Publications by authors named "Anthony J Asmar"

To facilitate the characterization of unlabeled induced pluripotent stem cells (iPSCs) during culture and expansion, we developed an AI pipeline for nuclear segmentation and mitosis detection from phase contrast images of individual cells within iPSC colonies. The analysis uses a 2D convolutional neural network (U-Net) plus a 3D U-Net applied on time lapse images to detect and segment nuclei, mitotic events, and daughter nuclei to enable tracking of large numbers of individual cells over long times in culture. The analysis uses fluorescence data to train models for segmenting nuclei in phase contrast images.

View Article and Find Full Text PDF
Article Synopsis
  • Researchers investigated the mechanisms that guide the differentiation of embryonic ectoderm into various structures like the nervous system and skin, focusing on the role of the CRL3-KLHL4 ubiquitin ligase.
  • This ligase regulates the signaling of the signaling molecule CDC42 by modifying the protein PAK1 through a process called monoubiquitylation, which unexpectedly turns PAK1 from a promoter of CDC42 activity into an inhibitor.
  • Disruption of this regulatory pathway, either by the loss of CRL3-KLHL4 or through genetic variants associated with disease, leads to excessive CDC42 activation, which interferes with proper ectodermal patterning and development of facial, brain, and skin structures.
View Article and Find Full Text PDF

Reversible modification of proteins with linkage-specific ubiquitin chains is critical for intracellular signaling. Information on physiological roles and underlying mechanisms of particular ubiquitin linkages during human development are limited. Here, relying on genomic constraint scores, we identify 10 patients with multiple congenital anomalies caused by hemizygous variants in , encoding a K48/K63 linkage-specific deubiquitylase.

View Article and Find Full Text PDF
Article Synopsis
  • Adult-onset inflammatory syndromes can exhibit overlapping symptoms, and the study discovered that mutations in ubiquitin-related genes, particularly in UBA1, are linked to these disorders.
  • Researchers utilized various methodologies, including exome sequencing and CRISPR technology, to identify mutations in patients with severe inflammatory conditions that typically develop in late adulthood.
  • The findings indicate that these mutations lead to a significant change in immune response and could help define a new inflammatory disorder related to genetic abnormalities in UBA1.
View Article and Find Full Text PDF

Metazoan development relies on intricate cell differentiation, communication, and migration pathways, which ensure proper formation of specialized cell types, tissues, and organs. These pathways are crucially controlled by ubiquitylation, a reversible post-translational modification that regulates the stability, activity, localization, or interaction landscape of substrate proteins. Specificity of ubiquitylation is ensured by E3 ligases, which bind substrates and co-operate with E1 and E2 enzymes to mediate ubiquitin transfer.

View Article and Find Full Text PDF

Cells are often subjected to the effect of reactive oxygen species (ROS) as a result of both intracellular metabolism and exposure to exogenous factors. ROS-dependent oxidative stress can induce 8-oxodG within the GGG triplet found in the G-rich human telomeric sequence (TTAGGG), making telomeres highly susceptible to ROS-induced oxidative damage. Telomeres are nucleoprotein complexes that protect the ends of linear chromosomes and their dysfunction is believed to affect a wide range of cellular and/or organismal processes.

View Article and Find Full Text PDF

Electromanipulation of cells as a label-free cell manipulation and characterization tool has gained particular interest recently. However, the applicability of electromanipulation, particularly dielectrophoresis (DEP), to biological cells is limited to cells suspended in buffers containing lower amounts of salts relative to the physiological buffers. One might question the use of low conductivity buffers (LCBs) for DEP separation, as cells are stressed in buffers lacking physiological levels of salt.

View Article and Find Full Text PDF