TrxT and dhd are dispensable for Drosophila brain development but essential for l(3)mbt brain tumour growth.

Expression of the Drosophila cancer-germline (CG), X-linked, head-to-head gene pair TrxT and dhd is normally germline-specific but becomes upregulated in brain tumours caused by mutation in l(3)mbt. Here, we show that TrxT and dhd play a major synergistic role in the emergence of l(3)mbt tumour-linked transcriptomic signatures and tumour development, which is remarkable, taking into account that these two genes are never expressed together under normal conditions. We also show that TrxT, but not dhd, is crucial for the growth of l(3)mbt allografts, hence suggesting that the initial stages of tumour development and long-term tumour growth may depend on different molecular pathways. In humans, head-to-head inverted gene pairs are abundant among CG genes that map to the X chromosome. Our results identify a first example of an X-linked, head-to-head CG gene pair in Drosophila, underpinning the potential of such CG genes, dispensable for normal development and homoeostasis of somatic tissue, as targets to curtail malignant growth with minimal impact on overall health.

Illuminati: a form of gene expression plasticity in Drosophila neural stem cells.

While testing for genome instability in Drosophila as reported by unscheduled upregulation of UAS-GFP in cells that co-express GAL80 and GAL4, we noticed that, as expected, background levels were low in most developing tissues. However, GFP-positive clones were frequent in the larval brain. Most of these clones originated from central brain neural stem cells. Using imaging-based approaches and genome sequencing, we show that these unscheduled clones do not result from chromosome loss or mutations in GAL80. We have named this phenomenon 'Illuminati'. Illuminati is strongly enhanced in brat tumors and is also sensitive to environmental conditions such as food content and temperature. Illuminati is suppressed by Su(var)2-10, but it is not significantly affected by several modifiers of position effect variegation or Gal4::UAS variegation. We conclude that Illuminati identifies a previously unknown type of functional instability that may have important implications in development and disease.

Dielectric Analysis of Blended Polysulfone/Polyethylenimine Membrane Contactors for CO2 Capture.

Polysulfone membranes, used as contactors for CO2 capture, are blended with two different hyperbranched polyethyleneimines modified with benzoyl chloride (Additive 1) and phenyl isocyanate (Additive 2) in different percentages. Fourier-transformed infrared spectra evidence the presence of urea and amide groups, whereas the field emission scanning electron microscopy images show differences in the microstructure of the blended membranes. Dielectric spectra determine the motions of the side and backbone chains, which can facilitate the diffusion of CO2 . The spectra consist of six dielectric processes; three of them are due to the polysulfone (γPSf , ßPSf , and αPSf ), whereas the rest are characteristic of the additive (γHPEI , ßHPEI , and αHPEI ). The benzoyl chloride and phenyl isocyanate functional groups introduce variations in molecular mobility and modify the relaxations associated with the hyperbranched polyethyleneimine (HPEI). The additives also increase the conductivity of the blended membranes, which can compromise the performance of the membranes, specifically in the case of Additive 1. Ion hopping is found to be the prevailing charge transport mechanism while both relaxations, αHPEI and αPSf , are actives. These results, together with the final morphology of the membranes, may explain the greater absorption capacity of the membranes prepared with the hyperbranched polyethyleneimine modified with Additive 2.

Sensitivity of Mass Geometry Parameters on E-Scooter Comfort: Design Guide.

E-scooter vibrations are a problem recently studied. Theoretical models based on dynamic simulations and also real measurements have confirmed the high impact of e-scooter vibrations on driver comfort and health. Some authors recommend improving e-scooter damping systems, including tyres. However, it has not been suggested nor has any research been published studying how to improve e-scooter frame design for reducing driver vibrations and improving comfort. In this paper, we have modelled a real e-scooter to have a reference. Then, we have developed a multibody dynamic model for running dynamic simulations studying the influence of mass geometry parameters of the e-scooter frame (mass, centre of gravity and inertia moment). Acceleration results have been analysed based on the UNE-2631 standard for obtaining comfort values. Based on results, a qualitative e-scooter frame design guide for mitigating vibrations and increasing the comfort of e-scooter driver has been developed. Some application cases have been running on the multibody dynamic simulation model, finding improvements of comfort levels higher than 9% in comparison with the e-scooter reference model. The dynamic model has been qualitatively validated from real measurements. In addition, a basic sensor proposal and comfort colour scale is proposed for giving feedback to e-scooter drivers.

Readily regenerable amine-free CO2 sorbent based on a solid-supported carboxylate ionic liquid.

