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The significance of the Drosophila transmembrane protein-tyrosine phosphatase leukocyte common antigen-related (DLAR) in motor axon guidance was studied. Segmental nerve b motor axons in DLAR-deficient embryos, bypassed their muscle destinations. Findings indicated that DLAR regulates the capability of certain motor axons to find their way along certain choice points in the developing Drosophila nervous system.

Background: ALX148, a novel CD47 blocking agent, is in clinical development for the treatment of advanced solid tumors and lymphoma. Because CD47 is highly expressed on red blood cells (RBCs), its therapeutic blockade can potentially interfere with pretransfusion compatibility testing. This study describes the interference of ALX148 in pretransfusion compatibility testing and evaluates the methods used for mitigating such interference. Study Design and Methods: Routine serologic tests were performed on six samples from four patients treated with ALX148. Antibody screening tests were performed on ALX148‐spiked plasma, and RBC testing including antigen typing was performed on ALX148‐coated RBCs. Soluble CD47 or high‐affinity signal regulatory protein α (SIRPα) monomers were used to remove the false‐positive reactivity of ALX148‐spiked plasma with or without anti‐E. Results: ALX148 caused false‐positive reactivity in antibody screening using indirect antiglobulin testing (IAT) and two‐stage papain testing. However, false‐positive reactivity was not observed at the immediate spin (IS), room temperature (RT), and 37°C phases. Direct antiglobulin testing, autologous controls, and eluates showed positive results. ALX148 did not affect blood group antigen typing performed at the IS or RT phases. The use of 50‐ to 100‐fold molar excess of soluble CD47 or 300‐fold molar excess of high‐affinity SIRPα monomers removed false‐positive reactivity in IAT without affecting anti‐E detection. Conclusion: ALX148 generates false‐positive reactivity in IAT, interfering with pretransfusion compatibility testing. The use of soluble CD47 or high‐affinity SIRPα monomers can resolve the interference without possibly missing clinically significant alloantibodies. [ABSTRACT FROM AUTHOR]

Cognition is a complex set of processes, including attention, learning and memory, that refers to the capacity to encode, consolidate, store and retrieve recent and remotely stored fact (semantic) and experience-based (episodic) memory. The development of cognitive enhancers is of particular importance to society and the pharmaceutical industry, as cognitive dysfunctions are observed across a wide range of neuropsychiatric and neurodegenerative disorders; however, developing such therapeutics has proven difficult. There is poor congruency between the abundance of positive results observed in animal studies compared with clinical outcome. For example, from 1982 to 2002 there was a 6000% increase in studies on cognitive processing in rodents that had little or no impact on the outcome of phase II and III clinical trials. The effects of therapeutics on models of cognition that demonstrate the potential to improve preclinical-to-clinical congruency, focusing on attention, impulsivity and episodic memory, are summarized in this review. Changes in attention, impulsivity and episodic memory are tractable 'disease biomarkers' that correlate with the disease phenotypes that are potential therapeutic targets. In the context of the development of cognitive enhancing drugs, one of the major goals of translational medicine is to improve the congruency between preclinical models and clinical results. Improved translatability could improve discovery, validation and implementation of biomarkers to inform clinical outcome studies and decision making, and to establish proof-of-concept for efficacy and safety based on targeted mechanisms of action.