247 research outputs found

    Three New Coordination Compounds with Push-Pull Ligand p

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    International audienceFrom ethanolic solutions containing p-aminobenzonitrile (4ABN) and the respective metal salt three new coordination compounds were obtained and their crystal structures solved and refined from X-ray single-crystal diffraction data: [Ag(4ABN)4/2]BF4 (P 21/n, Z = 4) (1), [Cu(4ABN)4/2(H2O)2](NO3)2 x 2 H2O (P -1, Z = 2) (2) and [Co(4ABN)2(H2O)2Cl2] (P 21/n, Z = 2) (3). 1 is a coordination polymer with a distorted tetrahedral AgN4 coordination and layered polymeric [Ag(4ABN)4] cations, which are held together by van der Waals interactions. It represents the first homoleptic complex of 4ABN. In 2 Jahn-Teller distorted CuN4O2 octahedra are connected to polymeric chain-like [Cu(4ABN)4/2(H2O)2] cations, which are interconnected by hydrogen bonds including further water molecules and NO3- anions. 3 is a complex with an octahedral CoCl2N2O2 coordination. In the solid state structure, they are held together by N-H...Cl hydrogen bonds

    The C-Terminal Domain of the MutL Homolog from Neisseria gonorrhoeae Forms an Inverted Homodimer

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    The mismatch repair (MMR) pathway serves to maintain the integrity of the genome by removing mispaired bases from the newly synthesized strand. In E. coli, MutS, MutL and MutH coordinate to discriminate the daughter strand through a mechanism involving lack of methylation on the new strand. This facilitates the creation of a nick by MutH in the daughter strand to initiate mismatch repair. Many bacteria and eukaryotes, including humans, do not possess a homolog of MutH. Although the exact strategy for strand discrimination in these organisms is yet to be ascertained, the required nicking endonuclease activity is resident in the C-terminal domain of MutL. This activity is dependent on the integrity of a conserved metal binding motif. Unlike their eukaryotic counterparts, MutL in bacteria like Neisseria exist in the form of a homodimer. Even though this homodimer would possess two active sites, it still acts a nicking endonuclease. Here, we present the crystal structure of the C-terminal domain (CTD) of the MutL homolog of Neisseria gonorrhoeae (NgoL) determined to a resolution of 2.4 Å. The structure shows that the metal binding motif exists in a helical configuration and that four of the six conserved motifs in the MutL family, including the metal binding site, localize together to form a composite active site. NgoL-CTD exists in the form of an elongated inverted homodimer stabilized by a hydrophobic interface rich in leucines. The inverted arrangement places the two composite active sites in each subunit on opposite lateral sides of the homodimer. Such an arrangement raises the possibility that one of the active sites is occluded due to interaction of NgoL with other protein factors involved in MMR. The presentation of only one active site to substrate DNA will ensure that nicking of only one strand occurs to prevent inadvertent and deleterious double stranded cleavage

    Genetic and antigenic variation of the bovine tick-borne pathogen Theileria parva in the Great Lakes region of Central Africa

