De novo variants in the RNU4-2 snRNA cause a frequent neurodevelopmental syndrome

Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes1. Large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here, we identify the non-coding RNA RNU4-2 as a syndromic NDD gene. RNU4-2 encodes the U4 small nuclear RNA (snRNA), which is a critical component of the U4/U6.U5 tri-snRNP complex of the major spliceosome2. We identify an 18 bp region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and Stem III) that is severely depleted of variation in the general population, but in which we identify heterozygous variants in 115 individuals with NDD. Most individuals (77.4%) have the same highly recurrent single base insertion (n.64_65insT). In 54 individuals where it could be determined, the de novo variants were all on the maternal allele. We demonstrate that RNU4-2 is highly expressed in the developing human brain, in contrast to RNU4-1 and other U4 homologs. Using RNA-sequencing, we show how 5’ splice site usage is systematically disrupted in individuals with RNU4-2 variants, consistent with the known role of this region during spliceosome activation. Finally, we estimate that variants in this 18 bp region explain 0.4% of individuals with NDD. This work underscores the importance of non-coding genes in rare disorders and will provide a diagnosis to thousands of individuals with NDD worldwide

Magnetic Fe@Y Composites as Efficient Recoverable Catalysts for the Valorization of the Recalcitrant Marine Sulfated Polysaccharide Ulvan

Magnetic Fe@Y composites (carbon-coated magnetic iron nanoparticles incorporated in zeolite Y) with 5-8 wt % Fe were synthesized and characterized. Overall acidity of the samples ranged between 2.0 and 2.47 mmol/g and is mostly attributed to Lewis acid sites. The obtained materials were proven to catalyze the hydrolysis of the marine sulfated polysaccharide ulvan with high conversion rates. The distribution of the reaction products depended on the reaction conditions and the concentration of ulvan. The catalytic property-catalytic performance correlations clearly showed that the acid zeolite Y is the active phase for the hydrolysis of ulvan, while the iron nanoparticles enable the catalyst separation in a magnetic field. Under oxygen pressure, the selectivity was completely changed to favor succinic acid production. All Fe@Y composites were recycled 10 times with no change in their catalytic performance after recovery via a simple magnetic separation and washing with water. Copyright © 2019 American Chemical Society

Efficient and green access to functionalized and highly constrained heteropolycyclic derivatives via a microwave accelerated Diels-Alder cycloaddition and heterogeneous hydrogenation sequence

International audienc

Efficient and Green Access to Functionalized and Highly Constrained Heteropolycyclic Derivatives via a Microwave-Accelerated Diels-Alder Cycloaddition and Heterogeneous Hydrogenation Sequence

International audienc

Nitrogen-doped graphene as metal free basic catalyst for coupling reactions

N-doped defective graphene [(N)G] obtained by pyrolysis at 900 °C of chitosan contains about 3.7% of residual N atoms, distributed as pyridinic, pyrrolic and graphitic N atoms. It has been found that (N)G acts as basic catalyst promoting two classical C[sbnd]C bond forming nucleophilic additions in organic chemistry, such as the Michael and the Henry additions. Computational calculations at DFT level of models corresponding to the various N atoms leads to the conclusion that N atoms are more stable at the periphery of the graphene sheets and that H adsorption on these sites is a suitable descriptor to correlate with the catalytic activity of the various sites. According to these calculations the most active sites are pyridinic N atoms at zig-zag edges of the sheets. In addition, N as dopant changes the reactivity of the neighbour C atoms. Water was found a suitable solvent to achieve high conversions in both reactions. In this solvent the initial distribution of N atoms is affected due to the easy protonation of the N to N sites. As an effect, C edge sites adjacent at N with an appropriate reactivity towards the α-C-H bond breaking are formed. The present results show the general activity of N-doped graphene as base catalysts and illustrate the potential of carbocatalysis to promote reactions of general interest in organic synthesis

Catalytic transformation of the marine polysaccharide ulvan into rare sugars, tartaric and succinic acids

The green macroalga Ulva rigida represents a promising feedstock for biorefinary due to its fast growth and cosmopolitan distribution. The main component of the cell walls of U. rigida is a sulfated glucuronorhamnan polysaccharide known as ulvan. Herein it was found that due to the high (hydrogen)sulfate group content of ulvan, hydrothermal autohydrolysis at 130 °C renders a high percentage of rhamnose (78–79 % recovery from the initial content in the raw material), a rare sugar of high added value. In addition, acid catalysis by a triflate-based graphene oxide under oxygen-free conditions at 180 °C affords moderate amounts of tartaric acid (24–26 %). The same triflate-based graphene oxide catalyst under oxygen pressure yields remarkably high percentages of succinic acid (65 %). The catalyst preserves its activity for at least five consecutive reuses. © 2020 Elsevier B.V

Catalytic transformation of the marine polysaccharide ulvan into rare sugars, tartaric and succinic acids

The green macroalga Ulva rigida represents a promising feedstock for biorefinary due to its fast growth and cosmopolitan distribution. The main component of the cell walls of U. rigida is a sulfated glucuronorhamnan polysaccharide known as ulvan. Herein it was found that due to the high (hydrogen)sulfate group content of ulvan, hydrothermal autohydrolysis at 130 °C renders a high percentage of rhamnose (78–79 % recovery from the initial content in the raw material), a rare sugar of high added value. In addition, acid catalysis by a triflate-based graphene oxide under oxygen-free conditions at 180 °C affords moderate amounts of tartaric acid (24–26 %). The same triflate-based graphene oxide catalyst under oxygen pressure yields remarkably high percentages of succinic acid (65 %). The catalyst preserves its activity for at least five consecutive reuses.Financial support by the Spanish Ministry of Economy and Competitiveness (Severo Ochoa SEV2016-0683, RTI2018-890237-CO2-R1) and Generalitat Valenciana (Prometeo 2017−083) is gratefully acknowledged. Vasile I. Parvulescu kindly acknowledges UEFISCDI for financial support (project PN-III-P4-ID-PCE-2016-0146, Nr. 121/2017)

Estimulantes alimentares para larvas de pacu Feeding stimulants for pacu lavae

Este estudo foi realizado com o objetivo de investigar o efeito estimulante de cinco aminoácidos (alanina, arginina, glicina, histidina e lisina) da betaína e de suas misturas sobre a taxa de ingestão de dieta microencapsulada durante o desenvolvimento larval de pacu Piaractus mesopotamicus. Os resultados da análise estatística comprovaram a existência de efeito significativo, tanto da idade das larvas como dos aminoácidos, sobre a taxa de ingestão. No entanto, não houve significância estatística para a interação dos dois fatores. A glicina, a lisina e a beta��na foram considerados bons estimuladores do comportamento alimentar de larvas de pacu.<br>The present study aimed to investigate the stimulant effect of five amino acids (alanine, arginine, glycine, histidine and lysine) from betaine and their mixtures on the ingestion rates of formulated diet during the larval development of pacu Piaractus mesopotamicus. The statistical results showed significant effect of age and treatment. However, no significant effect was observed for the interaction of both factors. Glycine, lysine and betaine are considered good stimulants of the pacu feeding behavior