Conformational Flexibility of A Highly Conserved Helix Controls Cryptic Pocket Formation in FtsZ

Mycobacterium tuberculosis is responsible for more than 1.6 million deaths each year. One potential antibacterial target in M. tuberculosis is filamentous temperature sensitive protein Z (FtsZ), which is the bacterial homologue of mammalian tubulin, a validated cancer target. M. tuberculosis FtsZ function is essential, with its inhibition leading to arrest of cell division, elongation of the bacterial cell and eventual cell death. However, the development of potent inhibitors against FtsZ has been a challenge owing to the lack of structural information. Here we report multiple crystal structures of M. tuberculosis FtsZ in complex with a coumarin analogue. The 4-hydroxycoumarin binds exclusively to two novel cryptic pockets in nucleotide-free FtsZ, but not to the binary FtsZ-GTP or GDP complexes. Our findings provide a detailed understanding of the molecular basis for cryptic pocket formation, controlled by the conformational flexibility of the H7 helix, and thus reveal an important structural and mechanistic rationale for coumarin antibacterial activity

Autohydrolysis followed by ionic liquid treatment for Eucalyptus globulus wood fractionation

The 2030 Agenda for Sustainable Development recognises the need for a green and sustainable chemistry and engineering [1]. In this context, cleaner processes require the substitution of organic solvents by less harmful solvents. In addition, the solvent selection for a biomass processing is crucial for the environmental sustainability and feasibility of a biorefinery [2]. In this work, water and the ionic liquid 1-ethyl-3-methylimidazolium acetate ([C2mim][OAc]) were chosen as green solvents for a selective fractionation of Eucalyptus globulus wood in order to valorise their main fractions (hemicellulose, cellulose and lignin). Two sequential stages were proposed for the biomass processing. First, an autohydrolysis step allowed the hemicellulose solubilisation and its recovery as oligosaccharides in the aqueous liquid phase, yielding a solid phase composed by 60 % glucan and 34 % lignin. Second, a treatment with [C2mim][OAc] was evaluated for the delignification of the autohydrolysed biomass. Optimisation of operational conditions (temperature and time) of the ionic liquid treatment was performed to improve the enzymatic saccharification of cellulose remaining in the solid phase and to solubilise lignin. The proposed process configuration is expected to contribute towards the development of integrated biorefineries based on hardwood biomass.This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2019 unit, BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional doNorte, the EcoTech project (POCI01-0145-FEDER-032206). Aloia Romaní thanks the Iacobus Program (European Territorial Cooperation Partnership Galicia – Norte de Portugal) for a mobility fellowship.info:eu-repo/semantics/publishedVersio

Characterization of a putative grapevine Zn transporter, VvZIP3, suggests its involvement in early reproductive development in Vitis vinifera L

Gonzalez, E (reprint author), Univ Talca, Inst Biol Vegetal & Biotecnol, Talca, Chile.Background: Zinc (Zn) deficiency is one of the most widespread mineral nutritional problems that affect normal development in plants. Because Zn cannot passively diffuse across cell membranes, it must be transported into intracellular compartments for all biological processes where Zn is required. Several members of the Zinc-regulated transporters, Iron-regulated transporter-like Protein (ZIP) gene family have been characterized in plants, and have shown to be involved in metal uptake and transport. This study describes the first putative Zn transporter in grapevine. Unravelling its function may explain an important symptom of Zn deficiency in grapevines, which is the production of clusters with fewer and usually smaller berries than normal. Results: We identified and characterized a putative Zn transporter from berries of Vitis vinifera L., named VvZIP3. Compared to other members of the ZIP family identified in the Vitis vinifera L. genome, VvZIP3 is mainly expressed in reproductive tissue - specifically in developing flowers - which correlates with the high Zn accumulation in these organs. Contrary to this, the low expression of VvZIP3 in parthenocarpic berries shows a relationship with the lower Zn accumulation in this tissue than in normal seeded berries where its expression is induced by Zn. The predicted protein sequence indicates strong similarity with several members of the ZIP family from Arabidopsis thaliana and other species. Moreover, VvZIP3 complemented the growth defect of a yeast Zn-uptake mutant, ZHY3, and is localized in the plasma membrane of plant cells, suggesting that VvZIP3 has the function of a Zn uptake transporter. Conclusions: Our results suggest that VvZIP3 encodes a putative plasma membrane Zn transporter protein member of the ZIP gene family that might play a role in Zn uptake and distribution during the early reproductive development in Vitis vinifera L., indicating that the availability of this micronutrient may be relevant for reproductive development

New multisite observations of Delta Scuti stars V624 Tauri and HD 23194

The preliminary results of STEPHI 2006 campaign are reported.Comment: To be published in Communications in Asteroseismolgy: Special Issu