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    BACKGROUND : Theileria parva causes East Coast fever (ECF), one of the most economically important tick-borne diseases of cattle in sub-Saharan Africa. A live immunisation approach using the infection and treatment method (ITM) provides a strong long-term strain-restricted immunity. However, it typically induces a tick-transmissible carrier state in cattle and may lead to spread of antigenically distinct parasites. Thus, understanding the genetic composition of T. parva is needed prior to the use of the ITM vaccine in new areas. This study examined the sequence diversity and the evolutionary and biogeographical dynamics of T. parva within the African Great Lakes region to better understand the epidemiology of ECF and to assure vaccine safety. Genetic analyses were performed using sequences of two antigencoding genes, Tp1 and Tp2, generated among 119 T. parva samples collected from cattle in four agro-ecological zones of DRC and Burundi. RESULTS : The results provided evidence of nucleotide and amino acid polymorphisms in both antigens, resulting in 11 and 10 distinct nucleotide alleles, that predicted 6 and 9 protein variants in Tp1 and Tp2, respectively. Theileria parva samples showed high variation within populations and a moderate biogeographical sub-structuring due to the widespread major genotypes. The diversity was greater in samples from lowlands and midlands areas compared to those from highlands and other African countries. The evolutionary dynamics modelling revealed a signal of selective evolution which was not preferentially detected within the epitope-coding regions, suggesting that the observed polymorphism could be more related to gene flow rather than recent host immune-based selection. Most alleles isolated in the Great Lakes region were closely related to the components of the trivalent Muguga vaccine. CONCLUSIONS : Our findings suggest that the extensive sequence diversity of T. parva and its biogeographical distribution mainly depend on host migration and agro-ecological conditions driving tick population dynamics. Such patterns are likely to contribute to the epidemic and unstable endemic situations of ECF in the region. However, the fact that ubiquitous alleles are genetically similar to the components of the Muguga vaccine together with the limited geographical clustering may justify testing the existing trivalent vaccine for cross-immunity in the region.Additional file 1: Table S1. Cattle blood sample distribution across agroecological zones.Additional file 2: Table S2. Nucleotide and amino acid sequences of Tp1 and Tp2 antigen epitopes from T. parva Muguga reference sequence.Additional file 3: Table S3. Characteristics of 119 T. parva samples obtained from cattle in different agro-ecological zones (AEZs) of The Democratic Republic of Congo and Burundi.Additional file 4: Figure S1. Multiple sequence alignment of the 11 Tp1 gene alleles obtained in this study.Additional file 5: Table S4. Estimates of evolutionary divergence between gene alleles for Tp1 and Tp2, using proportion nucleotide distance.Additional file 6: Table S5. Tp1 and Tp2 genes alleles with their corresponding antigen variants.Additional file 7: Table S6. Amino acid variants of Tp1 and Tp2 CD8+ T cell target epitopes of T. parva from DRC and Burundi.Additional file 8: Figure S2. Multiple sequence alignment of the 10 Tp2 gene alleles obtained in this study.Additional file 9: Table S7. Distribution of Tp1 gene alleles of T. parva from cattle and buffalo in the sub-Saharan region of Africa.Additional file 10: Table S8. Distribution of Tp2 gene alleles of T. parva from cattle and buffalo in the sub-Saharan region of Africa.Additional file 11: Figure S3. Neighbor-joining tree showing phylogenetic relationships among 48 Tp1 gene alleles described in Africa.Additional file 12: Figure S4. Phylogenetic tree showing the relationships among concatenated Tp1 and Tp2 nucleotide sequences of 93 T. parva samples from cattle in DRC and Burundi.This study is part of the PhD work supported by the University of Namur (UNamur, Belgium) through the UNamur-CERUNA institutional PhD grant awarded to GSA for bioinformatic analyses, interpretation of data and manuscript write up in Belgium. The laboratory aspects (molecular biology analysis) of the project were supported by the BecA-ILRI Hub through the Africa Biosciences Challenge Fund (ABCF) programme. The ABCF Programme is funded by the Australian Department for Foreign Affairs and Trade (DFAT) through the BecA-CSIRO partnership; the Syngenta Foundation for Sustainable Agriculture (SFSA); the Bill & Melinda Gates Foundation (BMGF); the UK Department for International Development (DFID); and the Swedish International Development Cooperation Agency (Sida). The ABCF Fellowship awarded to GAS was funded by BMGF grant (OPP1075938). Sample collection, field equipment and preliminary sample processing were supported through the “Theileria” project co-funded to the Université Evangélique en Afrique (UEA) by the Agence Universitaire de la Francophonie (AUF) and the Communauté Economique des Pays des Grands Lacs (CEPGL). The International Foundation for Science (IFS, Stockholm, Sweden) supported the individual scholarship awarded to GSA (grant no. IFS-92890CA3) for field work and part of field equipment to the “Theileria” project.http://www.parasitesandvectors.comam2020Veterinary Tropical Disease

