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Purpose: Craniofacial microsomia (CFM) represents a spectrum of craniofacial malformations, ranging from isolated microtia with or without aural atresia to underdevelopment of the mandible, maxilla, orbit, facial soft tissue, and/or facial nerve. The genetic causes of CFM remain largely unknown., Methods: We performed genome sequencing and linkage analysis in patients and families with microtia and CFM of unknown genetic etiology. The functional consequences of damaging missense variants were evaluated through expression of wild-type and mutant proteins in vitro., Results: We studied a 5-generation kindred with microtia, identifying a missense variant in FOXI3 (p.Arg236Trp) as the cause of disease (logarithm of the odds = 3.33). We subsequently identified 6 individuals from 3 additional kindreds with microtia-CFM spectrum phenotypes harboring damaging variants in FOXI3, a regulator of ectodermal and neural crest development. Missense variants in the nuclear localization sequence were identified in cases with isolated microtia with aural atresia and found to affect subcellular localization of FOXI3. Loss of function variants were found in patients with microtia and mandibular hypoplasia (CFM), suggesting dosage sensitivity of FOXI3., Conclusion: Damaging variants in FOXI3 are the second most frequent genetic cause of CFM, causing 1% of all cases, including 13% of familial cases in our cohort., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

This work offers a facile fabrication method for lignin nanocomposites through the assembly of kraft lignin onto magnetic nanoparticles (Fe 3 O 4 ) based on pH-driven precipitation, without needing organic solvents or lignin functionalization. Kraft lignin@Fe 3 O 4 multicore nanocomposites fabrication proceeded using a simple, pH-driven precipitation technique. An alkaline solution for kraft lignin (pH 12) was rapidly injected into an aqueous-based Fe 3 O 4 nanoparticle colloidal suspension (pH 7) under constant mixing conditions, allowing the fabrication of lignin magnetic nanocomposites. The effects of increasing lignin to initial Fe 3 O 4 mass content (g/g), increasing in ratio from 1:1 to 20:1, are discussed with a complete chemical, structural, and morphological characterization. Results showed that nanocomposites fabricated above 5:1 lignin:Fe 3 O 4 had the highest lignin coverage and content (>20%), possessed superparamagnetic properties (Ms ≈ 45,000 A·m 2 /kg 2 ); had a negative surface charge (-30 mV), and formed multicore nanostructures (D H ≈ 150 nm). The multicore lignin@Fe 3 O 4 nanocomposites allowed rapid magnetically induced separations from suspension. After 5 min exposure to a rare-earth neodymium magnet (1.27 mm × 1.27 mm × 5.08 mm), lignin@Fe 3 O 4 nanocomposites exhibited a maximum methylene blue removal efficiency of 74.1% ± 7.1%. These nanocomposites have potential in magnetically induced separations to remove organic dyes, heavy metals, or other lignin adsorbates., Competing Interests: Declaration of competing interest None., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: In the second trimester of human fetal development, a tenfold increase in fetal size occurs while cardiac valves grow and retain their function. Patterns of transcription in normally growing human aortic valves are unknown., Methods: Discarded human aortic valve samples were collected from the second trimester, 6 from early (14, 15, 17 weeks) and 6 from late (20, 21, 22 weeks) gestation. Network analysis of RNA sequencing data identified subnetworks of significantly increasing and decreasing transcripts. Subsequent cluster analysis identified patterns of transcription through the time course. Pathway enrichment analysis determined the predominant biological processes at each interval., Results: We observed phasic transcription over the time course, including an early decrease in cell proliferation and developmental genes (14 to 15 weeks). Pattern specification, shear stress, and adaptive immune genes were induced early. Cell adhesion genes were increased from 14 to 20 weeks. A phase involving cell differentiation and apoptosis (17 to 20 weeks) was followed by downregulation of endothelial-to-mesenchymal transformation genes and then by increased extracellular matrix organization and stabilization (20 to 22 weeks)., Conclusions: We present a unique data set, comprehensively characterizing human valve development after valve primordia are formed, focusing on key processes displayed by normal aortic valves undergoing significant growth. We build a time course of genes and processes in second trimester fetal valve growth and observe the sequential regulation of gene clusters over time. Critical valve growth genes are potential targets for therapeutic intervention in congenital heart disease and have implications for regenerative medicine and tissue engineering., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Patterned SiGe thin film structures, heteroepitaxially deposited on Si substrates, are investigated as potential reference standards to establish the accuracy of high resolution electron backscattered diffraction (HR-EBSD) strain measurement methods. The proposed standards incorporate thin films of tetragonally distorted epitaxial Si₁-xGex adjacent to strain-free Si. Six films of three different nominal compositions (x=0.2, 0.3, and 0.4) and various thicknesses were studied. Film composition and out-of-plane lattice spacing measurements, by x-ray photoelectron spectroscopy and x-ray diffraction, respectively, provided independent determinations of film epitaxy and predictions of tetragonal strain for direct comparison with HR-EBSD strain measurements. Films assessed to be coherent with the substrate exhibited tetragonal strain values measured by HR-EBSD identical to those predicted from the composition and x-ray diffraction measurements, within experimental relative uncertainties of order 2%. Such films thus provide suitable prototypes for designing a strain reference standard., (Published by Elsevier B.V.)

Despite the fact that nanomaterials are considered potentially hazardous in a freely dispersed form, they are often considered safe when encapsulated into a polymer matrix. However, systematic research to confirm the abovementioned paradigm is lacking. Our data indicates that there are possible mechanisms of nanomaterial release from nanocomposites due to exposure to environmental conditions, especially UV radiation. The degradation of the polymer matrix and potential release of nanomaterials depend on the nature of the nanofillers and the polymer matrix, as well as on the nature of environmental exposure, such as the combination of UV, moisture, mechanical stress and other factors. To the best of our knowledge there is no systematic study that addresses all these effects. We present here an initial study of the stability of nanocomposites exposed to environmental conditions, where carbon nanotube (CNT) containing polymer composites were evaluated with various spectroscopic and microscopic techniques. This work discusses various degradation mechanisms of CNT polymer nanocomposites, including such factors as UV, moisture and mechanical damage. An in vivo ingestion study with Drosophila showed reduced survivorship at each dose tested with free amine-functionalized CNTs, while there was no toxicity when these CNTs were embedded in epoxy. In addition to developing new paradigms in terms of safety of nanocomposites, the outcomes of this research can lead to recommendations on safer design strategies for the next generation of CNT-containing products., (Copyright © 2013 Elsevier B.V. All rights reserved.)