Accumulation of anthropogenic CO2 is undoubtedly the major cause of global warming. In addition to reducing emissions, minimising the threatening effects of climate change in the near future might also require the capture of enormous amounts of CO2 from point sources or from the atmosphere. In this regard, the development of novel affordable and energetically attainable capture technologies is greatly needed. In this work, we report rapid and greatly facilitated CO2 desorption for amine-free carboxylate ionic liquid hydrates as compared to a benchmark amine-based sorbent. Complete regeneration was achieved at moderate temperature (60 °C) over short capture-release cycles using model flue gas on a silica-supported tetrabutylphosphonium acetate ionic liquid hydrate (IL/SiO2), whereas the polyethyleneimine counterpart (PEI/SiO2) only recovered half its capacity after the first cycle in a rather sluggish release process under the same conditions. The IL/SiO2 sorbent achieved a slightly superior working CO2 capacity than PEI/SiO2. The easier regeneration of carboxylate ionic liquid hydrates, which behave as chemical CO2 sorbents leading to bicarbonate in a 1:1 stoichiometry, is due to their relatively low sorption enthalpies (≈40 kJ mol-1). The faster and more efficient desorption from IL/SiO2 fits a first-order kinetic model (k = 0.73 min-1), whereas a more complex process was observed for PEI/SiO2 (pseudo-first order initially, k = 0.11 min-1, pseudo-zero order at later stages). The remarkably low regeneration temperature, the absence of amines and the non-volatility of the IL sorbent are favourable assets to minimise gaseous stream contamination. Importantly, regeneration heats -a crucial parameter for practical application- are advantageous for IL/SiO2 (4.3 kJ g (CO2)-1) vs. PEI/SiO2, and fall within the range of typical amine sorbents indicating a remarkable performance at this proof-of-concept stage. Further structural design will enhance the viability of amine-free ionic liquid hydrates for carbon capture technologies.

A 3D Peptide/[60]Fullerene Hybrid for Multivalent Recognition.

Fully substituted peptide/[60]fullerene hexakis-adducts offer an excellent opportunity for multivalent protein recognition. In contrast to monofunctionalized fullerene hybrids, peptide/[60]fullerene hexakis-adducts display multiple copies of a peptide in close spatial proximity and in the three dimensions of space. High affinity peptide binders for almost any target can be currently identified by in vitro evolution techniques, often providing synthetically simpler alternatives to natural ligands. However, despite the potential of peptide/[60]fullerene hexakis-adducts, these promising conjugates have not been reported to date. Here we present a synthetic strategy for the construction of 3D multivalent hybrids that are able to bind with high affinity the E-selectin. The here synthesized fully substituted peptide/[60]fullerene hybrids and their multivalent recognition of natural receptors constitute a proof of principle for their future application as functional biocompatible materials.

AhaP, A Quorum Quenching Acylase from Psychrobacter sp. M9-54-1 That Attenuates Pseudomonas aeruginosa and Vibrio coralliilyticus Virulence.

Although Psychrobacter strain M9-54-1 had been previously isolated from the microbiota of holothurians and shown to degrade quorum sensing (QS) signal molecules C6 and C10-homoserine lactone (HSL), little was known about the gene responsible for this activity. In this study, we determined the whole genome sequence of this strain and found that the full 16S rRNA sequence shares 99.78-99.66% identity with Psychrobacter pulmonis CECT 5989T and P. faecalis ISO-46T. M9-54-1, evaluated using the agar well diffusion assay method, showed high quorum quenching (QQ) activity against a wide range of synthetic N-acylhomoserine lactone (AHLs) at 4, 15, and 28 °C. High-performance liquid chromatography-mass-spectrometry (HPLC-MS) confirmed that QQ activity was due to an AHL-acylase. The gene encoding for QQ activity in strain M9-54-1 was identified from its genome sequence whose gene product was named AhaP. Purified AhaP degraded substituted and unsubstituted AHLs from C4- to C14-HSL. Furthermore, heterologous expression of ahaP in the opportunistic pathogen Pseudomonas aeruginosa PAO1 reduced the expression of the QS-controlled gene lecA, encoding for a cytotoxic galactophilic lectin and swarming motility protein. Strain M9-54-1 also reduced brine shrimp mortality caused by Vibrio coralliilyticus VibC-Oc-193, showing potential as a biocontrol agent in aquaculture.

Synthesis and Supramolecular Functional Assemblies of Ratiometric pH Probes.