    The STRong lensing Insights into the Dark Energy Survey (STRIDES) 2016 follow-up campaign - I. Overview and classification of candidates selected by two techniques

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    The primary goals of the STRong lensing Insights into the Dark Energy Survey (STRIDES) collaboration are to measure the dark energy equation of state parameter and the free streaming length of dark matter. To this aim, STRIDES is discovering strongly lensed quasars in the imaging data of the Dark Energy Survey and following them up to measure time delays, high resolution imaging, and spectroscopy sufficient to construct accurate lens models. In this paper, we first present forecasts for STRIDES. Then, we describe the STRIDES classification scheme, and give an overview of the Fall 2016 follow-up campaign. We continue by detailing the results of two selection methods, the Outlier Selection Technique and a morphological algorithm, and presenting lens models of a system, which could possibly be a lensed quasar in an unusual configuration. We conclude with the summary statistics of the Fall 2016 campaign. Including searches presented in companion papers (Anguita et al.; Ostrovski et al.), STRIDES followed up 117 targets identifying 7 new strongly lensed systems, and 7 nearly identical quasars (NIQs), which could be confirmed as lenses by the detection of the lens galaxy. 76 candidates were rejected and 27 remain otherwise inconclusive, for a success rate in the range 6-35\%. This rate is comparable to that of previous searches like SQLS even though the parent dataset of STRIDES is purely photometric and our selection of candidates cannot rely on spectroscopic information

    Coupling changes in cell shape to chromosome segregation

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    Animal cells undergo dramatic changes in shape, mechanics and polarity as they progress through the different stages of cell division. These changes begin at mitotic entry, with cell–substrate adhesion remodelling, assembly of a cortical actomyosin network and osmotic swelling, which together enable cells to adopt a near spherical form even when growing in a crowded tissue environment. These shape changes, which probably aid spindle assembly and positioning, are then reversed at mitotic exit to restore the interphase cell morphology. Here, we discuss the dynamics, regulation and function of these processes, and how cell shape changes and sister chromatid segregation are coupled to ensure that the daughter cells generated through division receive their fair inheritance

    Conserved genes and pathways in primary human fibroblast strains undergoing replicative and radiation induced senescence

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    Additional file 3: Figure S3. Regulation of genes of Arrhythmogenic right ventricular cardiomyopathy pathway during senescence induction in HFF strains Genes of the “Arrhythmogenic right ventricular cardiomyopathy” pathway which are significantly up- (green) and down- (red) regulated (log2 fold change >1) during irradiation induced senescence (120 h after 20 Gy irradiation) in HFF strains. Orange color signifies genes which are commonly up-regulated during both, irradiation induced and replicative senescence

    Plasma and cellular fibronectin: distinct and independent functions during tissue repair

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    Fibronectin (FN) is a ubiquitous extracellular matrix (ECM) glycoprotein that plays vital roles during tissue repair. The plasma form of FN circulates in the blood, and upon tissue injury, is incorporated into fibrin clots to exert effects on platelet function and to mediate hemostasis. Cellular FN is then synthesized and assembled by cells as they migrate into the clot to reconstitute damaged tissue. The assembly of FN into a complex three-dimensional matrix during physiological repair plays a key role not only as a structural scaffold, but also as a regulator of cell function during this stage of tissue repair. FN fibrillogenesis is a complex, stepwise process that is strictly regulated by a multitude of factors. During fibrosis, there is excessive deposition of ECM, of which FN is one of the major components. Aberrant FN-matrix assembly is a major contributing factor to the switch from normal tissue repair to misregulated fibrosis. Understanding the mechanisms involved in FN assembly and how these interplay with cellular, fibrotic and immune responses may reveal targets for the future development of therapies to regulate aberrant tissue-repair processes

    Ockham’s razor for the MET-driven invasive growth linking idiopathic pulmonary fibrosis and cancer

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