Immunoglobulin G (IgG) Fc receptors play a critical role in linking IgG antibody-mediated immune responses with cellular effector functions. A high resolution map of the binding site on human IgG1 for human Fc gamma RI, Fc gamma RIIA, Fc gamma RIIB, Fc gamma RIIIA, and FcRn receptors has been determined. A common set of IgG1 residues is involved in binding to all Fc gamma R; Fc gamma RII and Fc gamma RIII also utilize residues outside this common set. In addition to residues which, when altered, abrogated binding to one or more of the receptors, several residues were found that improved binding only to specific receptors or simultaneously improved binding to one type of receptor and reduced binding to another type. Select IgG1 variants with improved binding to Fc gamma RIIIA exhibited up to 100% enhancement in antibody-dependent cell cytotoxicity using human effector cells; these variants included changes at residues not found at the binding interface in the IgG/Fc gamma RIIIA co-crystal structure (Sondermann, P., Huber, R., Oosthuizen, V., and Jacob, U. (2000) Nature 406, 267-273). These engineered antibodies may have important implications for improving antibody therapeutic efficacy.
The Binding is a dark chocolate slice of cake with a surprising, satisfying seam of raspberry running through it. It is a rich, gothic entertainment that explores what books have trapped inside them and reminds us of the power of storytelling. Spellbinding.
Perceptual representations depend on distributed neural codes for relaying the parts and properties of objects. Some mechanism is needed to 'bind' the information relating to each object and to distinguish it from others. Possible candidates include cells tuned to conjunctions of features, spatial attention, and synchronized firing across separate but interconnected areas of the brain. Deficits in neurological patients suggest a role for the parietal cortex in the binding process. Several current models combine these ideas.
The Binding Site is a global specialist protein diagnostics company engaged in the research, development, manufacture and distribution of innovative tests used for the detection of cancers and immune disorders. It is a business centered on the idea of working in collaboration with its partners and customers to lead the way in specialised medical diagnostics. The Company is headquartered in Birmingham, UK and has a direct presence in over 23 countries, employing over 1,100 people worldwide. Read more on www.bindingsite.com
Binding corporate rules (BCR) are data protection policies adhered to by companies established in the EU for transfers of personal data outside the EU within a group of undertakings or enterprises. Such rules must include all general data protection principles and enforceable rights to ensure appropriate safeguards for data transfers. They must be legally binding and enforced by every member concerned of the group.
Companies must submit binding corporate rules for approval to the competent data protection authority in the EU. The authority will approve the BCRs in accordance with the consistency mechanism set out in Article 63 of the GDPR. This procedure may involve several supervisory authorities since the group applying for approval of its BCRs may have entities in more than one Member State. The competent authority communicates its draft decision to the European Data Protection Board, which will issue its opinion on the binding corporate rules. When the BCRs have been finalised in accordance with the EDPB opinion, the competent authority will approve the BCRs.
The Article 29 Working Party adopted the following documents, which have been endorsed by the EDPB. These documents describe the procedure of approval and provide guidance on the structure and requirements of binding corporate rules.
In THE BINDING, happy couple Emma (Mia Maestro) and Francesco (Ricardo Samarico) travel with her daughter Sofia (Giulia Patrignani) to surprise his mother, Teresa (Mariella Lo Sardo) at the rural southern Italian mansion where he grew up. Inside these dark rooms, strange prayers are whispered. Teresa and her friend Sabrina seem grim and worried. When a tarantula bites Sofia, evil spirits are unleashed, and so is the backstory. Long ago, young Francesco fell for a local girl named Ada. He got her pregnant, but he wasn't "ready" to be a father and wanted her to abort the pregnancy. When Ada said no, Francesco turned to ancestral black magic to end the pregnancy, but bungled it. He must have read the instructions wrong, because although Ada lost the baby, she turned into someone badly in need of an exorcist. The lovely girl cracked mirrors with her gaze, growled like Darth Vader, and disappeared into the surrounding forest for many years. When happy Francesco shows up with fiancée Emma and Sofia, Ada comes out of the woodwork and "binds" Sofia to her evil self, with the goal of also binding Francesco so they can live an undead life in a nuclear family, happily ever after.
