C9orf72-ALS human iPSC microglia are pro-inflammatory and toxic to co-cultured motor neurons via MMP9

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive motor neuron loss, with additional pathophysiological involvement of non-neuronal cells such as microglia. The commonest ALS-associated genetic variant is a hexanucleotide repeat expansion (HRE) mutation in C9orf72. Here, we study its consequences for microglial function using human iPSC-derived microglia. By RNA-sequencing, we identify enrichment of pathways associated with immune cell activation and cyto-/chemokines in C9orf72 HRE mutant microglia versus healthy controls, most prominently after LPS priming. Specifically, LPS-primed C9orf72 HRE mutant microglia show consistently increased expression and release of matrix metalloproteinase-9 (MMP9). LPS-primed C9orf72 HRE mutant microglia are toxic to co-cultured healthy motor neurons, which is ameliorated by concomitant application of an MMP9 inhibitor. Finally, we identify release of dipeptidyl peptidase-4 (DPP4) as a marker for MMP9-dependent microglial dysregulation in co-culture. These results demonstrate cellular dysfunction of C9orf72 HRE mutant microglia, and a non-cell-autonomous role in driving C9orf72-ALS pathophysiology in motor neurons through MMP9 signaling

Influence of reaction time and synthesis temperature on the physical properties of ZnO nanoparticles synthesized by the hydrothermal method

Influence of synthesis temperature and reaction time on the structural and optical properties of ZnO nanoparticles synthesized by the hydrothermal method was investigated using X-ray diffraction (XRD), high resolution transmission electron microscopy (HR-TEM), energy-dispersive X-ray, Fourier transform infra-red spectroscopy, and UV–visible and fluorescence spectroscopy. The XRD pattern and HR-TEM images confirmed the presence of crystalline hexagonal wurtzite ZnO nanoparticles with average crystallite size in the range 30–40 nm. Their energy gap determined by fluorescence was found to depend on the synthesis temperature and reaction time with values in the range 2.90–3.78 eV. Thermal analysis, thermogravimetric and the differential scanning calorimetry were used to study the thermal reactions and weight loss with heat of the prepared ZnO nanoparticles

ThermoMechanical Characterization of Calotropis gigantea

Filler performs key tasks in enhancing the strength of the composites. Calotropis gigantea is a weed waste typically called White Madar, widely grown in Asian countries. It is ground to powder and used as filler. Thus the present work deals with the development of three different jute fiber reinforced epoxy composite filled without and with various weight proportion of Calotropis gigantea stem powder namely 5 and 10 weight percentage using conventional hand lay-up technique. The developed composites are tested for its mechanical properties as per ASTM standards and thermal stability using the Thermo Gravimetric Analyzer. The composite which is filled with 10 weight percentage Calotropis gigantea powder filler showed superior properties in both thermal and mechanical characteristics due to its higher filler content which possess constituents like cellulose, lignin, etc. Scanning Electron Microscopy helped to analyze the fiber pullout, fractured interface, filler distribution, voids of the composites

C9orf72-ALS human iPSC microglia are pro-inflammatory and toxic to co-cultured motor neurons via MMP9

Abstract Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive motor neuron loss, with additional pathophysiological involvement of non-neuronal cells such as microglia. The commonest ALS-associated genetic variant is a hexanucleotide repeat expansion (HRE) mutation in C9orf72. Here, we study its consequences for microglial function using human iPSC-derived microglia. By RNA-sequencing, we identify enrichment of pathways associated with immune cell activation and cyto-/chemokines in C9orf72 HRE mutant microglia versus healthy controls, most prominently after LPS priming. Specifically, LPS-primed C9orf72 HRE mutant microglia show consistently increased expression and release of matrix metalloproteinase-9 (MMP9). LPS-primed C9orf72 HRE mutant microglia are toxic to co-cultured healthy motor neurons, which is ameliorated by concomitant application of an MMP9 inhibitor. Finally, we identify release of dipeptidyl peptidase-4 (DPP4) as a marker for MMP9-dependent microglial dysregulation in co-culture. These results demonstrate cellular dysfunction of C9orf72 HRE mutant microglia, and a non-cell-autonomous role in driving C9orf72-ALS pathophysiology in motor neurons through MMP9 signaling