Tracking pH with spatiotemporal resolution is a critical challenge for synthetic chemistry, chemical biology and beyond. Over the last decade, different small probes and supramolecular systems have emerged for in cellulo or in vivo pH tracking. However, pH reporting still presents critical limitations, such as background reduction, improved sensor stability, cell targeting, endosomal escape, near- and far-infrared ratiometric pH tracking and adaption to new imaging techniques (i.e., super-resolution). These challenges will require the combined efforts of synthetic and supramolecular chemistry working together to develop the next generation of smart materials that will resolve current limitations. Herein, recent advances in the synthesis of small fluorescent probes, together with new supramolecular functional systems employed for pH tracking, are described with an emphasis on ratiometric probes. The combination of organic synthesis and stimuli-responsive supramolecular functional materials will be essential to solve future challenges of pH tracking, such as improved signal to noise ratio, on target activation and microenvironment reporting.

Psychrobacillus vulpis sp. nov., a new species isolated from faeces of a red fox in Spain.

A facultative anaerobic, chemoheterotrophic, endospore-forming, Gram-stain-positive rod, designated as strain Z8T, was isolated from red fox (Vulpes vulpes) faeces sampled at Tablas de Daimiel National Park, Ciudad Real, Spain. Strain Z8T grew at 0-37 °C (optimum, 28 °C), in the presence of 0-5.5 % (w/v) NaCl (2.5 %, w/v) and at pH 6-10 (pH 7). The strain was motile and positive for catalase, oxidase, H2S and siderophore production, acid and alkaline phosphatases, and N-acetylglucosamine, adipic acid and malate assimilation. It hydrolysed starch, DNA, l-tyrosine, Tween 20, Tween 80 and lecithovitellin. Phylogenetic analysis of the 16S rRNA gene sequence indicated that strain Z8T is a member of the genus Psychrobacillus, showing high sequence similarity to Psychrobacillus lasiicapitis NEAU-3TGS17T (99.2 %) and Psychrobacillus soli NHI-2TT (99.1 %), and around 98 % to other known species of the genus Psychrobacillus. Digital DNA-DNA hybridization and average nucleotide identity values were lower than 24 and 79 %, respectively, with the most related species. In silico G+C content was 35.9 mol%. The major cellular fatty acids of strain Z8T were iso-C14 : 0, iso-C15 : 0 and anteiso-C15 : 0. The novel strain contained diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol as predominant polar lipids, and the main respiratory isoprenoid quinone was MK-8. Based on the 16S rRNA phylogenetic analysis, together with MLSA (recA, rpoB and gyrB), phylogenomic, chemotaxonomic and phenotypic results, we demonstrate that strain Z8T represents a novel species of the genus Psychrobacillus, for which the name Psychrobacillus vulpis sp. nov., is proposed. The type strain is Z8T (=CECT 9721T=LMG 31001T).

Roseovarius bejariae sp. nov., a moderately halophilic bacterium isolated from a hypersaline steep-sided river bed.

An aerobic, Gram-stain-negative ovoid, designated as strain A21T, was isolated using the dilution-to-extinction method from a soil sample taken from Rambla Salada, an athalassohaline habitat located in Murcia (south-eastern Spain). Strain A21T is non-motile, has a respiratory metabolism and grows at NaCl concentrations within the range 0.5-15 % (w/v) [optimum, 5 % (w/v)], at 5-35 °C (optimum, 28 °C) and at pH 6-8 (optimum, pH 7.0). This strain is positive for catalase activity, oxidase activity and nitrate reduction. The 16S rRNA gene sequence indicates that it belongs to the genus Roseovarius in the class Alphaproteobacteria. The most closely related species are Roseovarius pacificus and Roseovarius halotolerans to which the strain A21T shows 16S rRNA gene sequence similarity values of 98.06 and 97.7 %, respectively. The average nucleotide identity in blast and digital DNA-DNA hybridization values between strain A21T and R. pacificus LMG 24575T are 76.8 and 21 %, respectively. The DNA G+C content based on the genome is 61.28 mol%. The major fatty acids (>5 % of the total fatty acids) of strain A21T are C18 : 1 ω7c/C18 : 1 ω6c and C16 : 0. The only detected isoprenoid quinone in strain A21T is ubiquinone 10 (Q-10). The polar lipid profile contains phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol and three unidentified polar lipids. Based on the phylogenetic, genotypic, phenotypic and chemotaxonomic data, the strain represents a novel species of the genus Roseovarius, for which the name Roseovarius bejariae sp. nov. is proposed. Strain A21T (=CECT 9817T=LMG 31311T) is the type strain.

