supersymmetric Chern-Simons-matter theories on the three-sphere. We first develop techniques to extract strong coupling results directly from the spectral curve describing the large N master field. We show that the strong coupling limit of the gauge theory corresponds to the so-called tropical limit of the spectral curve. In this limit, the curve degenerates to a planar graph, and matrix model calculations reduce to elementary line integrals along the graph. As an important physical application of these tropical techniques, we study N=3 theories with fundamental matter, both in the quenched and in the unquenched regimes. We calculate the exact spectral curve in the Veneziano limit, and we evaluate the planar free energy and Wilson loop observables at strong coupling by using tropical geometry. The results are in agreement with the predictions of the AdS duals involving tri-Sasakian manifoldsComment: 32 pages, 7 figures. v2: small corrections, added an Appendix on the relation with the approach of 1011.5487. v3: further corrections and clarifications, final version to appear in JHE

Dioxin Toxicity In Vivo Results from an Increase in the Dioxin-Independent Transcriptional Activity of the Aryl Hydrocarbon Receptor

The Aryl hydrocarbon receptor (Ahr) is the nuclear receptor mediating the toxicity of dioxins -widespread and persistent pollutants whose toxic effects include tumor promotion, teratogenesis, wasting syndrome and chloracne. Elimination of Ahr in mice eliminates dioxin toxicity but also produces adverse effects, some seemingly unrelated to dioxin. Thus the relationship between the toxic and dioxin-independent functions of Ahr is not clear, which hampers understanding and treatment of dioxin toxicity. Here we develop a Drosophila model to show that dioxin actually increases the in vivo dioxin-independent activity of Ahr. This hyperactivation resembles the effects caused by an increase in the amount of its dimerisation partner Ahr nuclear translocator (Arnt) and entails an increased transcriptional potency of Ahr, in addition to the previously described effect on nuclear translocation. Thus the two apparently different functions of Ahr, dioxin-mediated and dioxin-independent, are in fact two different levels (hyperactivated and basal, respectively) of a single function

L'Energia en context

Presentem el material didàctic L'energia en context, un projecte elaborat i experimentat pel grup de treball Scientia Omnibus, un equip de professors/es de secundària de diverses especialitats de ciències. Consta de 3 unitats didàctiques amb un enfoc CTS (ciència - tecnologia - societat) adreçades a alumnat del segon cicle d'ESO que tracten els continguts curriculars relacionats amb l'energia. L'elecció d'aquest tema com a eix vertebrador de tot el projecte s'ha realitzat per la rellevància social i personal que té a la nostra societat. Les estratègies didàctiques clau del projecte són la contextualització de la ciència escolar i el treball cooperatiu. També fomenta la interacció social i l'autonomia d'aprenentatge de l'alumnat, utilitzant diversos tipus d'activitats (estudis de casos, recerques, problemes, etc.)

Representative Set of Objects in Rough Sets Based on Galois Connections

This paper introduces a novel definition, called representative set of objects of a decision class, in the framework of decision systems based on rough sets. The idea behind such a notion is to consider subsets of objects that characterize the different classes given by a decision system. Besides the formal definition of representative set of objects of a decision class, we present different mathematical properties of such sets and a relationship with classification tasks based on rough sets. © 2020, Springer Nature Switzerland AG