Gene regulation by translational inhibition is determined by Dicer partnering proteins

MicroRNAs (miRNAs) are small regulatory RNAs produced by Dicer proteins that regulate gene expression in development and adaptive responses to the environment1,​2,​3,​4. In animals, the degree of base pairing between a miRNA and its target messenger RNA seems to determine whether the regulation occurs through cleavage or translation inhibition1. In contrast, the selection of regulatory mechanisms is independent of the degree of mismatch between a plant miRNA and its target transcript5. However, the components and mechanism(s) that determine whether a plant miRNA ultimately regulates its targets by guiding cleavage or translational inhibition are unknown6. Here we show that the form of regulatory action directed by a plant miRNA is determined by DRB2, a DICER-LIKE1 (DCL1) partnering protein. The dependence of DCL1 on DRB1 for miRNA biogenesis is well characterized7,​8,​9, but we show that it is only required for miRNA-guided transcript cleavage. We found that DRB2 determines miRNA-guided translational inhibition and represses DRB1 expression, thereby allowing the active selection of miRNA regulatory action. Furthermore, our results reveal that the core silencing proteins ARGONAUTE1 (AGO1) and SERRATE (SE) are highly regulated by miRNA-guided translational inhibition. DRB2 has been remarkably conserved throughout plant evolution, raising the possibility that translational repression is the ancient form of miRNA-directed gene regulation in plants, and that Dicer partnering proteins, such as human TRBP, might play a similar role in other eukaryotic systems.

Characterisation of lignins isolated from sugarcane bagasse pretreated with acidified ethylene glycol and ionic liquids

Sugarcane bagasse pretreatment processes using acidified aqueous ethylene glycol (EG) and ionic liquids (ILs) have been reported recently. In this study, recovery of lignins from these processes was conducted, as well as determination of their physico-chemical properties. The amount of lignins recovered from 1-butyl-3-methylimidazolium chloride ([bmim]Cl) with HCl as a catalyst and [bmim][CH3SO3] was ∼42%, and ∼35%–36% by EG with HCl or H2SO4 as a catalyst, respectively. The isolated lignins were characterised using wet chemistry, spectroscopy and thermogravimetry analysis (TGA), and the results compared to soda lignin from NaOH pretreatment of bagasse. The IL and EG lignins contained no or trace amounts of carbohydrates, slightly lower hydrogen content but slightly higher oxygen contents than soda lignin. The IL and EG lignins contained more C-3 and C-5 reactive sites for Mannich reaction and had more p-hydroxypheny propane unit structures than soda lignin. Two-dimensional heteronuclear single quantum coherence (2D HSQC) nuclear magnetic resonance (NMR) identified the major substructural units in the lignins, and allowed differences among them to be studied. As EG lignins were extracted in very reactive environment, intermediate enol ethers were formed and led to cleavage reactions which were not apparent in the other lignins. 31P NMR and infra-red spectroscopy results showed that IL and EG lignins had lower total hydroxyl content than soda lignin, probably indicating that a higher degree of self-polymerisation occurred during bagasse pretreatment, despite the use of lower temperature and shorter reaction time. On the basis of the salient features of these lignins, potential applications were proposed.

Copper nanoparticles on graphene support: An efficient photocatalyst for coupling of nitroaromatics in visible light

Copper is a low-cost plasmonic metal. Efficient photocatalysts of copper nanoparticles on graphene support are successfully developed for controllably catalyzing the coupling reactions of aromatic nitro compounds to the corresponding azoxy or azo compounds under visible-light irradiation. The coupling of nitrobenzene produces azoxybenzene with a yield of 90 % at 60 °C, but azobenzene with a yield of 96 % at 90 °C. When irradiated with natural sunlight (mean light intensity of 0.044 W cm−2) at about 35 °C, 70 % of the nitrobenzene is converted and 57 % of the product is azobenzene. The electrons of the copper nanoparticles gain the energy of the incident light through a localized surface plasmon resonance effect and photoexcitation of the bound electrons. The excited energetic electrons at the surface of the copper nanoparticles facilitate the cleavage of the NO bonds in the aromatic nitro compounds. Hence, the catalyzed coupling reaction can proceed under light irradiation and moderate conditions. This study provides a green photocatalytic route for the production of azo compounds and highlights a potential application for graphene.