Correction: Functionalized fluorescent terephthalate monomers and their attempted polyester formation.

Correction for 'Functionalized fluorescent terephthalate monomers and their attempted polyester formation' by Yvonne S. L. Choo et al., Org. Biomol. Chem., 2020, 18, 8735-8745, DOI: 10.1039/D0OB01533D.

Influence of the reducing-end anomeric configuration of the Man9 epitope on DC-SIGN recognition.

High-mannose (Man9GlcNAc2) is the main carbohydrate unit present in viral envelope glycoproteins such as gp120 of HIV and the GP1 of Ebola virus. This oligosaccharide comprises the Man9 epitope conjugated to two terminal N-acetylglucosamines by otherwise rarely-encountered ß-mannose glycosidic bond. Formation of this challenging linkage is the bottleneck of the few synthetic approaches described to prepare high mannose. Herein, we report the synthesis of the Man9 epitope with both alpha and beta configurations at the reducing end, and subsequent evaluation of the impact of this configuration on binding to natural receptor of high-mannose, DC-SIGN. Using fluorescence polarization assays, we demonstrate that both anomers bind to DC-SIGN with comparable affinity. These relevant results therefore indicate that the more synthetically-accesible Man9 alpha epitope may be deployed as ligand for DC-SIGN in both in vitro and in vivo biological assays.

Efficient Ab Initio Multiplet Calculations for Magnetic Adatoms on MgO.

Scanning probe microscopy and spectroscopy, and more recently, single-atom electron spin resonance, have allowed the direct observation of electron dynamics at the atomic limit. The interpretation of data is strongly dependent on model Hamiltonians. However, fitting effective spin Hamiltonians to experimental data lacks the ability to explore a vast number of potential systems of interest. By using plane-wave density functional theory as starting point, we build a multiplet Hamiltonian making use of maximally localized Wannier functions. The Hamiltonian contains spin-orbit and electron-electron interactions needed to obtain the relevant spin dynamics. The resulting reduced Hamiltonian is solved by exact diagonalization. We compare three prototypical cases of 3d transition metals Mn (total spin S = 5/2), Fe (S = 2), and Co (S = 3/2) on MgO with experimental data and find that our calculations can accurately predict the spin orientation and anisotropy of the magnetic adatom. Our method does not rely on experimental input and allows us to explore and predict the fundamental magnetic properties of adatoms on surfaces.

Synthesis of Highly Efficient Multivalent Disaccharide/[60]Fullerene Nanoballs for Emergent Viruses.

After the last epidemic of the Zika virus (ZIKV) in Brazil that peaked in 2016, growing evidence has been demonstrated of the link between this teratogenic flavivirus and microcephaly cases. However, no vaccine or antiviral drug has been approved yet. ZIKV and Dengue viruses (DENV) entry to the host cell takes place through several receptors, including dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), so that the blockade of this receptor through multivalent glycoconjugates supposes a promising biological target to inhibit the infection process. In order to get enhanced multivalency in biocompatible systems, tridecafullerenes appended with up to 360 1,2-mannobiosides have been synthesized using a strain-promoted cycloaddition of azides to alkynes (SPAAC) strategy. These systems have been tested against ZIKV and DENV infection, showing an outstanding activity in the picomolar range.

Glycosylated Cell-Penetrating Peptides (GCPPs).

The cell membrane regulates the exchange of molecules and information with the external environment. However, this control barrier hinders the delivery of exogenous bioactive molecules that can be applied to correct cellular malfunctions. Therefore, the traffic of macromolecules across the cell membrane represents a great challenge for the development of the next generation of therapies and diagnostic methods. Cell-penetrating peptides are short peptide sequences capable of delivering a broad range of biomacromolecules across the cellular membrane. However, penetrating peptides still suffer from limitations, mainly related to their lack of specificity and potential toxicity. Glycosylation has emerged as a potential promising strategy for the biological improvement of synthetic materials. In this work we have developed a new convergent strategy for the synthesis of penetrating peptides functionalized with glycan residues by an oxime bond connection. The uptake efficiency and intracellular distribution of these glycopeptides have been systematically characterized by means of flow cytometry and confocal microscopy and in zebrafish animal models. The incorporation of these glycan residues into the peptide structure influenced the internalization efficiency and cellular toxicity of the resulting glycopeptide hybrids in the different cell lines tested. The results reported herein highlight the potential of the glycosylation of penetrating peptides to modulate their activity.

Draft genome sequence of Lactobacillus plantarum C4 (CECT 9567), a potential probiotic strain isolated from kefir.