Powerful Radio Sources in the Southern Sky. II. A SWIFT X-Ray Perspective

We recently constructed the G4Jy-3CRE, a catalog of extragalactic radio sources based on the GLEAM 4-Jy (G4Jy) sample, with the aim of increasing the number of powerful radio galaxies and quasars with similar selection criteria to those of the revised release of the Third Cambridge catalog (3CR). The G4Jy-3CRE consists of a total of 264 radio sources mainly visible from the Southern Hemisphere. Here, we present an initial X-ray analysis of 89 G4Jy-3CRE radio sources with archival X- ray observations from the Neil Gehrels Swift Observatory. We reduced a total of 615 Swift observations, for about 0.89 Msec of integrated exposure time, we found X-ray counterparts for 61 radio sources belonging to the G4Jy-3CRE, 11 of them showing extended X-ray emission. The remaining 28 sources do not show any X-ray emission associated with their radio cores. Our analysis demonstrates that X-ray snapshot observations, even if lacking uniform exposure times, as those carried out with Swift, allow us to (i) verify and/or re ne the host galaxy identi cation; (ii) discover the extended X-ray emission around radio galaxies of the intracluster medium when harbored in galaxy clusters, as the case of G4Jy 1518 and G4Jy 1664, and (iii) detect X-ray radiation arising from their radio lobes, as for G4Jy 1863.Comment: 35 pages, 17 figures, 2 tables; second paper of a series, pre-proof versio

Powerful Radio Sources in the Southern Sky. I. Optical Identifications

Since the early sixties, our view of radio galaxies and quasars has been drastically shaped by discoveries made thanks to observations of radio sources listed in the Third Cambridge catalog and its revised version (3CR). However, the largest fraction of data collected to date on 3CR sources was performed with relatively old instruments, rarely repeated and/or updated. Importantly, the 3CR contains only objects located in the Northern Hemisphere thus having limited access to new and innovative astronomical facilities. To mitigate these limitations we present a new catalog of powerful radio sources visible from the Southern Hemisphere, extracted from the GLEAM 4-Jy (G4Jy) catalog and based on equivalent selection criteria as the 3CR. This new catalog, named G4Jy- 3CRE, where the E stands for "equivalent", lists a total of 264 sources at declination below -5 degrees and with 9 Jy limiting sensitivity at ~178 MHz. We explored archival radio maps obtained with different surveys and compared then with optical images available in the Pan-STARRS, DES and DSS databases to search for optical counterparts of their radio cores. We compared mid-infrared counterparts, originally associated in the G4Jy, with the optical ones identified here and we present results of a vast literature search carried out to collect redshift estimates for all G4Jy-3CRE sources resulting in a total of 145 reliable z measurements.Comment: 72 pages, 35 figures, 5 Table

Considerations in Building and Fielding MPDV

Author Institution: National Security Technologies, LLCSlides presented at the 6th Annual Photonic Doppler Velocimetry (PDV) Workshop held at Lawrence Livermore National Laboratory, Livermore, California, November 3-4, 2011

First-in-class humanized FSH blocking antibody targets bone and fat

Blocking the action of FSH genetically or pharmacologically in mice reduces body fat, lowers serum cholesterol, and increases bone mass, making an anti-FSH agent a potential therapeutic for three global epidemics: obesity, osteoporosis, and hypercholesterolemia. Here, we report the generation, structure, and function of a first-in-class, fully humanized, epitope-specific FSH blocking antibody with a KD of 7 nM. Protein thermal shift, molecular dynamics, and fine mapping of the FSH-FSH receptor interface confirm stable binding of the Fab domain to two of five receptor-interacting residues of the FSHβ subunit, which is sufficient to block its interaction with the FSH receptor. In doing so, the humanized antibody profoundly inhibited FSH action in cell-based assays, a prelude to further preclinical and clinical testing

Models of Neutrino Masses and Mixings

We review theoretical ideas, problems and implications of neutrino masses and mixing angles. We give a general discussion of schemes with three light neutrinos. Several specific examples are analyzed in some detail, particularly those that can be embedded into grand unified theories.Comment: 44 pages, 2 figures, version accepted for publication on the Focus Issue on 'Neutrino Physics' edited by F.Halzen, M.Lindner and A. Suzuki, to be published in New Journal of Physics

Differential Phosphorylation of Ribosomal Proteins in Arabidopsis thaliana Plants during Day and Night

Protein synthesis in plants is characterized by increase in the translation rates for numerous proteins and central metabolic enzymes during the day phase of the photoperiod. The detailed molecular mechanisms of this diurnal regulation are unknown, while eukaryotic protein translation is mainly controlled at the level of ribosomal initiation complexes, which also involves multiple events of protein phosphorylation. We characterized the extent of protein phosphorylation in cytosolic ribosomes isolated from leaves of the model plant Arabidopsis thaliana harvested during day or night. Proteomic analyses of preparations corresponding to both phases of the photoperiod detected phosphorylation at eight serine residues in the C-termini of six ribosomal proteins: S2-3, S6-1, S6-2, P0-2, P1 and L29-1. This included previously unknown phosphorylation of the 40S ribosomal protein S6 at Ser-231. Relative quantification of the phosphorylated peptides using stable isotope labeling and mass spectrometry revealed a 2.2 times increase in the day/night phosphorylation ratio at this site. Phosphorylation of the S6-1 and S6-2 variants of the same protein at Ser-240 increased by the factors of 4.2 and 1.8, respectively. The 1.6 increase in phosphorylation during the day was also found at Ser-58 of the 60S ribosomal protein L29-1. It is suggested that differential phosphorylation of the ribosomal proteins S6-1, S6-2 and L29-1 may contribute to modulation of the diurnal protein synthesis in plants