Summary
Phagocytosis is required for a broad range of physiological functions, from pathogen defense to tissue homeostasis, but mechanisms required for phagocytosis of diverse substrates remain incompletely understood. Here, we develop a rapid magnet-based phenotypic screening strategy, and perform eight genome-wide CRISPR screens in human cells to identify genes regulating phagocytosis of distinct substrates. After validating select hits in focused mini-screens, orthogonal assays and primary human macrophages, we demonstrate that 1) the previously-uncharacterized gene NHLRC2 is a central player in phagocytosis, regulating RhoA-Rac1 signaling cascades that control actin polymerization and filopodia formation, 2) very long chain fatty acids are essential for efficient phagocytosis of certain substrates, and 3) the previously-uncharacterized Alzheimer’s disease-associated gene TM2D3 can preferentially influence uptake of amyloid-β aggregates. These findings illuminate new regulators and core principles of phagocytosis, and more generally establish an efficient method for unbiased identification of cellular uptake mechanisms across diverse physiological and pathological contexts.
Composite phases have been shown to improve both the thermoelectric efficiency and mechanical properties of materials. Here, we demonstrate an improved thermoelectric figure of merit, power factor, and mechanical properties for the high-temperature p-type Zintl phase Yb 14 MgSb 11 . Composites with 0, 1, 2, 3, 4, 6, and 8 vol % 6−10 μm reduced Fe powder were prepared via a fast, scalable, mechanical milling and spark plasma sintering procedure. Powder X-ray diffraction, scanning electron microscopy, and transmission electron microscopy show that Fe is not incorporated into the Yb 14 MgSb 11 structure. First-order reversal curves and scanning electron microscopy images show that the Fe inclusions are larger and closer together with increasing Fe content. Thermogravimetric and differential scanning calorimetry show that the composites are stable up to 1273 K. The elastic constants of the 8 vol % Fe composite were measured by resonant ultrasound spectroscopy and show that Yb 14 MgSb 11 becomes stiffer with increasing Fe volume % and SEM after indentations show crack arresting occurs at the Fe interface. Thermoelectric properties on dense pellets are measured from 300 K − 1273 K. The thermoelectric power factor (PF = S 2 /ρ) increases with increasing Fe content, with the 8 vol % Fe resulting in 40% higher PF than pristine Yb 14 MgSb 11 . The increase in PF is attributed to a systematic reduction in electrical resistivity. Peak thermoelectric figure of merit [zT = (S 2 T)/(κρ)] is observed at 3 vol % Fe, an 11% improvement in zT compared to Yb 14 MgSb 11 . Yb 14 MgSb 11 composites with Fe are compatible with Ce 0.9 Fe 3.5 Co 0.5 Sb 12 for thermoelectric generator couple segmentation. KEYWORDS: composite, thermoelectric, transport properties, Zintl phase, SPS synthesis, first-order reversal curves PFS 2
=ρ by band structure engineering, such as band convergence, tuning the electronic states with resonance levels, or simple substitutional alloying. There has also been significant research
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