1,720,982 research outputs found
Glycomimetic ligands acting as selective antagonists of L-SIGN
Full text linkDC-SIGN and L-SIGN – also referred to as Dendritic Cell-Specific Intracellular Adhesion molecules (ICAM)-3 Grabbing Non-integrin (CD209) and Liver/Lymphnode-Specific ICAM-3 Grabbing Non-integrin (CD209L), respectively – are two C-type lectin receptors (CLRs), sharing 77% of their amino acidic sequences.1 They are able to bind to glycan motifs directly expressed at the surface of different pathogens thanks to a Ca2+ ion in the binding site – the so-called Carbohydrate Receptor Domain (CRD) – suddenly inducing the activation of the initial stages of adaptive immune response.
Nevertheless, several deadly viruses – such as HIV, Ebola, hepatitis C viruses, Dengue and West Nile virus – have developed strategies to subvert the function of CLRs to escape antiviral immunity and promote infection.2 Beyond the cited microorganisms, DC-SIGN and L-SIGN have been recently found to be entry co-factors for SARS-CoV-2, promoting trans-infection of ACE2-expressing cells.3,4
Interestingly, while fundamental studies have been performed in last years to design and characterize molecules acting as inhibitors of DC-SIGN-mediated infections, the first set of mannose-based ligands for L-SIGN was reported by our group only in 2022.5 According to this paper, the tested glycomimetics could inhibit the interaction of both lectins with the SARS-CoV-2 spike glycoprotein in a Surface Plasmon Resonance (SPR) assay and are more potent than mannose by up to 36-fold (DC-SIGN) and 10-fold (L-SIGN).
In this context, we present a new set of mannose-based glycomimetics which could selectively inhibit L-SIGN against DC-SIGN. All the molecules are based on a mono-mannose scaffold, modified at position 2 with a triazole moiety
Water relations, growth, and leaf gas exchange as affected by water stress in Jatropha curcas
No full textHere we examined the response mechanisms and the strategies adopted to cope with drought stress in Jatropha curcas L. Response mechanisms to water stress were explored in three different accessions (from Brazil, Tanzania and Suriname) of J. curcas in terms of water and osmotic relations, gas exchange, PSII photochemistry, and growth performances. Plants were exposed to 18 days of water stress (irrigation was kept at 20% of water holding capacity) followed by 13 days of relief from stress. J. curcas withstands drought stress with a drought-avoidance mechanism through a water saving strategy. These responses include selective abscission of leaves, and marked decreases in net photosynthetic rates and water use efficiency. This allows plants to maintain an " above-lethal" water potential during stress, and to recover net assimilation rate promptly when water availability to the roots is resumed. The Suriname accession displayed greater reductions in net photosynthesis, maximal efficiency of PSII photochemistry (Fv/Fm), total leaf area and plant dry weight, as compared with both Tanzania and, particularly, the Brazil accession, during drought stress. Impairment of PSII photochemistry was also observed in the Suriname accession at the end of the relief period. Water-stressed J. curcas, irrespective of seed source, was capable to recover net photosynthesis to the level of the well watered counterparts by the end of the relief period. Our data allow to conclude that J. curcas may survive to drought spells of moderate intensities but, at the same time pose serious concerns for its profitable cultivation in arid/semi-arid regions worldwide
Man-based glycomimetics inhibit DC/L-SIGN interaction with SARS-CoV-2 spike protein
No full textDC-SIGN and its homologue L-SIGN are two tetrameric transmembrane C-type lectins that share 77% of their amino-acidic sequence. Despite their high similarity, some important differences are present: DC-SIGN is expressed by immature dendritic cells located on dermal and mucosal tissues and can recognize both mannosylated and fucosylated structures; while L-SIGN expression is limited to specific tissues (e.g. lungs, liver and lymph-nodes) and preferentially binds mannose-containing carbohydrates.
They are well known receptor for glycosylated pathogens (e.g. HIV-1, Ebola, Dengue) and were recently identified as entry co-factors for SARS-CoV-2. Since L-SIGN is co-expressed with ACE2 on respiratory tract cells, the need for potent and selective antagonist is real and urgent.
Over the past decades, several efforts have been made for the development of DC-SIGN ligands as inhibitors of DC-SIGN mediated infections; however, no ligands have been reported so far to bind to L-SIGN.
Here, we present the first set of mannose-based glycomimetic ligands which bind to L-SIGN in an SPR inhibition experiment showing that they inhibit binding of both DC-SIGN and L-SIGN to immobilized SARS-CoV-2 spike protein.
All the ligands examined present a mannose residue modified at position 2 with a triazole moiety, both as a part of a pseudo-dimannoside or as a monosaccharide.
The design, synthesis and activity evaluation of the ligands will be discussed
C2-Triazole-modified mannose-based L-SIGN antagonists
No full textL-SIGN - Liver/lymph node-specific ICAM-3-grabbing integrin – is a tetrameric transmembrane C-type lectin, which shares 77% amino acid sequence with DC-SIGN and displays similar activity for highly mannosylated oligosaccharides. It is expressed in human lungs in type II alveolar cells and in endothelial cells and has recently been characterized as an entry co-factor for SARS-CoV-2.
Over the past decades, important efforts have been made for the development of DC-SIGN ligands as inhibitors of DC-SIGN mediated infections; however, no ligands have been reported so far to bind to L-SIGN.
Here, we present the first set of mannose-based glycomimetic ligands which bind to L-SIGN in an SPR inhibition experiment showing that they inhibit binding of both DC-SIGN and L-SIGN to immobilized SARS-CoV-2 spike protein.
All the ligands examined present a mannose residue modified at position 2 with a triazole moiety, both as a part of a pseudo-dimannoside or as a monosaccharide. The design, synthesis and activity evaluation of the ligands will be discussed
Mannose-based glycomimetics acting as selective ligands for L-SIGN
Full text linkDC-SIGN and L-SIGN – also referred to as Dendritic Cell-Specific Intracellular Adhesion molecules (ICAM)-3 Grabbing Non-integrin (CD209) and Liver/Lymphnode-Specific ICAM-3 Grabbing Non-integrin (CD209L), respectively – are two C-type lectin receptors (CLRs), sharing 77% of their amino acidic sequences.1 They are able to bind to glycan motifs directly expressed at the surface of different pathogens thanks to a Ca2+ ion in the binding site – the so-called Carbohydrate Receptor Domain (CRD) – suddenly inducing the activation of the initial stages of adaptive immune response.
Nevertheless, several deadly viruses – such as HIV, Ebola, hepatitis C viruses, Dengue and West Nile virus – have developed strategies to subvert the function of CLRs to escape antiviral immunity and promote infection.2 Beyond the cited microorganisms, DC-SIGN and L-SIGN have been recently found to be entry co-factors for SARS-CoV-2, promoting trans-infection of ACE2-expressing cells.3
Interestingly, while fundamental studies have been performed in last years to design and characterize molecules acting as inhibitors of DC-SIGN-mediated infections, the first set of mannose-based ligands for L-SIGN was reported by our group only in 2022.4 According to this paper, the tested glycomimetics could inhibit the interaction of both lectins with the SARS-CoV-2 spike glycoprotein in a Surface Plasmon Resonance (SPR) assay and are more potent than mannose by up to 36-fold (DC-SIGN) and 10-fold (L-SIGN).
In this context, we present a new set of mannose-based glycomimetics which could selectively inhibit L-SIGN against DC-SIGN. All the molecules are based on a mono-mannose scaffold, modified at position 2 with a triazole moiety
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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