A new regulatory variant in the interleukin-6 receptor gene associates with asthma risk

The main genetic determinant of soluble interleukin 6 receptor (sIL-6R) levels is the missense variant rs2228145 that maps to the cleavage site of IL-6R. For each Ala allele, sIL-6R serum levels increase by ∼20 ng ml -1 and asthma risk by 1.09-fold. However, this variant does not explain the total heritability for sIL-6R levels. Additional independent variants in IL6R may therefore contribute to variation in sIL-6R levels and influence asthma risk. We imputed 471 variants in IL6R and tested these for association with sIL-6R serum levels in 360 individuals. An intronic variant (rs12083537) was associated with sIL-6R levels independently of rs4129267 (P=0.0005), a proxy single-nucleotide polymorphism for rs2228145. A significant and consistent association for rs12083537 was observed in a replication panel of 354 individuals (P=0.033). Each rs12083537:A allele increased sIL-6R serum levels by 2.4 ng ml -1. Analysis of mRNA levels in two cohorts did not identify significant associations between rs12083537 and IL6R transcription levels. On the other hand, results from 16 705 asthmatics and 30 809 controls showed that the rs12083537:A allele increased asthma risk by 1.04-fold (P=0.0419). Genetic risk scores based on IL6R regulatory variants may prove useful in explaining variation in clinical response to tocilizumab, an anti-IL-6R monoclonal antibody.

Provinicializing curriculum? On the preparation of subjectivity for globality

The recent availability of international forums devoted expressly to discussing subfields of education such as curriculum studies has brought to visibility preexisting flashpoints that are not easily defused by strict adherence to definition of key terms. The difficulty of translating the term curriculum into “non”-Indo-European root languages, as well as among them, is a case in point and not just an issue of vocabulary. The difficulty of translation indexes a cleavage that is beyond-conceptual and exo-technical. Efforts to locate analogs or equivalents might suggest on the one hand, an ethnocentric preoccupation to extend the reach of a provincial concept (i.e., curriculum), while the effort to avoid or move to the side of such a preoccupation for translation might suggest structures of subjectivity that refuse co-option into foreign frames of reference. Both of these possibilities are, however, constitutive of and pointing to productive interstices from which to reengage and rephrase the weight given to subjectivity and language, to global/local divisions, and to the politics of traveling discourses in educational research.

Single layer bismuth iodide: Computational exploration of structural, electrical, mechanical and optical properties

Layered graphitic materials exhibit new intriguing electronic structure and the search for new types of two-dimensional (2D) monolayer is of importance for the fabrication of next generation miniature electronic and optoelectronic devices. By means of density functional theory (DFT) computations, we investigated in detail the structural, electronic, mechanical and optical properties of the single-layer bismuth iodide (BiI3) nanosheet. Monolayer BiI3 is dynamically stable as confirmed by the computed phonon spectrum. The cleavage energy (Ecl) and interlayer coupling strength of bulk BiI3 are comparable to the experimental values of graphite, which indicates that the exfoliation of BiI3 is highly feasible. The obtained stress-strain curve shows that the BiI3 nanosheet is a brittle material with a breaking strain of 13%. The BiI3 monolayer has an indirect band gap of 1.57 eV with spin orbit coupling (SOC), indicating its potential application for solar cells. Furthermore, the band gap of BiI3 monolayer can be modulated by biaxial strain. Most interestingly, interfacing electrically active graphene with monolayer BiI3 nanosheet leads to enhanced light absorption compared to that in pure monolayer BiI3 nanosheet, highlighting its great potential applications in photonics and photovoltaic solar cells.

Computational analyses of the catalytic and heparin-binding sites and their interactions with glycosaminoglycans in glycoside hydrolase family 79 endo-d-glucuronidase (heparanase)

Mammalian heparanase is an endo-β-glucuronidase associated with cell invasion in cancer metastasis, angiogenesis and inflammation. Heparanase cleaves heparan sulfate proteoglycans in the extracellular matrix and basement membrane, releasing heparin/heparan sulfate oligosaccharides of appreciable size. This in turn causes the release of growth factors, which accelerate tumor growth and metastasis. Heparanase has two glycosaminoglycan-binding domains; however, no three-dimensional structure information is available for human heparanase that can provide insights into how the two domains interact to degrade heparin fragments. We have constructed a new homology model of heparanase that takes into account the most recent structural and bioinformatics data available. Heparin analogs and glycosaminoglycan mimetics were computationally docked into the active site with energetically stable ring conformations and their interaction energies were compared. The resulting docked structures were used to propose a model for substrates and conformer selectivity based on the dimensions of the active site. The docking of substrates and inhibitors indicates the existence of a large binding site extending at least two saccharide units beyond the cleavage site (toward the nonreducing end) and at least three saccharides toward the reducing end (toward heparin-binding site 2). The docking of substrates suggests that heparanase recognizes the N-sulfated and O-sulfated glucosamines at subsite +1 and glucuronic acid at the cleavage site, whereas in the absence of 6-O-sulfation in glucosamine, glucuronic acid is docked at subsite +2. These findings will help us to focus on the rational design of heparanase-inhibiting molecules for anticancer drug development by targeting the two heparin/heparan sulfate recognition domains.

