Erythropoietin (EPO) is both hematopoietic and tissue protective, putatively through interaction with different receptors. We generated receptor subtype-selective ligands allowing the separation of EPO's bioactivities at the cellular level and in animals. Carbamylated EPO (CEPO) or certain EPO mutants did not bind to the classical EPO receptor (EPOR) and did not show any hematopoietic activity in human cell signaling assays or upon chronic dosing in different animal species. Nevertheless, CEPO and various nonhematopoietic mutants were cytoprotective in vitro and conferred neuroprotection against stroke, spinal cord compression, diabetic neuropathy, and experimental autoimmune encephalomyelitis at a potency and efficacy comparable to EPO.

3D printed PDMS (a) bridges at different exposure times, (b) fluidic device with a cross section of 500×500 μm 2 , and (c) blue and yellow dye flowing through the channels of the device in (b). 157 Reproduced from Desktop-Stereolithography 3D-Printing of a Poly(dimethylsiloxane)-Based Material with Sylgard-184 Properties, Bhattacharjee, N.;

No abstract

Copy-number variations (CNVs) are strong risk factors for neurodevelopmental and psychiatric disorders. The 15q13.3 microdeletion syndrome region contains up to ten genes and is associated with numerous conditions, including autism spectrum disorder (ASD), epilepsy, schizophrenia, and intellectual disability; however, the mechanisms underlying the pathogenesis of 15q13.3 microdeletion syndrome remain unknown. We combined whole-genome sequencing, human brain gene expression (proteome and transcriptome), and a mouse model with a syntenic heterozygous deletion (Df(h15q13)/+ mice) and determined that the microdeletion results in abnormal development of cortical dendritic spines and dendrite outgrowth. Analysis of large-scale genomic, transcriptomic, and proteomic data identified OTUD7A as a critical gene for brain function. OTUD7A was found to localize to dendritic and spine compartments in cortical neurons, and its reduced levels in Df(h15q13)/+ cortical neurons contributed to the dendritic spine and dendrite outgrowth deficits. Our results reveal OTUD7A as a major regulatory gene for 15q13.3 microdeletion syndrome phenotypes that contribute to the disease mechanism through abnormal cortical neuron morphological development.

This study evaluates the applicability of the liquid handling workstation Tecan Evo Freedom 200 and 200 lL Media Scout RoboColumns to dynamic chromatographic operations such as frontal analysis (breakthrough) and elution experiments in a high throughput screening mode. Breakthrough experiments were conducted using BSA as a model protein and the stationary phases Poros 50 D, Q Ceramic HyperD and DEAE Sepharose FF. The obtained dynamic capacities at 10 and 50 % breakthrough matched well with reference data. Elution experiments were performed applying three protein mixtures: a) lipolase and BSA, b) human growth hormone and a process-related impurity, and c) an insulin analogue and a process-related impurity. The resins used resembled a variety of different ion exchange resins. In all cases, the resulting elution curves matched well with reference measurements performed on an ÄKTA explorer system at 1 mL or 2 mL scale.