This calculator calculates the amount of fabric required to bind your quilt giventhe quilt's dimensions (width and length) and the binding strip width.The calculator provides 2 calculations:"Regular" binding - this is where the binding strips are cut parallel to the width of fabric on a bolt of fabric.Bias binding - this is where the binding strips are cut on the bias.To use the calculator,specify the width of the fabric(the calculator defaults to a value of 43 inches)along with the width and length of the quilt,and the desired binding strip width.The calculator provides:The total length of the binding (the perimeter of the quilt).The amount of fabric needed to cut the binding strips.The number of strips you must cut from the fabric ("regular" binding only).Note on Flange Binding:a flange binding consists of 2 fabric strips sewn together along the long edge;the two strips may be of different fabrics.One strip is 1/4" wider than the other to account for the seam allowance when sewn together.If you are making a flange binding and need to calculate the yardage required,simply run the binding calculator twice, once for each striptaking care to specify the correct binding strip width for each strip.Choose a calculatorBacking and BattingBindingBorderDie Cut LetterFabric Measurement ConversionPiece CountPieces to Yardage AreaProject CostSashingSet in and Corner TriangleShapeSlit N Sew Fabric CalculatorSquare in a SquareStripWidth of Fabric Yardage ConversionSlit 'N Sew Double Wedding Ring Template
Functions for RNA-binding proteins in orchestrating plant development and environmental responses are well established. However, the lack of a genome-wide view of their in vivo binding targets and binding landscapes represents a gap in understanding the mode of action of plant RNA-binding proteins. Here, we adapt individual nucleotide resolution crosslinking and immunoprecipitation (iCLIP) genome-wide to determine the binding repertoire of the circadian clock-regulated Arabidopsis thaliana glycine-rich RNA-binding protein AtGRP7.
We have established iCLIP for plants to identify target transcripts of the RNA-binding protein AtGRP7. This paves the way to investigate the dynamics of posttranscriptional networks in response to exogenous and endogenous cues.
We chose to establish iCLIP for Arabidopsis, using Arabidopsis thaliana glycine-rich RNA-binding protein 7 (AtGRP7) as a paradigm. AtGRP7 is controlled by the circadian clock, an endogenous timekeeper that prepares organisms for the periodic changes of day and night . AtGRP7 consists of a single RRM and a namesake glycine-rich stretch. The AtGRP7 transcript oscillates with a peak in the evening, and the oscillations persist in continuous light [12, 13]. Ectopic over-expression of AtGRP7 (AtGRP7-ox) leads to damping of the endogenous AtGRP7 transcript oscillations: Binding of AtGRP7 to its own pre-mRNA causes a shift to an alternative splice form retaining part of the intron with a premature termination codon (PTC) that is degraded via nonsense-mediated decay (NMD) [14, 15]. Elevated levels of AtGRP7 also negatively regulate the paralog AtGRP8 through alternative splicing and NMD. Furthermore, AtGRP7 regulates alternative splicing of a suite of downstream targets . Additionally, AtGRP7 functions as an RNA chaperone . Mutation of the conserved Arg49 in the RNA-binding domain (R49Q) abolishes in vivo RNA binding and function [18, 19]. AtGRP7 is involved in a suite of physiological processes, including circadian timekeeping, cold responses, phytohormone responses, and flowering time control [20,21,22]. To comprehensively understand how AtGRP7 exerts its diverse functions, determination of its target transcripts and binding landscape at a genome-wide scale is of central importance.
Here, we determined AtGRP7 targets by iCLIP and a parallel RIP-seq analysis for independent validation. In plants expressing an AtGRP7-GREEN FLUORESCENT PROTEIN (GFP) fusion we identified significant crosslink sites in 858 target transcripts that were not detected in plants expressing the RNA-binding dead variant AtGRP7 R49Q-GFP, or GFP alone. Of these targets, 452 were also identified by RIP-seq following formaldehyde crosslinking, defining a set of high-confidence binders. In the vicinity of the crosslink sites, UC rich motifs were enriched. To investigate whether the identified in vivo targets are regulated by AtGRP7 at the mRNA level, we performed total RNA-seq of AtGRP7 loss-of-function and overexpressing plants. Direct binding targets appear to be predominantly negatively regulated by AtGRP7. In particular, circadian transcript oscillations are damped in AtGRP7-overexpressing plants.
This confirmation of targets suggests that the overlap between iCLIP and RIP-seq represents high-confidence in vivo targets of AtGRP7. Moreover, binding of transcripts encoding the transcription factors ETHYLENE RESPONSE FACTOR 4 (ERF4; At3g15210), WRKY33 (At2g38470), and SALT TOLERANCE ZINC FINGER (STZ; At1g27730), which were identified by RIP-seq only, was validated in independent biological replicates by RIP-qPCR. Their absence from the iCLIP targets could be due to the reduced crosslinking efficiency of UV light or because they represent indirect targets. 041b061a72