Effect of deletion of Ghrelin-O-Acyltransferase on the pulsatile release of growth hormone in mice

Ghrelin, a gut hormone originating from the post-translational cleavage of preproghrelin, is the endogenous ligand of growth hormone secretagogue receptor 1a (GHS-R1a). Within the growth hormone (GH) axis, the biological activity of ghrelin requires octanoylation by ghrelin-O-acyltransferase (GOAT), conferring selective binding to the GHS-R1a receptor via acylated ghrelin. Complete loss of preproghrelin-derived signalling (through deletion of the Ghrl gene) contributes to a decline in peak GH release; however, the selective contribution of endogenous acyl-ghrelin to pulsatile GH release remains to be established. We assessed the pulsatile release of GH in ad lib. fed male germline goat−/− mice, extending measures to include mRNA for key hypothalamic regulators of GH release, and peripheral factors that are modulated relative to GH release. The amount of GH released was reduced in young goat−/− mice compared to age-matched wild-type mice, whereas pulse frequency and irregularity increased. Altered GH release did not coincide with alterations in hypothalamic Ghrh, Srif, Npy or Ghsr mRNA expression, or pituitary GH content, suggesting that loss of Goat does not compromise canonical mechanisms that contribute to pituitary GH production and release. Although loss of Goat resulted in an irregular pattern of GH release (characterised by an increase in the number of GH pulses observed during extended secretory events), this did not contribute to a change in the expression of sexually dimorphic GH-dependent liver genes. Of interest, circulating levels of insulin-like growth factor (IGF)-1 were elevated in goat−/− mice. This rise in circulating levels of IGF-1 was correlated with an increase in GH pulse frequency, suggesting that sustained or increased IGF-1 release in goat−/− mice may occur in response to altered GH release patterning. Our observations demonstrate that germline loss of Goat alters GH release and patterning. Although the biological relevance of altered GH secretory patterning remains unclear, we propose that this may contribute to sustained IGF-1 release and growth in goat−/− mice.

Predicting single-layer technetium dichalcogenides (TcX2, X = S, Se) with promising applications in photovoltaics and photocatalysis

One of the least known compounds among transition metal dichalcogenides (TMDCs) is the layered triclinic technetium dichalcogenides (TcX2, X = S, Se). In this work, we systematically study the structural, mechanical, electronic, and optical properties of TcS2 and TcSe2 monolayers based on density functional theory (DFT). We find that TcS2 and TcSe2 can be easily exfoliated in a monolayer form because their formation and cleavage energy are analogous to those of other experimentally realized TMDCs monolayer. By using a hybrid DFT functional, the TcS2 and TcSe2 monolayers are calculated to be indirect semiconductors with band gaps of 1.91 and 1.69 eV, respectively. However, bilayer TcS2 exhibits direct-bandgap character, and both TcS2 and TcSe2 monolayers can be tuned from semiconductor to metal under effective tensile/compressive strains. Calculations of visible light absorption indicate that 2D TcS2 and TcSe2 generally possess better capability of harvesting sunlight compared to single-layer MoS2 and ReSe2, implying their potential as excellent light-absorbers. Most interestingly, we have discovered that the TcSe2 monolayer is an excellent photocatalyst for splitting water into hydrogen due to the perfect fit of band edge positions with respect to the water reduction and oxidation potentials. Our predictions expand the two-dimensional (2D) family of TMDCs, and the remarkable electronic/optical properties of monolayer TcS2 and TcSe2 will place them among the most promising 2D TMDCs for renewable energy application in the future.

The quest for golden bananas: Investigating carotenoid regulation in a Fe’i group Musa cultivar

The regulation of carotenoid biosynthesis in a high-carotenoid-accumulating Fe’i group Musa cultivar, “Asupina”, has been examined and compared to that of a low-carotenoid-accumulating cultivar, “Cavendish”, to understand the molecular basis underlying carotenogenesis during banana fruit development. Comparisons in the accumulation of carotenoid species, expression of isoprenoid genes, and product sequestration are reported. Key differences between the cultivars include greater carotenoid cleavage dioxygenase 4 (CCD4) expression in “Cavendish” and the conversion of amyloplasts to chromoplasts during fruit ripening in “Asupina”. Chromoplast development coincided with a reduction in dry matter content and fruit firmness. Chromoplasts were not observed in “Cavendish” fruits. Such information should provide important insights for future developments in the biofortification and breeding of banana.