Lactobacillus plantarum C4 (CECT 9567) was isolated from kefir and has been extensively studied because of its probiotic properties. Here we report the genome sequence of this strain. The genome consists of 3,221,350 bp, and contains 3058 CDSs with an average G + C content of 44.5%. The genome harbors genes encoding the AraC-family transcription regulator, the penicillin-binding protein Pbp2A, and the Na+/H+ antiporter NapA3, which have important roles in the survival of lactobacilli in the gastrointestinal tract. Also, the genome encodes the catalase KatE, NADH peroxidase and glutathione peroxidase, which enable anaerobic respiration, and a nitrate reductase complex, which enable anaerobic respiration. Additionally, genes encoding plantaricins and sactipeptides, and genes involved in the use of fructooligosaccharides and in the production of butyric acid were also identified. BLASTn analysis revealed that 91.4% of CDSs in C4 genome aligned with those of the reference strain L. plantarum WCFS1, with a mean identity of 98.96%. The genome information of L. plantarum C4 provides the basis for understanding the probiotic properties of C4 and to consider its use as a potential component of functional foods.

A Quorum-Sensing Inhibitor Strain of Vibrio alginolyticus Blocks Qs-Controlled Phenotypes in Chromobacterium violaceum and Pseudomonas aeruginosa.

The cell density-dependent mechanism, quorum sensing (QS), regulates the expression of virulence factors. Its inhibition has been proposed as a promising new strategy to prevent bacterial pathogenicity. In this study, 827 strains from the microbiota of sea anemones and holothurians were screened for their ability to produce quorum-sensing inhibitor (QSI) compounds. The strain M3-10, identified as Vibrio alginolyticus by 16S rRNA gene sequencing, as well as ANIb and dDDH analyses, was selected for its high QSI activity. Bioassay-guided fractionation of the cell pellet extract from a fermentation broth of strain M3-10, followed by LC-MS and NMR analyses, revealed tyramine and N-acetyltyramine as the active compounds. The QS inhibitory activity of these molecules, which was confirmed using pure commercially available standards, was found to significantly inhibit Chromobacterium violaceum ATCC 12472 violacein production and virulence factors, such as pyoverdine production, as well as swarming and twitching motilities, produced by Pseudomonas aeruginosa PAO1. This constitutes the first study to screen QSI-producing strains in the microbiota of anemones and holothurians and provides an insight into the use of naturally produced QSI as a possible strategy to combat bacterial infections.

Maleimide and Cyclooctyne-Based Hexakis-Adducts of Fullerene: Multivalent Scaffolds for Copper-Free Click Chemistry on Fullerenes.

The synthesis of multivalent systems based on hexakis-adducts of [60]fullerene employing a biocompatible copper-free click chemistry strategy has been accomplished. A symmetric hexakis-adduct of fullerene bearing 12 maleimide units (3) is reported, and it has been employed to carry out the thiol-maleimide Michael addition. To achieve orthogonal click addition, an asymmetric derivative bearing one maleimide and 10 cyclooctynes has been synthesized. The sequential and one-pot transformations of the two clickable groups have been explored, finding the best results in the case of the one-pot experiment. This route has been used to obtain a biocompatible hexakis-adduct appended with two different biomolecules, carbohydrates, and amino acids.

Topological Defects in Hyperbranched Glycopolymers Enhance Binding to Lectins.

Central scaffold topology and carbohydrate density are important features in determining the binding mechanism and potency of synthetic multivalent of poly- versus monodisperse carbohydrate systems against a model plant toxin (Ricinus communis agglutinin (RCA120 )). Lower densities of protein receptors favour the use of heterogeneous, polydisperse glycoconjugate presentations, as determined by surface plasmon resonance and dynamic light scattering.

Glycodendrimers as Chondroitin Sulfate Mimetics: Synthesis and Binding to Growth Factor Midkine.

Chondroitin sulfate (CS) is a member of the glycosaminoglycan (GAG) family, a class of polysaccharides implicated in relevant biological functions. The structural complexity of these carbohydrates demands the development of simple glycomimetics as useful tools to study the biological processes in which GAGs are involved. In this work we described the synthesis of the disaccharide unit of the CS-E (GlcA-GalNAc(4,6-di-OSO3 )), in a multivalent presentation. Using a fluorescence polarization competition assay we have demonstrated that a hexavalent dendrimer of this disaccharide interact with midkine, in the low micromolar range. This result highlights the potency of these disaccharide-displaying multivalent systems as interesting mimetics of longer and synthetically more complex GAG oligosaccharides.